Effective Interventions in Restoring Mobility and Relieving Pain After Lower Limb Amputation

Suyeon (Su) Kim¹, Grace Kim¹, Dominick Shoha¹, Marcel P. Fraix², and Devendra K. Agrawal^1*

¹Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766, USA

²Department of Physical Medicine and Rehabilitation, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766, USA

^* Corresponding Author: Devendra K. Agrawal, Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766, USA.

Received: 25 August 2026; Accepted: 01 September 2026; Published: 07 September 2026

1. Introduction

Amputation may involve the upper or lower limb, and both forms can substantially affect independence, psychological well-being, social participation, and quality of life. As of 2017, more than 57 million people worldwide were estimated to be living with limb loss, and in the United States alone, approximately 185,000 amputations are performed each year [1,2]. Nearly 80% of these procedures are related to vascular disease and diabetes, while about 16% result from traumatic injury [3,4]. Furthermore, a 2023 global meta-analysis reported that among individuals with diabetes, the annual incidence of lower-limb amputation ranges from 95 to 140 per 100,000 people [5-10]. Collectively, these findings highlight limb loss as a significant public health concern with substantial consequences for mobility, independence, and quality of life.

Upper-limb amputation primarily compromises reach, grasp, bimanual activities, self-care, work, and community participation, whereas lower-limb amputation most directly restricts standing, transfers, gait, balance, endurance, and community mobility [11,12]. Because the evidence synthesized in this review predominantly concerns lower-limb loss, the discussion that follows focuses on lower-limb amputation while recognizing the distinct functional burden of upper-limb amputation.

The diverse etiologies of limb loss underscore the complexity of addressing patients’ clinical, rehabilitative, and psychosocial needs. While there have been advances in surgical techniques, prosthetic technology, and rehabilitative care, many amputees continue to endure functional limitations such as impaired gait and compromised balance, which may hinder return to work and community engagement [13,14]. Post-amputation pain remains highly prevalent. Phantom limb pain, residual limb pain, and secondary musculoskeletal strain, particularly in the lower back, can significantly impede recovery and contribute to emotional distress, including depression and anxiety [15-20]. In response to these challenges, healthcare providers employ a range of interventions designed to restore function and manage pain. Rehabilitative approaches such as mirror therapy and mirror visual feedback have demonstrated reductions in phantom limb pain severity [21]. Additionally, pharmacological agents, including gabapentin, morphine, and ketamine, offer short-term symptom relief [22-24]. Regional analgesic strategies, such as peripheral nerve blocks and epidural analgesia, have been shown to reduce postoperative pain and support functional gains [25-30]. Additionally, emerging innovations, including targeted muscle reinnervation and advanced prosthetic control systems, have shown promise in improving neuromuscular coordination and enabling more natural limb function [31,32].

This comprehensive literature review synthesizes current evidence on functional rehabilitation and pain management following limb amputation, highlighting established practices, ongoing debates, and key gaps. By examining established practices, emerging innovations, and persistent knowledge gaps, this work aims to identify the strategies that most effectively promote recovery, optimize long-term outcomes, and advance integrated, patient-centered approaches to care for individuals with amputations.

2. Impact on Mobility

2.1 Primary Mobility Limitations

Lower-limb amputation is associated with significant and often persistent functional limitations that affect mobility, gait, balance, and the ability to perform daily activities [33,34]. While some difficulties are temporary and arise during the immediate postoperative recovery period, many individuals face long-term challenges that persist well beyond the initial rehabilitation phase [35,36]. These limitations can significantly influence independence and overall quality of life, even in the context of modern surgical techniques, advanced prosthetic technologies, and structured rehabilitation programs.

Among all functional domains, mobility loss is among the most substantial. Limb loss disrupts normal biomechanics, resulting in slower walking speeds, asymmetrical gait, and increased energy expenditure during ambulation [37]. Amputees often have trouble climbing stairs, walking on uneven terrain, and performing transitional movements such as turning or sit-to-stand [38]. Mobility challenges are particularly prominent among individuals with dysvascular lower-limb amputations [39]. Lee et al. [40] state that only about half of these individuals utilize walking as their primary mode of mobility one year after amputation, indicating substantial physical and adaptive demands of gait restoration. Reduced ambulatory capacity may lead to increased reliance on assistive devices, decreased physical activity, and heightened risk of secondary complications, including deconditioning and joint pain [41].

Balance and endurance are also frequently compromised following lower-limb loss. The absence of proprioceptive feedback and altered weight distribution increase postural instability and the risk of falls [42]. Decreased confidence in balance can perpetuate inactivity and reduced cardiovascular endurance [43]. Lower-limb amputees often demonstrate shorter walking distances and reduced exercise tolerance compared to able-bodied individuals [44]. Unfortunately, even with modern prosthetic designs, consequences such as fatigue, socket discomfort, and high energy expenditure limit the long-term use of prosthetics and independent ambulation [45,46].

Additionally, functional limitations may negatively impact a patient’s occupational and social domains. The time to return to work can often be prolonged due to reduced ability to stand, walk, and perform job-related physical tasks, which creates challenges. Evidence indicates that fewer than one in three individuals with dysvascular lower-limb amputation successfully return to employment [40]. Beyond work productivity, limited mobility and prosthetic discomfort may restrict participation in community activities, hinder social engagement, and contribute to psychological distress such as anxiety, depression, and reduced self-efficacy [47].

2.2 Early Mobility Loss Following Lower-Limb Amputation

In a Danish prospective cohort study, Madsen et al. [48] examined short-term functional outcomes following dysvascular lower-limb amputation using the Barthel Index (BI) to measure changes in activities of daily living (ADL) from pre-amputation to Day 21 post-surgery, reporting a significant decline across all ten BI domains [48]. These domains included personal hygiene, bathing, eating, toileting, dressing, bowel and bladder control, ambulation or wheelchair use (if non-ambulatory), bed-chair transfers, and stair climbing [49]. The study identified older age (≥ 65 years), higher ASA score, and lack of prosthesis assessment before discharge as significant predictors of continued dependence [50]. Similarly, in Italy, Brunelli et al. [51] evaluated 135 post-amputation patients and found that although BI scores improved during rehabilitation, the tool underestimated mobility changes, those related to transfers and prosthetic adaptation [51]. Elevated plasma homocysteine (H-HCY), a marker of vascular disease, was significantly associated with lower rehabilitation effectiveness, emphasizing how metabolic and comorbid factors influence early recovery. Complementing these findings, Venkataraman et al. [52] analyzed rehabilitation outcomes among U.S. inpatients with dysvascular amputations and reported that early initiation of rehabilitation (within 7 days) led to significantly higher Functional Independence Measure (FIM) scores and greater discharge mobility compared to delayed therapy, even after adjusting for age, amputation level, and comorbidities [52]. Taken together, these studies demonstrate that early functional decline after amputation is profound and consistent across populations, but recovery potential is strongly influenced by both non-modifiable factors (age, baseline health, vascular/metabolic status) and modifiable factors (timing of rehabilitation, prosthesis evaluation, and individualized discharge planning). Collectively, this evidence underscores the importance of early, multidisciplinary rehabilitation interventions to mitigate immediate postoperative dependence and optimize mobility within the first month after surgery.

2.3 Transtibial Versus Transfemoral Amputation: Recovery, Prosthetics, and Rehabilitation

The distinction between transtibial and transfemoral amputation is clinically important because preservation of the knee joint changes the expected rehabilitation course, prosthetic prescription, gait demands, and likelihood of independent ambulation. Transtibial rehabilitation generally emphasizes residual limb management, prosthetic alignment, ankle-foot substitution, balance, and gait symmetry. Transfemoral rehabilitation additionally requires mastery of a prosthetic knee, greater hip strength and trunk control, more intensive fall prevention training, and accommodation of higher metabolic demands during walking [53,54].

The level of amputation is one of the most critical determinants of long-term functional outcomes. Evidence consistently shows that higher (more proximal) levels of amputation are associated with greater mobility limitations and reduced independence. In a large-scale systematic review and meta-analysis, Penn-Barwell et al. [55] demonstrated that patients with below-knee amputations (BKA) retained superior mobility compared to those with above-knee amputations (AKA) or bilateral limb loss, exhibiting greater ambulatory capacity and functional independence. These findings have been corroborated by subsequent clinical and observational studies. For instance, Kaur et al. [56] reported that individuals with BKA exhibited more symmetrical gait patterns, higher average walking speeds, and longer daily prosthesis use relative to those with AKA [56]. Similarly, Seker et al. [57] found significantly higher Amputee Mobility Predictor (AMP) scores among transtibial amputees, both with and without prostheses, suggesting better overall functional mobility [57]. These advantages are largely attributed to the preservation of the knee joint, which enables more natural limb mechanics, improved prosthetic control, and lower energy expenditure during ambulation [58,59].

In contrast, individuals with transfemoral amputations face more profound biomechanical limitations. The absence of the knee joint precludes active plantar flexion and push-off during gait, forcing patients to rely primarily on hip musculature for forward propulsion [60]. This compensatory mechanism increases energy consumption and reduces gait efficiency [61,62]. Such adaptations contribute to slower walking speeds, greater gait asymmetry, and higher physical demands during daily activities such as transfers and stair climbing. During sit-to-stand maneuvers, individuals with lower-limb amputations (LLA) tend to lean toward the intact limb, resulting in greater load and higher knee joint moments on that side [60]. Over time, this preferential loading contributes to the development of contralateral knee osteoarthritis, particularly among individuals with AKA [63]. These mechanical and metabolic inefficiencies collectively reduce endurance, functional participation, and overall quality of life.

Beyond physical impairment, amputation also imposes enduring barriers to employment and social reintegration. Reduced walking endurance, prosthetic discomfort, and secondary musculoskeletal conditions limit activity participation, while psychological distress—including depression, anxiety, and altered self-identity, further impairs rehabilitation outcomes [64]. The AHA emphasizes that consistent prosthesis use and walking ability are among the strongest predictors of quality of life and social participation following amputation [65]. To enhance these outcomes, the AHA recommends integrated behavioral health interventions during rehabilitation to facilitate psychosocial adjustment and promote community reintegration.

Physical performance measures such as the Timed Up and Go (TUG) test and self-reported mobility ratings are positively correlated with re-employment and social participation among amputees [66,67]. Conversely, persistent pain, prosthetic dissatisfaction, and limited prosthesis use are negatively associated with return-to-work outcomes [68-70]. The U.S. Department of Veterans Affairs and Department of Defense (VA/DoD) clinical practice guideline advises comprehensive rehabilitation that includes pain management, psychosocial screening, and standardized mobility assessments to mitigate these barriers and improve long-term outcomes [71,72]. Despite these recommendations, recent studies indicate that fewer than one-third of dysvascular amputees successfully return to work, with earlier data reporting re-employment rates of approximately 40% [40]. These findings underscore that successful reintegration after amputation depends not only on physical capacity but also on psychological resilience and environmental support. Thus, optimizing both functional rehabilitation and psychosocial interventions remains essential for restoring autonomy and improving quality of life in this population.

2.4 Determinants of Functional Recovery

Psychological and behavioral factors exert a profound influence on post-amputation recovery, shaping both functional outcomes and pain perception [73,74]. Motivation, self-efficacy, and coping style influence not only engagement in rehabilitation but also tolerance of discomfort, adaptation to prosthetic use, and sustained long-term mobility [74,75]. Individuals who approach rehabilitation with optimism and problem-solving behaviors tend to regain higher levels of independence, whereas maladaptive responses such as catastrophizing and avoidance often perpetuate pain, prosthesis abandonment, and functional decline [76]. Cognitive-behavioral therapy (CBT), motivational interviewing, and peer mentoring have each shown promise in enhancing self-efficacy and fostering active engagement in therapy [77-80]. Furthermore, virtual and augmented reality interventions are emerging as tools to promote body schema restoration, improve adherence to mirror therapy, and reduce phantom limb pain [81-83]. Targeting psychological barriers early in rehabilitation fosters resilience, a biopsychosocial multiplier that accelerates recovery, optimizes prosthetic adaptation, and sustains meaningful participation in daily life.

Beyond the psychological domain, surgical and anatomical factors lay the physiological foundation for functional recovery. Advances in operative techniques, including Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interfaces (RPNI), have significantly reduced neuroma-related pain and enhanced the control of myoelectric prostheses [84-88]. Likewise, meticulous attention to muscle reattachment, bone length preservation, and limb contouring during amputation improves prosthetic suspension and load distribution, thereby facilitating smoother gait mechanics and endurance [12,89,90]. Emerging methods, such as osseointegration, direct skeletal anchoring of the prosthesis, restore proprioceptive feedback and reduce energy expenditure, offering a more natural and stable interface between the body and device [91-93]. In this context, a function-oriented surgical approach that anticipates prosthetic integration becomes a pivotal determinant of mobility and comfort, reinforcing that recovery begins in the operating room as much as in the rehabilitation clinic.

Functional recovery after amputation is not determined solely by clinical factors; socioeconomic and environmental contexts also play equally critical roles. Access to advanced prosthetic technologies, comprehensive rehabilitation services, and pain management interventions is often constrained by insurance coverage, geographic location, and the structure of the health system [94-97]. Individuals in rural or low-resource settings frequently experience delayed prosthetic fitting and limited follow-up care, resulting in poorer mobility and reduced participation [98-100]. Cross-national disparities further highlight how policy, infrastructure, and funding differences shape recovery trajectories, with higher-income countries demonstrating superior long-term outcomes compared to regions where prosthetic access remains scarce [101,102]. Social support and family involvement also strongly influence adaptation, motivation, and adherence to therapy, while cultural perceptions of disability can either foster empowerment or reinforce isolation [103-105]. Recognizing these social and environmental determinants is crucial to developing equitable rehabilitation models that bridge care gaps and promote functional independence across diverse populations.

3. Pain After Amputation

3.1 Types and Mechanisms of Post-Amputation Pain

Post-amputation pain (PAP) is a multifaceted clinical problem that significantly affects individuals following limb loss. It encompasses three major categories: phantom limb pain (PLP), residual limb pain (RLP), and secondary musculoskeletal pain. PLP refers to painful sensations perceived in the missing portion of the limb, often described as burning, stabbing, or cramping [106]. It is reported in up to 85% of amputees and can persist for years after surgery [107-109]. RLP, in contrast, arises from the stump tissues and is frequently linked to peripheral nerve injury, neuroma formation, ischemia, infection, or prosthetic pressure [110]. Secondary musculoskeletal pain develops due to compensatory movement patterns, joint overload, or spinal malalignment resulting from altered biomechanics [111]. Although these syndromes overlap clinically, differentiating among them is essential for accurate diagnosis and management.

The underlying mechanisms of post-amputation pain involve interacting peripheral, central, and psychosocial pathways. At the peripheral level, nerve transection leads to aberrant axonal sprouting and neuroma formation, producing ectopic discharges that amplify nociceptive input [112]. Persistent afferent firing contributes to spinal dorsal horn hyperexcitability and maladaptive neuroplasticity in supraspinal centers [113]. Functional neuroimaging studies have demonstrated that cortical reorganization within the somatosensory and motor cortices correlates with PLP intensity, implicating central sensitization and disrupted body schema. Psychological factors, including pain-related anxiety, catastrophizing, and pre-amputation pain memory, can further sustain central hyperexcitability. This biopsychosocial model underscores that post-amputation pain is not solely a peripheral phenomenon but a dynamic interplay between neural and cognitive processes.

3.2 Impact on Quality of Life and Rehabilitation Outcomes

Persistent pain after amputation exerts a profound impact on mobility, independence, and psychosocial well-being [114,115]. Chronic PAP often limits prosthetic tolerance, reduces walking speed, and increases energy expenditure during ambulation, leading to early fatigue and dependency on assistive devices [38,116,117]. Individuals with significant pain are less likely to achieve community ambulation or return to work, and they frequently experience greater disability scores and lower health-related quality of life indices [14-16,118]. In addition, compensatory overuse of the intact limb can result in contralateral joint degeneration and spinal discomfort, compounding overall morbidity [119,120].

Psychologically, uncontrolled pain contributes to sleep disturbance, depression, anxiety, and social isolation, all of which impede motivation for rehabilitation [121,122]. Pain-related fear and avoidance behaviors can delay prosthetic training and limit participation in therapy, leading to functional deconditioning [123-125]. The cumulative effect is a negative feedback loop in which pain reduces activity, inactivity exacerbates disability, and diminished function reinforces psychological distress [126]. Adequate pain control is therefore integral to restoring both physical function and emotional resilience, serving as a prerequisite for successful reintegration and long-term rehabilitation outcomes.

3.3 Current Pain Management Approaches

The management of post-amputation pain requires a multimodal and interdisciplinary strategy targeting both peripheral and central mechanisms. Pharmacologic therapies remain the first line of treatment, including anticonvulsants (gabapentin, pregabalin), antidepressants (tricyclics, SNRIs), NMDA receptor antagonists, and limited use of opioids for acute pain control [127-129]. Topical agents and local anesthetics may provide adjunctive relief for stump discomfort [130]. Surgical and interventional techniques—such as targeted muscle reinnervation (TMR), regenerative peripheral nerve interfaces (RPNI), and peripheral nerve capping- address neuroma-related pain by re-establishing physiological nerve targets [87,131,132]. Neuromodulation approaches, including spinal cord stimulation (SCS) and dorsal root ganglion (DRG) stimulation, have demonstrated efficacy for refractory PLP and RLP, particularly when conservative measures fail [133-135].

Non-pharmacologic modalities are increasingly emphasized to address central and psychosocial components. Mirror therapy, graded motor imagery, virtual reality training, and sensory discrimination therapy modulate cortical reorganization and restore body representation [136,137]. Cognitive-behavioral therapy (CBT) and mindfulness-based interventions mitigate catastrophizing and improve coping strategies [78-80,138]. Comprehensive rehabilitation programs integrating medical, psychological, and functional interventions achieve superior outcomes compared to unimodal treatments [139,140]. The evolving paradigm in post-amputation care emphasizes personalized, mechanism-informed, and multidisciplinary management to achieve durable pain relief and enhance overall function.

4. Emerging and Advanced Interventions

4.1 Technological Innovations in Prosthetics

Advances in prosthetic design have focused on closing the gap between human intention and device responsiveness. Microprocessor-controlled prostheses (such as knees and ankles) dynamically adjust resistance and deliver powered assistance during ambulation, enhancing cadence adaptability, reducing metabolic energy expenditure, and improving safety on varied terrains [141]. These devices have demonstrated meaningful improvements in gait symmetry, walking velocity, and fall reduction in clinical trials [142,143].

Osseointegration (OI) represents another transformative innovation, providing direct skeletal attachment of the prosthesis without the need for a socket [144]. This technique improves comfort, proprioception (“osseoperception”), and range of motion, while reducing soft-tissue irritation [145]. However, complications such as infection and periprosthetic fracture remain concerns requiring long-term surveillance [146,147].

Additionally, advanced neural control systems, including targeted muscle reinnervation (TMR), regenerative peripheral nerve interfaces (RPNIs), and pattern recognition myoelectric control, allow users to command multiple prosthetic degrees of freedom using natural motor signals [148]. Integration with sensory feedback systems (vibrotactile or electrotactile stimulation) enhances embodiment and postural stability [149]. Emerging socket technologies, utilizing additive manufacturing and embedded pressure sensors, further individualize fit and enhance residual limb health [150]. Collectively, these innovations demonstrate measurable functional and quality-of-life benefits but remain limited by device cost, maintenance demands, and training requirements.

4.2 Neuromodulation and Neurorehabilitation

Pain after amputation remains a significant barrier to recovery, with neuropathic and central sensitization mechanisms contributing to residual and phantom limb pain. Neuromodulatory interventions, including peripheral nerve stimulation (PNS), dorsal root ganglion (DRG) stimulation, and spinal cord stimulation (SCS), offer promising pain reduction for patients who are refractory to conventional therapies [151-153]. These techniques modulate abnormal nociceptive signaling, resulting in significant improvements in pain scores, sleep quality, and functional engagement [154-157].

Noninvasive brain stimulation methods, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), have demonstrated short-term analgesic effects and benefits in cortical remapping in small clinical trials [158-160]. Surgical neurorehabilitation strategies, including TMR and RPNI, also address neuroma pain while enhancing prosthetic control by reassigning severed nerves to new motor targets [84,87,161]. When integrated with task-specific therapy and graded motor imagery or mirror therapy, these approaches facilitate cortical normalization and reduce phantom limb phenomena [162-164].

Although early evidence suggests durable pain relief and functional gains, heterogeneity in patient selection and trial design limits the generalizability of these findings [165-167]. Ongoing multicenter trials aim to clarify optimal stimulation targets, protocols, and long-term cost-effectiveness [167-169].

4.3 Regenerative and Biologic Approaches

Regenerative medicine has introduced biologically based solutions to improve residual limb integrity and mitigate neuropathic complications [170,171]. Surgical nerve management techniques—particularly TMR and RPNI—are supported by growing clinical evidence demonstrating substantial reductions in neuroma and phantom limb pain, along with improved myoelectric control [84,172-175]. Complementary strategies include the use of nerve conduits, biologic wraps, and extracellular matrix (ECM) scaffolds to guide axonal regeneration and modulate local inflammation [176-180].

Additionally, autologous biologics, such as platelet-rich plasma (PRP) and fat grafting, are being investigated for restoring soft-tissue volume and reducing stump pain [181,182]. Within the context of osseointegration, bioactive surface coatings and antimicrobial modifications aim to enhance bone-implant integration and reduce the risk of infection [183-188]. While these regenerative modalities are conceptually promising, robust randomized trials and standardized outcome measures are needed to validate efficacy and safety [189-193].

4.4 Virtual and Augmented Reality Rehabilitation

Virtual reality and augmented reality (VR/AR) platforms are emerging as novel tools for motor retraining and pain modulation [81,194]. VR-based rehabilitation programs simulate variable environments to improve gait adaptability, balance, and confidence while providing quantitative kinematic feedback [194-196]. Embodiment-focused applications allow amputees to visualize a virtual limb responding to motor or EMG input, facilitating cortical reorganization and reducing phantom pain through visual-sensory coupling [197-199].

Augmented reality systems provide real-time visual overlays to guide prosthetic alignment, foot placement, and weight-shifting exercises, enabling telerehabilitation and improved home training compliance [200-202]. Moreover, gamified interfaces linked to prosthetic sensors promote high-repetition, task-specific movement practice, enhancing neuromuscular coordination [203-205].

Preliminary studies have reported significant short-term improvements in both pain and functional outcomes with VR/AR-based protocols compared to conventional therapy [194,206,207]. However, the scalability of these technologies is constrained by hardware costs, motion sickness in some users, and a lack of standardized implementation across clinical settings [203,208,209].

5. Challenges and Future Directions

Despite significant progress in prosthetic technology, neuromodulation, and regenerative medicine, multiple challenges continue to impede optimal recovery and equitable access to care for individuals with limb loss [95,129]. Disparities in access, inconsistent research standards, and limited long-term evidence hinder the translation of these advances into tangible benefits in the real world [94,129,210]. At the same time, emerging trends in personalized, data-driven rehabilitation and multidisciplinary collaboration offer promising directions for the future of amputation care.

Access to rehabilitation and prosthetic care remains highly unequal worldwide [211]. Individuals from low-income, uninsured, or rural populations frequently encounter delays in prosthetic fitting, limited availability of specialized rehabilitation centers, and inconsistent follow-up care [98,212,213]. These inequities lead to poorer functional recovery, increased secondary complications, and reduced quality of life [94,95,214]. Insurance and reimbursement restrictions further constrain access to advanced prosthetic systems, osseointegration procedures, and long-term physical therapy [215]. Addressing these barriers will require coordinated policy reform, community-based rehabilitation networks, and broader implementation of tele-rehabilitation programs to improve continuity of care and accessibility of expert services [216].

A second challenge lies in the lack of standardized, long-term data across studies assessing prosthetic outcomes and pain management interventions [174,202]. Many investigations remain short in duration, use heterogeneous metrics, and fail to employ uniform patient-reported outcome measures (PROMs) [190,217,218]. Without consistent reporting frameworks, it is difficult to compare findings, perform meta-analyses, or identify predictors of durable functional success [219]. Establishing internationally recognized registries and adopting consensus-based core outcome sets will be crucial for generating reproducible, high-quality evidence that informs both clinical practice and policy development [220-222].

Looking forward, integrating personalized, data-driven, and multidisciplinary care models represents a crucial step in advancing amputation rehabilitation [221,223]. Wearable sensors, digital gait analytics, and machine learning algorithms now provide continuous feedback on limb loading, prosthesis performance, and energy expenditure, enabling real-time, individualized therapy adjustments [224-227]. By combining biomechanical, neurological, and psychosocial data, clinicians may soon be able to predict complications, optimize device selection, and tailor pain management strategies for each patient [228-230]. A truly multidisciplinary model, uniting surgeons, physiatrists, prosthetists, therapists, and mental health specialists, will be critical to achieving holistic recovery that addresses both physical and psychosocial dimensions of adaptation [223,231,232].

Future research should prioritize the continued development of neuroprosthetics that enable intuitive, bidirectional communication between the nervous system and prosthetic devices, thereby improving motor control, sensory feedback, and embodiment [233-237]. Simultaneously, greater emphasis must be placed on psychosocial resilience, including strategies to enhance coping mechanisms, social reintegration, and long-term mental health after limb loss [238,239]. Finally, establishing standardized outcome measures and conducting multicenter, longitudinal trials will provide the robust evidence necessary to evaluate safety, cost-effectiveness, and long-term durability of new interventions [190,192,240,241].

6. Conclusion

Lower-limb amputation remains a life-altering condition that significantly impacts mobility, independence, and quality of life. Successful recovery is shaped by a complex combination of biomechanical, neurological, psychological, and socioeconomic factors. Functional outcomes depend not only on surgical technique and amputation level, but also on timely rehabilitation, access to prosthetics, and patient engagement. Post-amputation pain remains a major barrier to recovery, requiring a multidisciplinary mechanistic approach to management. Advances in surgical techniques, prosthetic technologies, and rehabilitation strategies offer promising improvements in function and pain control, but long-term effectiveness and accessibility remain limited. Persistent disparities in care highlight the need for more equitable access, standardized outcome measures, and long-term research. Ultimately, optimizing outcomes after amputation requires an integrated, patience-centered approach that addresses both physical and psychosocial dimensions of recovery.

Author contributions :

SK, DKA: contributed to the concept; SK, GK, DS: literature search, data extraction, analysis, and original draft preparation; MPF and DKA: advice, guidance, editing and resources.

Funding:

The research work of DKA is supported by the R25AI179582 grant from the National Institutes of Health, USA. The contents of this research article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

Competing interests :

All authors have read the manuscript and declare no relevant financial or non-financial interests. No writing assistance was utilized in the production of this manuscript.

Ethics approval :

Not applicable. This review used published literature and did not involve new human participant data.

Consent for publication :

All authors have read the manuscript and consented for publication.

References

1. McDonald CL, Westcott-McCoy S, Weaver MR, et al. Global prevalence of traumatic non-fatal limb amputation. Prosthet Orthot Int 45 (2021): 105-114.
2. Ziegler-Graham K, MacKenzie EJ, Ephraim PL, et al. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil 89 (2008): 422-429.
3. Walicka M, Raczyńska M, Marcinkowska K, et al. Amputations of Lower Limb in Subjects with Diabetes Mellitus: Reasons and 30-Day Mortality. J Diabetes Res 2021 (2021): 8866126.
4. Ishigami S, Boctor C. Epidemiology and risk factors for phantom limb pain. Front Pain Res 5 (2024).
5. Ezzatvar Y, García-Hermoso A. Global estimates of diabetes-related amputations incidence in 2010-2020: A systematic review and meta-analysis. Diabetes Res Clin Pract 195 (2023).
6. Rai V, Moellmer R, Agrawal DK. Stem Cells and Angiogenesis: Implications and Limitations in Enhancing Chronic Diabetic Foot Ulcer Healing. Cells 11 (2022): 2287.
7. Rai V, Le H, Agrawal DK. Novel mediators regulating angiogenesis in diabetic foot ulcer healing. Can J Physiol Pharmacol 101 (2023): 488-501.
8. Rai V, Moellmer R, Agrawal DK. Role of fibroblast plasticity and heterogeneity in modulating angiogenesis and healing in the diabetic foot ulcer. Mol Biol Rep 50 (2023): 1913-1929.
9. Rai V, Moellmer R, Agrawal DK. The role of CXCL8 in chronic nonhealing diabetic foot ulcers and phenotypic changes in fibroblasts: a molecular perspective. Mol Biol Rep 49 (2022): 1565-1572.
10. Littig JPB, Moellmer R, Estes AM, et al. Increased Population of CD40+ Fibroblasts Is Associated with Impaired Wound Healing and Chronic Inflammation in Diabetic Foot Ulcers. J Clin Med 11 (2022): 6335.
11. Fortington LV, Rommers GM, Geertzen JHB, et al. Mobility in elderly people with a lower limb amputation: a systematic review. J Am Med Dir Assoc 13 (2012): 319-325.
12. Krześniak NE, Hsu CC, Chen SH, et al. Exploring the Role of Free Tissue Transfers in the Preservation of Bone Length and Knee Joint Function after Lower Limb Trauma: A Retrospective Analysis. J Pers Med 14 (2024): 160.
13. Kanitkar A, Parmar ST, Szturm TJ, et al. Evaluation of a computer game-assisted rehabilitation program for manual dexterity of children with cerebral palsy: Feasibility randomized control trial. PM R 15 (2023): 1280-1291.
14. Karaali E, Duramaz A, Çiloğlu O, et al. Factors affecting activities of daily living, physical balance, and prosthesis adjustment in non-traumatic lower limb amputees. Turk J Phys Med Rehabil 66 (2020): 405-412.
15. Lower Limb Amputations: Epidemiology and Assessment. PM&R KnowledgeNow (2017).
16. Mall CP, Trivedi JK, Mishra US, et al. Psychiatric sequelae of amputation: I immediate effects. Indian J Psychiatry 39 (1997): 313-317.
17. Aabedi A, Wang V, Fraix MP, et al. Psychological Treatment in the Management of Pain following Musculoskeletal Injury. J Orthop Sports Med 7 (2025): 162-168.
18. McEntire DM, Kirkpatrick DR, Dueck NP, et al. Pain transduction: a pharmacologic perspective. Expert Rev Clin Pharmacol 9 (2016): 1069-1080.
19. Kirkpatrick DR, McEntire DM, Hambsch ZJ, et al. Therapeutic Basis of Clinical Pain Modulation. Clin Transl Sci 8 (2015): 848-856.
20. Supra R, Agrawal DK. Innate Immune Response in Orthopedic Implant Failure. J Orthop Sports Med 5 (2023): 9-19.
21. Tung ML, Murphy IC, Griffin SC, et al. Observation of limb movements reduces phantom limb pain in bilateral amputees. Ann Clin Transl Neurol 1 (2014): 633-638.
22. Finn SB, Perry BN, Clasing JE, et al. A Randomized, Controlled Trial of Mirror Therapy for Upper Extremity Phantom Limb Pain in Male Amputees. Front Neurol 8 (2017): 267.
23. Yarcan A, Abdou A, Agrawal DK. Perioperative Anxiety and Stress Cortisol on Postoperative Pain: Pharmacological and Non-Pharmacological Management Strategies. J Surg Res (Houst) 9 (2026): 165-175.
24. Aabedi A, Agrawal DK. Emerging Biologics in Lumbar Disc Degeneration: PRP, Stem Cell Therapy, and Pharmacotherapy in Mobility Restoration and Rehabilitation. J Spine Res Surg 8 (2026): 14-21.
25. Parvizi D, Kandikattu S, Sahafi R, et al. Multimodal Approaches for Pain Management and Improving Functional Outcomes Following Amputation. J Orthop Sports Med 7 (2025): 449-463.
26. Alviar MJM, Hale T, Dungca M. Pharmacologic interventions for treating phantom limb pain. Cochrane Database Syst Rev 10 (2016).
27. Kincaid S, How J, Agrawal DK. Multimodal Analgesia in the Perioperative Period of Major Surgeries: An In-depth Analysis. Anesth Crit Care 7 (2025): 68-76.
28. Cameron A, Fraix MP, Agrawal DK. Therapeutic Use of Medical Cannabis Beyond Pain Management in Physical Medicine and Rehabilitation. Arch Intern Med Res 10 (2026).
29. Dost A, Alaraj R, Mayet R, et al. Reshaping Anesthesia with Artificial Intelligence: From Concept to Reality. Anesth Crit Care 7 (2025): 77-90.
30. Aavula M, Parvizi D, Kandikattu S, et al. Integrating Mechanical Diagnosis and Therapy Within Multidisciplinary Biopsychosocial Care for Chronic Musculoskeletal Pain. J Orthop Sports Med 8 (2026): 49-57.
31. Ferris AE, Aldridge JM, Rábago CA, et al. Evaluation of a Powered Ankle-Foot Prosthetic System During Walking. Arch Phys Med Rehabil 93 (2012): 1911-1918.
32. Fagioli I, Mazzarini A, Livolsi C, et al. Advancements and Challenges in the Development of Robotic Lower Limb Prostheses: A Systematic Review. IEEE Trans Med Robot Bionics PP (2024): 1-1.
33. Mukkamala N, Vala S. Functional Mobility in Individuals With Lower Limb Amputation: An Observational Study. Cureus 16 (2024): 1-1.
34. Miller WC, Speechley M, Deathe AB. Balance confidence among people with lower-limb amputations. Phys Ther 82 (2002): 856-865.
35. Esfandiari E, Yavari A, Karimi A, et al. Long-term symptoms and function after war-related lower limb amputation: A national cross-sectional study. Acta Orthop Traumatol Turc 52 (2018): 348-351.
36. Bergman H, Clay B, Lane T. Long-term outcomes of major and minor lower limb amputation: eight-year retrospective analysis from a single tertiary referral centre. J Vasc Soc G B Irel 3 (2024).
37. Seth M, Coyle PC, Pohlig RT, et al. Gait asymmetry is associated with performance-based physical function among adults with lower-limb amputation. Physiother Theory Pract 38 (2022): 3108-3118.
38. Fischer G, Antunes D, Volpato A, et al. Metabolic Cost and Performance of Athletes With Lower Limb Amputation and Nonamputee Matched Controls During Running: A Systematic Review. Am J Phys Med Rehabil 101 (2022): 584-589.
39. Czerniecki JM, Turner AP, Williams RM, et al. Mobility Changes in Individuals With Dysvascular Amputation From the Presurgical Period to 12 Months Postamputation. Arch Phys Med Rehabil 93 (2012): 1766-1773.
40. Lee SP, Chien LC, Shih HT, et al. Returning to work after dysvascular lower limb amputation-A novel multivariate approach to examine relative contributions of biopsychosocial predictors. Prosthet Orthot Int 49 (2024): 30-37.
41. Functional capacity of elderly with lower-limb amputation after prosthesis rehabilitation: a longitudinal study. Disabil Rehabil Assist Technol 16 (2021): 1-1.
42. Miller W, Deathe A. A prospective study examining balance confidence among individuals with lower limb amputation. Disabil Rehabil 26 (2004): 875-881.
43. Tsang C, Leung J, Kwok T. Self-perceived balance confidence is independently associated with any subsequent falls and injurious falls among community-dwelling older fallers: A prospective cohort study. Arch Gerontol Geriatr 103 (2022): 104776.
44. Crouse SF, Lessard CS, Rhodes J, et al. Oxygen consumption and cardiac response of short-leg and long-leg prosthetic ambulation in a patient with bilateral above-knee amputation: comparisons with able-bodied men. Arch Phys Med Rehabil 71 (1990): 313-317.
45. JAAOS - Journal of the American Academy of Orthopaedic Surgeons. JAAOS (2019).
46. Aschoff HH, Juhnke DL. Evaluation of 10 years experience with endo-exo femur prostheses - background, data and results. Z Orthop Unfall 150 (2012): 607-614.
47. Williams RM, Ehde DM, Smith DG, et al. A two-year longitudinal study of social support following amputation. Disabil Rehabil 26 (2004): 862-874.
48. Madsen UR, Bååth C, Berthelsen CB, et al. A prospective study of short-term functional outcome after dysvascular major lower limb amputation. Int J Orthop Trauma Nurs 28 (2018): 22-29.
49. Shah S, Vanclay F, Cooper B. Improving the sensitivity of the Barthel Index for stroke rehabilitation. J Clin Epidemiol 42 (1989): 703-709.
50. Madsen UR, Bååth C, Berthelsen CB, et al. A prospective study of short-term functional outcome after dysvascular major lower limb amputation. Int J Orthop Trauma Nurs 28 (2018): 22-29.
51. Brunelli S, Fusco A, Iosa M, et al. Functional Outcome After Lower Limb Amputation: Is Hyperhomocysteinemia a Predictive Factor?: An Observational Study. Medicine (Baltimore) 94 (2015): 1-1.
52. Venkataraman K, Fong NP, Chan KM, et al. Rehabilitation Outcomes After Inpatient Rehabilitation for Lower Extremity Amputations in Patients With Diabetes. Arch Phys Med Rehabil 97 (2016): 1473-1480.
53. Meier RH, Melton D. Ideal functional outcomes for amputation levels. Phys Med Rehabil Clin N Am 25 (2014): 199-212.
54. Ülger Ö, Yıldırım Şahan T, Çelik SE. A systematic literature review of physiotherapy and rehabilitation approaches to lower-limb amputation. Physiother Theory Pract 34 (2018): 821-834.
55. Penn-Barwell JG. Outcomes in lower limb amputation following trauma: a systematic review and meta-analysis. Injury 42 (2011): 1474-1479.
56. Kaur Y, Cimino SR, Albarico M, et al. Physical Function Outcomes in Patients with Lower-Limb Amputations Due to Trauma: A Systematic Review. J Prosthet Orthot 33 (2021): 88.
57. Seker A, Kara A, Camur S, et al. Comparison of mortality rates and functional results after transtibial and transfemoral amputations due to diabetes in elderly patients-a retrospective study. Int J Surg 33 (2016): 78-82.
58. Feipel V, Parent C, Dugailly PM, et al. Development of kinematics tests for the evaluation of lumbar proprioception and equilibration. Clin Biomech 18 (2003): 612-618.
59. Gailey RS, Wenger MA, Raya M, et al. Energy expenditure of trans-tibial amputees during ambulation at self-selected pace. Prosthet Orthot Int 18 (1994): 84-91.
60. Miramand L, Moisan G, Richard V, et al. Whole body movement strategies during sit-to-stand and stair ascent in individuals with a lower limb amputation: A systematic review. Clin Biomech 100 (2022): 105811.
61. Chopra A, Azarbal AF, Jung E, et al. Ambulation and functional outcome after major lower extremity amputation. J Vasc Surg 67 (2018): 1521-1529.
62. Stineman MG, Kwong PL, Kurichi JE, et al. The effectiveness of inpatient rehabilitation in the acute postoperative phase of care after transtibial or transfemoral amputation: study of an integrated health care delivery system. Arch Phys Med Rehabil 89 (2008): 1863-1872.
63. Alhossary A, Ang WT, Chua KSG, et al. Identification of Secondary Biomechanical Abnormalities in the Lower Limb Joints after Chronic Transtibial Amputation: A Proof-of-Concept Study Using SPM1D Analysis. Bioengineering 9 (2022): 293.
64. Darter BJ, Hawley CE, Armstrong AJ, et al. Factors Influencing Functional Outcomes and Return-to-Work After Amputation: A review of the literature. J Occup Rehabil 28 (2018): 656-665.
65. Association Between Mental Health Burden, Clinical Presentation, and Outcomes in Individuals With Symptomatic Peripheral Artery Disease: A Scientific Statement From the American Heart Association. Circulation.
66. Darter BJ, Hawley CE, Armstrong AJ, et al. Factors Influencing Functional Outcomes and Return-to-Work After Amputation: A Review of the Literature. J Occup Rehabil 28 (2018): 656-665.
67. Clemens SM, Kershaw KN, McDonald CL, et al. Disparities in functional recovery after dysvascular lower limb amputation are associated with employment status and self-efficacy. Disabil Rehabil 45 (2023): 2280-2287.
68. Sions JM, Seth M, Pohlig RT, et al. Key Modifiable Factors in Community Participation Among Adults With Lower Limb Amputation. Am J Phys Med Rehabil 102 (2023): 803-809.
69. Erbes CR, Ferguson J, Yang K, et al. Amputation-specific and generic correlates of participation among Veterans with lower limb amputation. PloS One 17 (2022): e0270753.
70. Webster JB, Crunkhorn A, Sall J, et al. Clinical Practice Guidelines for the Rehabilitation of Lower Limb Amputation: An Update from the Department of Veterans Affairs and Department of Defense. Am J Phys Med Rehabil 98 (2019): 820-829.
71. Webster JB, Crunkhorn A, Sall J, et al. Clinical Practice Guidelines for the Rehabilitation of Lower Limb Amputation: An Update from the Department of Veterans Affairs and Department of Defense. Am J Phys Med Rehabil 98 (2019): 820-829.
72. Webster JB, Poorman CE, Cifu DX. Guest editorial: Department of Veterans Affairs Amputations System of care: 5 years of accomplishments and outcomes. J Rehabil Res Dev 51 (2014): vii-xvi.
73. Roșca AC, Baciu CC, Burtăverde V, et al. Psychological Consequences in Patients With Amputation of a Limb. An Interpretative-Phenomenological Analysis. Front Psychol 12 (2021).
74. Miller MJ, Cook PF, Magnusson DM, et al. Self-Efficacy and Social Support are Associated with Disability for Ambulatory Prosthesis Users After Lower-Limb Amputation. PM R 13 (2021): 453-460.
75. Calabrese L, Maffoni M, Torlaschi V, et al. What Is Hidden behind Amputation? Quanti-Qualitative Systematic Review on Psychological Adjustment and Quality of Life in Lower Limb Amputees for Non-Traumatic Reasons. Healthcare 11 (2023): 1661.
76. Mathis SL. Factors associated with mobility apprehension in persons with lower limb amputation. Prosthet Orthot Int 44 (2020): 208.
77. Trimble JR, Jessamine JM, Bettin K, et al. Peer-mentorship among people with lower limb amputations living in small communities. Aust Occup Ther J 72 (2025): e70031.
78. Bourque MO, Schneider KL, Calamari JE, et al. Combining physical therapy and cognitive behavioral therapy techniques to improve balance confidence and community participation in people with unilateral transtibial amputation who use lower limb prostheses: a study protocol for a randomized sham-control clinical trial. Trials 20 (2019): 812.
79. Which Interventions Enhance Pain Self-efficacy in People With Chronic Musculoskeletal Pain? A Systematic Review With Meta-analysis of Randomized Controlled Trials, Including Over 12 000 Participants. Journal of Orthopaedic & Sports Physical Therapy.
80. Alperstein D, Sharpe L. The Efficacy of Motivational Interviewing in Adults With Chronic Pain: A Meta-Analysis and Systematic Review. J Pain 17 (2016): 393-403.
81. Eldaly AS, Avila FR, Torres-Guzman RA, et al. Virtual and Augmented Reality in Management of Phantom Limb Pain: A Systematic Review (2024).
82. Cheung JCW, Cheung DSK, Ni M, et al. X-reality for phantom limb management for amputees: A systematic review and meta-analysis. Eng Regen 4 (2023): 134-151.
83. Perry BN, Armiger RS, Wolde M, et al. Clinical Trial of the Virtual Integration Environment to Treat Phantom Limb Pain With Upper Extremity Amputation. Front Neurol 9 (2018).
84. Dumanian GA, Potter BK, Mioton LM, et al. Targeted Muscle Reinnervation Treats Neuroma and Phantom Pain in Major Limb Amputees: A Randomized Clinical Trial. Ann Surg 270 (2019): 238.
85. Bishay J, Yeap I, Wang T. The effectiveness of targeted muscle reinnervation in reducing pain and improving quality of life for patients following lower limb amputation. J Plast Reconstr Aesthet Surg 92 (2024): 288-298.
86. Wu J, Zhang Y, Zhang X, et al. Regenerative Peripheral Nerve Interfaces Effectively Prevent Neuroma Formation After Sciatic Nerve Transection in Rats. Front Mol Neurosci 15 (2022).
87. Woo SL, Kung TA, Brown DL, et al. Regenerative Peripheral Nerve Interfaces for the Treatment of Postamputation Neuroma Pain: A Pilot Study. Plast Reconstr Surg Glob Open 4 (2016): e1038.
88. Berberoglu I, Burke KL, Cederna PS, et al. Regenerative peripheral nerve interfaces (RPNIs): an overview of innovative surgical approaches. Plast Aesthetic Res 11 (2024): N/A-N/A.
89. Fabre I, Thompson D, Gwilym B, et al. Surgical Techniques of, and Outcomes after, Distal Muscle Stabilization in Transfemoral Amputation: A Systematic Review and Narrative Synthesis. Ann Vasc Surg 98 (2024): 182-193.
90. General Principles of Amputation Surgery. UW Orthopaedic Surgery and Sports Medicine.
91. Handford C, McMenemy L, Kendrew J, et al. Improving outcomes for amputees: The health-related quality of life and cost utility analysis of osseointegration prosthetics in transfemoral amputees. Injury 53 (2022): 4114-4122.
92. Nguyen TT, Wang B, Alas H, et al. Prosthesis Embodiment in Lower Extremity Limb Loss: A Narrative Review. Appl Sci 15 (2025): 4952.
93. Zaid MB, OʼDonnell RJ, Potter BK, et al. Orthopaedic Osseointegration: State of the Art. J Am Acad Orthop Surg 27 (2019): e977-e985.
94. Pasquina CPF, Carvalho AJ, Sheehan TP. Ethics in Rehabilitation: Access to Prosthetics and Quality Care Following Amputation. AMA J Ethics 17 (2015): 535-546.
95. Davie-Smith F, Paul L, Stuart W, et al. The Influence of Socio-economic Deprivation on Mobility, Participation, and Quality of Life Following Major Lower Extremity Amputation in the West of Scotland. Eur J Vasc Endovasc Surg 57 (2019): 554-560.
96. Sayeed MSI, Oakman J, Stuckey R. Factors influencing access to and participation in rehabilitation for people with lower limb amputation in East, South, and Southeast Asian developing countries: the perspective of rehabilitation professionals – a qualitative study. Disability and Rehabilitation 46 (2023): 2097-2116.
97. Association of Race, Ethnicity, and Gender to Disparities in Functional Recovery and Social Health After Major Lower Limb Amputation: A Cross-sectional Pilot Study.
98. Ennion L, Johannesson A. A qualitative study of the challenges of providing pre-prosthetic rehabilitation in rural South Africa. Prosthet Orthot Int 42 (2018): 179-186.
99. Ennion L, Manig S. Experiences of lower limb prosthetic users in a rural setting in the Mpumalanga Province, South Africa. Prosthet Orthot Int 43 (2019): 170-179.
100. Hammond B, Abu KA, Anyittey-Kokor D, et al. Determinants of utilization of prostheses and orthoses following lower limb amputation in Sub-Saharan Africa: A systematic review. J Orthop Rep 4 (2025): 100528.
101. Kannenberg A. Active Upper-Limb Prostheses: The International Perspective. JPO J Prosthet Orthot 29 (2017): P57.
102. Kannenberg A, Seidinger S. Health Economics in the Field of Prosthetics and Orthotics: A Global Perspective. Can Prosthet Orthot J 4 (2021): 35298.
103. Miller MJ, Cook PF, Magnusson DM, et al. Self-Efficacy and Social Support are Associated with Disability for Ambulatory Prosthesis Users After Lower-Limb Amputation. PM R 13 (2021): 453-460.
104. Erbes CR, Ferguson J, Yang K, et al. Amputation-specific and generic correlates of participation among Veterans with lower limb amputation. PLOS ONE 17 (2022): e0270753.
105. Aljuhani WS, Alhussaini AA, Alangari HS, et al. Community perception and acceptance of patients with prosthetic devices after disabilities in Saudi Arabia. J Musculoskelet Surg Res 7 (2023): 29-33.
106. AlMehman DA, Faden AS, Aldahlawi BM, et al. Post-amputation pain among lower limb amputees in a tertiary care hospital in Jeddah, Saudi Arabia. Saudi Med J 43 (2022): 187-196.
107. Immediate and long term phantom limb pain in patients with amputations. PAIN.
108. Davis RW. Phantom sensation, phantom pain, and stump pain. Arch Phys Med Rehabil 74 (1993): 79-91.
109. Allami M, Faraji E, Mohammadzadeh F, et al. Chronic musculoskeletal pain, phantom sensation, phantom and stump pain in veterans with unilateral below-knee amputation. Scand J Pain 19 (2019): 779-787.
110. List EB, Krijgh DD, Martin E, et al. Prevalence of residual limb pain and symptomatic neuromas after lower extremity amputation: a systematic review and meta-analysis. Pain 162 (2021): 1906-1913.
111. Draper-Rodi J, Delion T, MacMillan A, et al. Primary and secondary prevention of musculoskeletal pain and disability in chiropractic, osteopathy, and physiotherapy: A scoping review. Int J Osteopath Med 53 (2024): 100725.
112. Huang DX, Yang MX, Jiang ZM, et al. Nerve trunk healing and neuroma formation after nerve transection injury. Front Neurol 14 (2023).
113. Halbert J, Crotty M, Cameron ID. Evidence for the optimal management of acute and chronic phantom pain: a systematic review. Clin J Pain 18 (2002): 84-92.
114. Aydın T, Şen Eİ, Kesiktas N, et al. The Effect of Postamputation Pain and Phantom Sensations on Prosthesis Use, Body Image, and Quality of Life in Patients with Lower-extremity Amputation. Agri 33 (2021): 183-189.
115. Brauckmann V, Mönninghoff S, Block OM, et al. Report on Prosthetic Fitting, Mobility, and Overall Satisfaction after Major Limb Amputation at a German Maximum Care Provider. Appl Sci 14 (2024): 7274.
116. Erlenwein J, Diers M, Ernst J, et al. Clinical updates on phantom limb pain. PAIN Rep 6 (2021): e888.
117. Pain After Lower Limb Amputations: Insights from the Heidelberg Amputation Registry. Medicina 60 (2024): 1887.
118. Wurdeman SR, Stevens PM, Campbell JH. Mobility Analysis of AmpuTees (MAAT I): Quality of life and satisfaction are strongly related to mobility for patients with a lower limb prosthesis. Prosthet Orthot Int 42 (2018): 498-503.
119. Knight AD, Dearth CL, Hendershot BD. Deleterious Musculoskeletal Conditions Secondary to Lower Limb Loss: Considerations for Prosthesis-Related Factors. Adv Wound Care 10 (2021): 671-684.
120. Butowicz CM, Dearth CL, Hendershot BD. Joint power distribution does not change within the contralateral limb one year after unilateral limb loss. Gait Posture 73 (2019): 8-13.
121. Örücü Atar M, Demir Y, Tekin E, et al. Kinesiophobia and associated factors in patients with traumatic lower extremity amputation. Turk J Phys Med Rehabil 68 (2022): 493-500.
122. Hooten WM. Chronic Pain and Mental Health Disorders: Shared Neural Mechanisms, Epidemiology, and Treatment. Mayo Clin Proc 91 (2016): 955-970.
123. Zale EL, Ditre JW. Pain-Related Fear, Disability, and the Fear-Avoidance Model of Chronic Pain. Curr Opin Psychol 5 (2015): 24-30.
124. Psychological Interventions in Patients with Physical Pain: A Focus on Catastrophizing and Resilience—A Systematic Review. Healthcare 13 (2025): 581.
125. The associations of chronic pain and 24-h movement behaviors with incident mental disorders: evidence from a large-scale cohort study. BMC Med.
126. Marshall PWM, Schabrun S, Knox MF. Physical activity and the mediating effect of fear, depression, anxiety, and catastrophizing on pain related disability in people with chronic low back pain. PLOS ONE 12 (2017): e0180788.
127. Hsu E, Cohen SP. Postamputation pain: epidemiology, mechanisms, and treatment. J Pain Res 6 (2013): 121-136.
128. Alviar MJM, Hale T, Lim-Dungca M. Pharmacologic interventions for treating phantom limb pain. Cochrane Database Syst Rev 2016 (2016): CD006380.
129. Doshi TL, Dolomisiewicz E, Caterina MJ, et al. Postamputation pain: a multidisciplinary review of epidemiology, mechanisms, prevention, and treatment. Reg Anesth Pain Med 50 (2025): 175-183.
130. Privitera R, Birch R, Sinisi M, et al. Capsaicin 8% patch treatment for amputation stump and phantom limb pain: a clinical and functional MRI study. J Pain Res 10 (2017): 1623-1634.
131. Le ELH, Greyson MA, Constantine RS, et al. A review of pain outcomes following targeted muscle reinnervation in lower extremity limb pain. Plast Aesthetic Res 9 (2022): N/A-N/A.
132. Walsh AR, Lu J, Rodriguez E, et al. The Current State of Targeted Muscle Reinnervation: A Systematic Review. J Reconstr Microsurg 39 (2023): 238-244.
133. Raut R, Shams S, Rasheed M, et al. Spinal Cord Stimulation in The Treatment of Phantom Limb Pain: A Case Report and Review of Literature. Neurol India 69 (2021): 157.
134. Srinivasan N, Zhou B, Park E. Dorsal Root Ganglion Stimulation for the Management of Phantom Limb Pain: A Scoping Review. Pain Physician 25 (2022): E1174-E1182.
135. Harrison C, Epton S, Bojanic S, et al. The Efficacy and Safety of Dorsal Root Ganglion Stimulation as a Treatment for Neuropathic Pain: A Literature Review. Neuromodulation 21 (2018): 225-233.
136. Guémann M, Olié E, Raquin L, et al. Effect of mirror therapy in the treatment of phantom limb pain in amputees: A systematic review of randomized placebo-controlled trials does not find any evidence of efficacy. Eur J Pain 27 (2023): 3-13.
137. Foell J, Bekrater-Bodmann R, Diers M, et al. Mirror therapy for phantom limb pain: Brain changes and the role of body representation. Eur J Pain 18 (2014): 729-39.
138. Hilton L, Hempel S, Ewing BA, et al. Mindfulness Meditation for Chronic Pain: Systematic Review and Meta-analysis. Ann Behav Med 51 (2017): 199-213.
139. Skelly AC, Chou R, Dettori JR, et al. Introduction. In: Integrated and Comprehensive Pain Management Programs: Effectiveness and Harms. Agency for Healthcare Research and Quality (US) (2021).
140. Kovačević I, Pavić J, Filipović B, et al. Integrated Approach to Chronic Pain—The Role of Psychosocial Factors and Multidisciplinary Treatment: A Narrative Review. Int J Environ Res Public Health 21 (2024): 1135.
141. Fuenzalida Squella SA, Kannenberg A, Brandão Benetti Â. Enhancement of a prosthetic knee with a microprocessor-controlled gait phase switch reduces falls and improves balance confidence and gait speed in community ambulators with unilateral transfemoral amputation. Prosthet Orthot Int 42 (2018): 228-235.
142. McGrath M, Laszczak P, Zahedi S, et al. The influence of a microprocessor-controlled hydraulic ankle on the kinetic symmetry of trans-tibial amputees during ramp walking: A case series. J Rehabil Assist Technol Eng 5 (2018): 2055668318790650.
143. Hunt GR, Hood S, Gabert L, et al. Can a powered knee-ankle prosthesis improve weight-bearing symmetry during stand-to-sit transitions in individuals with above-knee amputations? J NeuroEngineering Rehabil 20 (2023): 58.
144. Overmann AL, Forsberg JA. The state of the art of osseointegration for limb prosthesis. Biomed Eng Lett 10 (2020): 5-16.
145. Hoellwarth JS, Tetsworth K, Oomatia A, et al. Association Between Osseointegration of Lower Extremity Amputation and Mortality Among Adults. JAMA Netw Open.
146. Reetz D, Atallah R, Mohamed J, et al. Safety and Performance of Bone-Anchored Prostheses in Persons with a Transfemoral Amputation: A 5-Year Follow-up Study. J Bone Joint Surg Am 102 (2020): 1329-1335.
147. Hillock R, Daniel A, Benjamin. Patient Outcomes in a Novel Osseointegrated Device for Transfemoral Amputation: A Case Series. Journal of Orthopaedic Experience & Innovation 5 (2024).
148. Simon AM, Turner KL, Miller LA, et al. Myoelectric prosthesis hand grasp control following targeted muscle reinnervation in individuals with transradial amputation. PLOS ONE 18 (2023): e0280210.
149. Gupta S, Loh KJ, Pedtke A. Sensing and actuation technologies for smart socket prostheses. Biomed Eng Lett 10 (2019): 103-118.
150. Lee C, Vaskov AK, Gonzalez MA, et al. Use of regenerative peripheral nerve interfaces and intramuscular electrodes to improve prosthetic grasp selection: a case study. J Neural Eng 19 (2022).
151. Ilfeld BM, Khatibi B, Maheshwari K, et al. Patient-centered results from a multicenter study of continuous peripheral nerve blocks and postamputation phantom and residual limb pain: secondary outcomes from a randomized, clinical trial. Reg Anesth Pain Med 48 (2023): 471.
152. Nanivadekar AC, Chandrasekaran S, Helm ER, et al. Closed-loop stimulation of lateral cervical spinal cord in upper-limb amputees to enable sensory discrimination: a case study. Sci Rep 12 (2022): 17002.
153. Cohen SP, Gilmore CA, Rauck RL, et al. Percutaneous Peripheral Nerve Stimulation for the Treatment of Chronic Pain Following Amputation. Mil Med 184 (2019): e267-e274.
154. Albright-Trainer B, Phan T, Trainer RJ, et al. Peripheral nerve stimulation for the management of acute and subacute post-amputation pain: a randomized, controlled feasibility trial. Pain Manag 12 (2022): 357-369.
155. Kikkert S, Johansen-Berg H, Tracey I, et al. Reaffirming the link between chronic phantom limb pain and maintained missing hand representation. Cortex 106 (2018): 174-184.
156. Eldabe S, Burger K, Moser H, et al. Dorsal Root Ganglion (DRG) Stimulation in the Treatment of Phantom Limb Pain (PLP). Neuromodulation 18 (2015): 610-616.
157. Jaffee S, Verma R, Vaezi M, et al. A scoping review of spinal cord stimulation for phantom limb pain. Interv Pain Med 4 (2025): 100571.
158. Malavera A, Silva FA, Fregni F, et al. Repetitive Transcranial Magnetic Stimulation for Phantom Limb Pain in Land Mine Victims: A Double-Blinded, Randomized, Sham-Controlled Trial. J Pain 17 (2016): 911-918.
159. Bolognini N, Spandri V, Ferraro F, et al. Immediate and Sustained Effects of 5-Day Transcranial Direct Current Stimulation of the Motor Cortex in Phantom Limb Pain. J Pain 16 (2015): 657-665.
160. Pacheco-Barrios K, Meng X, Fregni F. Neuromodulation Techniques in Phantom Limb Pain: A Systematic Review and Meta-analysis. Pain Med 21 (2020): 2310-2322.
161. Frost CM, Ursu DC, Flattery SM, et al. Regenerative peripheral nerve interfaces for real-time, proportional control of a Neuroprosthetic hand. J Neuroengineering Rehabil 15 (2018): 108.
162. Pinto CB, Saleh Velez FG, Bolognini N, et al. Optimizing Rehabilitation for Phantom Limb Pain Using Mirror Therapy and Transcranial Direct Current Stimulation: A Randomized, Double-Blind Clinical Trial Study Protocol. JMIR Res Protoc 5 (2016): e138.
163. Meyer P, Matthes C, Kusche KE, et al. Imaginative resonance training (IRT) achieves elimination of amputees’ phantom pain (PLP) coupled with a spontaneous in-depth proprioception of a restored limb as a marker for permanence and supported by pre-post functional magnetic resonance imaging (fMRI). Psychiatry Res 202 (2012): 175-179.
164. Chandler CC, Serbin RP, Frix JT, et al. An introduction to virtual reality-based Targeted Brain Rehabilitation to treat phantom limb pain in the upper extremity amputee population. J Hand Ther (2026).
165. Hagiga A, Aly M, Gumaa M, et al. Targeted muscle reinnervation in managing post-amputation related pain: A systematic review and meta-analysis. Pain Pract 23 (2023): 922-932.
166. ElAbd R, Dow T, Jabori S, et al. Pain and Functional Outcomes following Targeted Muscle Reinnervation: A Systematic Review. Plast Reconstr Surg 153 (2024): 494-508.
167. Corbett M, South E, Harden M, et al. Brain and spinal stimulation therapies for phantom limb pain: a systematic review. Health Technol Assess 22 (2018): 1-94.
168. Pacheco-Barrios K, Martinez-Magallanes D, Naqui CX, et al. Using Home-based, Remotely Supervised, Transcranial Direct Current Stimulation for Phantom Limb Pain. J Vis Exp 205 (2024).
169. Pettersen E, Sassu P, Pedrini FA, et al. Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain. J Vis Exp 205 (2024).
170. Langeveld M, Raasveld FV, Hundepool CA, et al. Neuropathic Pain after Major Limb Amputation: A Cross-Sectional Study. Plast Reconstr Surg 155 (2025): 419e-427e.
171. Lans J, Groot OQ, Hazewinkel MHJ, et al. Factors Related to Neuropathic Pain Following Lower Extremity Amputation. Plast Reconstr Surg 150 (2022): 446-455.
172. Chappell AG, Ramsey MD, Park S, et al. Targeted Muscle Reinnervation—an Up-to-Date Review: Evidence, Indications, and Technique. Arch Plast Surg 52 (2025): 153-168.
173. Lee JC, Kubiak CA, Best CSW, et al. Regenerative Peripheral Nerve Interface Surgery to Treat Chronic Postamputation Pain: A Prospective Study in Major Lower Limb Amputation Patients. Ann Surg Open 6 (2025): e535.
174. Best CS, Cederna PS, Kung TA. Regenerative Peripheral Nerve Interface (RPNI) Surgery for Mitigation of Neuroma and Postamputation Pain. JBJS Essent Surg Tech 14 (2024): e23.00009.
175. Bowen JB, Wee CE, Kalik J, et al. Targeted Muscle Reinnervation to Improve Pain, Prosthetic Tolerance, and Bioprosthetic Outcomes in the Amputee. Adv Wound Care 6 (2017): 261-267.
176. de Luca AC, Lacour SP, Raffoul W, et al. Extracellular matrix components in peripheral nerve repair: how to affect neural cellular response and nerve regeneration? Neural Regen Res 9 (2014): 1943-1948.
177. Xu Y, Liu X, Ahmad MA, et al. Engineering cell-derived extracellular matrix for peripheral nerve regeneration. Mater Today Bio 27 (2024): 101125.
178. Yu L, Bennett CJ, Lin CH, et al. Scaffold design considerations for peripheral nerve regeneration. J Neural Eng 21 (2024): 10.1088/1741-2552/ad628d.
179. Thomson SE, Ng NY, Riehle MO, et al. Bioengineered nerve conduits and wraps for peripheral nerve repair of the upper limb. Cochrane Database Syst Rev 2022 (2022): CD012574.
180. Lam TC, Wu Z, Lee SJ, et al. Peripheral Nerve Regeneration Reimagined: Cutting-Edge Biomaterials and Biotechnological Innovations. Bioengineering 12 (2025): 864.
181. Kuffler DP, Reyes O, Sosa IJ, et al. Clinically Reducing/Eliminating Chronic Neuropathic Pain by Bridging Peripheral Nerve Gaps with an Autograft within a PRP-Filled Collagen Tube. J Pain Res 18 (2025): 3207-3216.
182. Kuffler DP. Evolving techniques for reducing phantom limb pain. Exp Biol Med 248 (2023): 561-572.
183. Isackson D, McGill LD, Bachus KN. Percutaneous Implants with Porous Titanium Dermal Barriers: An In Vivo Evaluation of Infection Risk. Med Eng Phys 33 (2011): 418-426.
184. Stein S, Kruck L, Warnecke D, et al. Osseointegration of titanium implants with a novel silver coating under dynamic loading. Eur Cell Mater 39 (2020): 249-259.
185. Savvidou OD, Kaspiris A, Trikoupis I, et al. Efficacy of antimicrobial coated orthopaedic implants on the prevention of periprosthetic infections: a systematic review and meta-analysis. J Bone Jt Infect 5 (2020): 212-222.
186. Bohara S, Suthakorn J. Surface coating of orthopedic implant to enhance the osseointegration and reduction of bacterial colonization: a review. Biomater Res 26 (2022): 26.
187. Tillander J, Hagberg K, Berlin Ö, et al. Osteomyelitis Risk in Patients With Transfemoral Amputations Treated With Osseointegration Prostheses. Clin Orthop 475 (2017): 3100-3108.
188. Fearing BV, Gitajn IL, Romereim SM, et al. Basic science review of transcutaneous osseointegration: current status, research gaps and needs, and defining future directions. OTA Int 8 (2025): e367.
189. Tirrell AR, Kim KG, Rashid W, et al. Patient-reported Outcome Measures following Traumatic Lower Extremity Amputation: A Systematic Review and Meta-analysis. Plast Reconstr Surg Glob Open 9 (2021): e3920.
190. Ghai S, Hitzig SL, Eberlin L, et al. Reporting of Rehabilitation Outcomes in the Traumatic Lower Limb Amputation Literature: A Systematic Review. Arch Phys Med Rehabil 105 (2024): 1158-1170.
191. Clarke L, Ridgewell E, Dillon MP. Development of a Core Outcome Set for users and funders of lower-limb prosthetic interventions (PI-COS): a step to inform the benefits measured in prosthetic health economic evaluations. Disabil Rehabil 46 (2024): 4407-4419.
192. Ambler GK, Brookes-Howell L, Jones JAR, et al. Development of Core Outcome Sets for People Undergoing Major Lower Limb Amputation for Complications of Peripheral Vascular Disease. Eur J Vasc Endovasc Surg 60 (2020): 730-738.
193. Hopewell S, Chan AW, Collins GS, et al. CONSORT 2025 Statement: Updated Guideline for Reporting Randomized Trials. JAMA 333 (2025): 1998-2005.
194. Hao J, Chen Z, Remis A, et al. Virtual Reality-Based Rehabilitation to Restore Motor Function in People With Amputation: A Systematic Literature Review. Am J Phys Med Rehabil 102 (2023): 468-474.
195. Sheehan RC, Rábago CA, Rylander JH, et al. Use of Perturbation-Based Gait Training in a Virtual Environment to Address Mediolateral Instability in an Individual With Unilateral Transfemoral Amputation. Phys Ther 96 (2016): 1896-1904.
196. Darter BJ, Wilken JM. Gait training with virtual reality-based real-time feedback: improving gait performance following transfemoral amputation. Phys Ther 91 (2011): 1385-1394.
197. Tong X, Wang X, Cai Y, et al. “I Dreamed of My Hands and Arms Moving Again”: A Case Series Investigating the Effect of Immersive Virtual Reality on Phantom Limb Pain Alleviation. Front Neurol 11 (2020): 876.
198. Matamala-Gomez M, Donegan T, Bottiroli S, et al. Immersive Virtual Reality and Virtual Embodiment for Pain Relief. Front Hum Neurosci 13 (2019): 279.
199. Chau B, Phelan I, Ta P, et al. Immersive Virtual Reality Therapy with Myoelectric Control for Treatment-resistant Phantom Limb Pain: Case Report. Innov Clin Neurosci 14 (2017): 3-7.
200. Kurtaran M, Çelik D. Effectiveness of telerehabilitation-based structured exercise program in individuals with unilateral transtibial amputation: a randomized controlled study. Disabil Rehabil 46 (2024): 5651-5659.
201. Hunt CL, Sun Y, Wang S, et al. Limb loading enhances skill transfer between augmented and physical reality tasks during limb loss rehabilitation. J NeuroEngineering Rehabil 20 (2023): 16.
202. Ettefagh A, Roshan Fekr A. Technological advances in lower-limb tele-rehabilitation: A review of literature. J Rehabil Assist Technol Eng 11 (2024): 20556683241259256.
203. Garske CA, Dyson M, Dupan S, et al. Serious Games Are Not Serious Enough for Myoelectric Prosthetics. JMIR Serious Games 9 (2021): e28079.
204. Carro RM, Costales FG, Ortigosa A. Serious Games for Training Myoelectric Prostheses through Multi-Contact Devices. Children 9 (2022): 423.
205. Winslow BD, Ruble M, Huber Z. Mobile, Game-Based Training for Myoelectric Prosthesis Control. Front Bioeng Biotechnol 6 (2018): 94.
206. Ambron E, Miller A, Kuchenbecker KJ, et al. Immersive Low-Cost Virtual Reality Treatment for Phantom Limb Pain: Evidence from Two Cases. Front Neurol 9 (2018): 67.
207. Abbas RL, Cooreman D, Al Sultan H, et al. The Effect of Adding Virtual Reality Training on Traditional Exercise Program on Balance and Gait in Unilateral, Traumatic Lower Limb Amputee. Games Health J 10 (2021): 50-56.
208. Naqvi WM, Naqvi IW, Mishra GV, et al. The future of telerehabilitation: embracing virtual reality and augmented reality innovations. Pan Afr Med J 47 (2024): 157.
209. Simón-Vicente L, Rodríguez-Cano S, Delgado-Benito V, et al. Cybersickness. A systematic literature review of adverse effects related to virtual reality. Neurologia 39 (2024): 701-709.
210. Kaufman KR, Bernhardt KA, Symms K. Functional assessment and satisfaction of transfemoral amputees with low mobility (FASTK2): A clinical trial of microprocessor-controlled vs. non-microprocessor-controlled knees. Clin Biomech 58 (2018): 116-122.
211. Bright T, Wallace S, Kuper H. A Systematic Review of Access to Rehabilitation for People with Disabilities in Low- and Middle-Income Countries. Int J Environ Res Public Health 15 (2018): 2165.
212. Kurichi JE, Xie D, Kwong PL, et al. Factors Associated With Late Specialized Rehabilitation among Veterans with Lower Extremity Amputation Who Underwent Immediate Postoperative Rehabilitation. Am J Phys Med Rehabil 90 (2011): 387-398.
213. Naidoo U, Ennion L. Barriers and facilitators to utilisation of rehabilitation services amongst persons with lower-limb amputations in a rural community in South Africa. Prosthet Orthot Int 43 (2019): 95-103.
214. Girijala RL, Bush RL. Review of Socioeconomic Disparities in Lower Extremity Amputations: A Continuing Healthcare Problem in the United States. Cureus 10 (2018): e3418.
215. Chen C, Hanson M, Chaturvedi R, et al. Economic benefits of microprocessor controlled prosthetic knees: a modeling study. J NeuroEngineering Rehabil 15 (2018): 62.
216. Webster J, Young P, Kiecker J. Telerehabilitation for Amputee Care. Phys Med Rehabil Clin 32 (2021): 253-262.
217. Jenson AN, Branch B, Richard JM, et al. Phantom Limb Pain Assessment Tools: A Literature Review Exploring Strengths and Limitations. Arch Rehabil Res Clin Transl 7 (2025): 100453.
218. Miller R, Ambler GK, Ramirez J, et al. Patient Reported Outcome Measures for Major Lower Limb Amputation Caused by Peripheral Artery Disease or Diabetes: A Systematic Review. Eur J Vasc Endovasc Surg 61 (2021): 491-501.
219. Lathouwers E, Díaz MA, Maricot A, et al. Therapeutic benefits of lower limb prostheses: a systematic review. J NeuroEngineering Rehabil 20 (2023): 4.
220. Kaufman KR, Bernhardt K, Murphy S, et al. Creation of a Limb Loss and Preservation Registry for Improving the Quality of Patient Care in the United States. Arch Rehabil Res Clin Transl 6 (2024): 100356.
221. Tan JM, Halford GRJ, Lukin M, et al. Recommendations from the ISPO lower-limb COMPASS: Patient-reported and performance-based outcome measures. Prosthet Orthot Int 47 (2023): 13-25.
222. Kamrad I, Söderberg B, Örneholm H, et al. SwedeAmp-the Swedish Amputation and Prosthetics Registry: 8-year data on 5762 patients with lower limb amputation show sex differences in amputation level and in patient-reported outcome. Acta Orthop 91 (2020): 464-470.
223. Ennion L, Rhoda A. Roles and challenges of the multidisciplinary team involved in prosthetic rehabilitation, in a rural district in South Africa. J Multidiscip Healthc 9 (2016): 565-573.
224. Ladlow P, Nightingale TE, McGuigan MP, et al. Predicting ambulatory energy expenditure in lower limb amputees using multi-sensor methods. PLoS ONE 14 (2019): e0209249.
225. Bastas G, Fleck JJ, Peters RA, et al. IMU-Based Gait Analysis in Lower Limb Prosthesis Users: Comparison of Step Demarcation Algorithms. Gait Posture 64 (2018): 30-37.
226. Hafner B, Sanders J. Considerations for development of sensing and monitoring tools to facilitate treatment and care of persons with lower limb loss. J Rehabil Res Dev 51 (2014): 1-14.
227. Chadwell A, Diment L, Micó-Amigo M, et al. Technology for monitoring everyday prosthesis use: a systematic review. J NeuroEngineering Rehabil 17 (2020): 93.
228. Hanley MA, Jensen MP, Ehde DM, et al. Psychosocial predictors of long-term adjustment to lower-limb amputation and phantom limb pain. Disabil Rehabil 26 (2004): 882-893.
229. Knezevic A, Arsenovic J, Garipi E, et al. Machine Learning Model for Predicting Walking Ability in Lower Limb Amputees. J Clin Med 13 (2024): 6763.
230. Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 1 - A scoping review of healing and non-healing definitions. Can Prosthet Orthot J 7 (2024): 43715.
231. Campat C, O’Banion LA. Multidisciplinary protocols are an important part of enhanced recovery after major lower extremity amputation. Front Surg 12 (2025): 1637121.
232. Jo SH, Kang SH, Seo WS, et al. Psychiatric understanding and treatment of patients with amputations. Yeungnam Univ J Med 38 (2021): 194-201.
233. Tian Y, Valle G, Cederna PS, et al. The Next Frontier in Neuroprosthetics: Integration of Biomimetic Somatosensory Feedback. Biomimetics 10 (2025): 130.
234. Cady SR, Lambrecht JM, Dsouza KT, et al. First-in-human implementation of a bidirectional somatosensory neuroprosthetic system with wireless communication. J NeuroEngineering Rehabil 22 (2025): 90.
235. Valle G, Mazzoni A, Iberite F, et al. Biomimetic Intraneural Sensory Feedback Enhances Sensation Naturalness, Tactile Sensitivity, and Manual Dexterity in a Bidirectional Prosthesis. Neuron 100 (2018): 37-45.e7.
236. Clemente F, Valle G, Controzzi M, et al. Intraneural sensory feedback restores grip force control and motor coordination while using a prosthetic hand. J Neural Eng 16 (2019): 026034.
237. Page DM, George JA, Kluger DT, et al. Motor Control and Sensory Feedback Enhance Prosthesis Embodiment and Reduce Phantom Pain After Long-Term Hand Amputation. Front Hum Neurosci 12 (2018): 352.
238. Horgan O, MacLachlan M. Psychosocial adjustment to lower-limb amputation: a review. Disabil Rehabil 26 (2004): 837-850.
239. Phutane P, Santre M, Tiwari K, et al. Depression, anxiety, coping, and resilience among amputees: A cross-sectional tertiary care hospital-based study. Ind Psychiatry J 33 (2024): S59-S63.
240. Morgan SJ, Rowe K, Fitting CC, et al. Use of standardized outcome measures for people with lower limb amputation: A survey of prosthetic practitioners in the United States. Arch Phys Med Rehabil 103 (2022): 1786-1797.
241. Kapural L, Syed Shah N, Fang ZP, et al. Multicenter, Double-Blinded, Randomized, Active-Sham Controlled Clinical Study Design to Assess the Safety and Effectiveness of a Novel High Frequency Electric Nerve Block System in the Treatment of Post-Amputation Pain (The QUEST Study). J Pain Res 15 (2022): 1623-1631.