Wound Healing: Cellular Review With Specific Attention to Postamputation Care
Wound healing is crucial for survival, prevention of infection, and restoration of tissue function. The immune system drives this process with 3 main phases: inflammation, proliferation, and remodeling. Keloids and hypertrophic scars reveal disruptions in these phases, underscoring the balance needed for healing. Limb amputation, a life-changing event, demands careful consideration for healing and function. Factors such as amputation level, surgical technique, and prosthetic fitting shape outcomes, while complications such as heterotopic ossification challenge recovery. Treatment advances including statins and stem cell therapy hold promise, with dermatologists poised to contribute substantially to postamputation care.
Practice Points
- Wound healing in adults is a complex dynamic process that usually takes the greater part of 1 year to completely resolve and is marked by the end of scar formation.
- Postamputation residual limbs are subject to mechanical and biophysical stress to which the overlying skin is not accustomed. Skin treatment aims at mitigating these stresses.
- The major dermatologic barriers to successful wound healing following amputation include infection, skin breakdown, formation of chronic wounds and granulation tissue, heterotopic ossification, and hyperhidrosis.
The occurrence of heterotopic ossification (extraskeletal bone formation) is another notable issue in military amputees.27,55-57 Poor prosthetic fit can lead to skin degradation, necessitating further surgery to address mispositioned bone formations. Orthopedic monitoring supplemented by appropriate imaging studies can benefit postamputation patients by detecting and preventing heterotopic ossification in its early stages.
Dermatologic issues, especially among lower limb amputees, are noteworthy, with a substantial percentage experiencing complications related to socket prosthetics, such as heat, sweating, sores, and skin irritation. Up to 41% of patients are seen regularly for a secondary skin disorder following amputation.58 As one might expect, persistent wounds, blisters, ulcers, and abscesses are some of the most typical cutaneous abnormalities affecting residual limbs with prostheses.27,58 More rare skin conditions also are documented in residual limbs, including cutaneous granuloma, verrucous carcinoma, bullous pemphigoid, and angiodermatitis.27,59-61
Treatments offered in the dermatology clinic often are similar to patients who have not had an amputation. For instance, hyperhidrosis can be treated with prescription antiperspirant, topical aluminum chloride, topical glycopyrronium, botulinum toxin, and iontophoresis, which can greatly decrease skin irritation and malodor. Subcutaneous neurotoxins such as botulinum toxin are especially useful for hyperhidrosis following amputation because a single treatment can last 3 to 6 months, whereas topicals must be applied multiple times per day and can be inherently irritating to the skin.27,62 Furthermore, ablative fractional resurfacing lasers also can help stimulate new collagen growth, increase skin mobility on residual limbs, smooth jagged scars, and aid prosthetic fitting.27,63 Perforated prosthetic liners also may be useful to address issues such as excessive sweating, demonstrating improvements in skin health, reduced sweating problems, and potential avoidance of surgical interventions.64
When comorbid skin conditions are at bay, preventive measures for excessive wound healing necessitate early recognition and timely intervention for residual limbs. Preventive techniques encompass the use of silicone gel sheeting, hypoallergenic microporous tape, and intralesional steroid injections.
Psychological Concerns—An overarching issue following amputation is the psychological toll the process imposes on the patient. Psychological concerns, including anxiety and depression, present additional challenges impacting residual limb hygiene and prosthetic maintenance. Chronic wounds are devastating to patients. These patients consistently express feeling ostracized from their community and anxious about unemployment, leaking fluid, or odor from the wound, as well as other social stigmata.62 Depression and anxiety can hinder a patient’s ability to care for their wound and make them more susceptible to the myriad issues that can ensue.
Recent Developments in Wound Healing
Wound healing is ripe for innovation that could assuage ailments that impact patients following amputation. A 2022 study by Abu El Hawa et al65 illustrated advanced progression in wound healing for patients taking statins, even though the statin group had increased age and number of comorbidities compared with patients not taking statins.
Nasseri and Sharifi66 showed the potential of antimicrobial peptides—small proteins with cationic charges and amphipathic structures exhibiting electrostatic interaction with microbial cell membranes—in promoting wound healing, particularly defensins and cathelicidin LL-37.They also discussed innovative delivery systems, such as nanoparticles and electrospun fibrous scaffolds, highlighting their potential as possibly more effective therapeutics than antibiotics, especially in the context of diabetic wound closure.66 Aimed at increased angiogenesis in the proliferative phase, there is evidence that N-acetylcysteine can increase amputation stump perfusion with the goal of better long-term wound healing and more efficient scar formation.67
Stem cell therapy, particularly employing cells from the human amniotic membrane, represents an auspicious avenue for antifibrotic treatment. Amniotic epithelial cells and amniotic mesenchymal cells, with their self-renewal and multilineage differentiation capabilities, exhibit anti-inflammatory and antifibrotic properties.4,5 A study by Dong et al68 aimed to assess the efficacy of cell therapy, particularly differentiated progenitor cell–based graft transplantation or autologous stem cell injection, in treating refractory skin injuries such as nonrevascularizable critical limb ischemic ulcers, venous leg ulcers, and diabetic lower limb ulcers. The findings demonstrated cell therapy effectively reduced the size of ulcers, improved wound closure rates, and decreased major amputation rates compared with standard therapy. Of note, cell therapy had limited impact on alleviating pain in patients with critical limb ischemia-related cutaneous ulcers.68
Final Thoughts
Wound care following amputation is a multidisciplinary endeavor, necessitating collaboration between many health care professionals. Dermatologists play a crucial role in providing routine care as well as addressing wound healing and related skin issues among amputation patients. As the field progresses, dermatologists are well positioned to make notable contributions and ensure enhanced outcomes, resulting in a better quality of life for patients facing the challenges of limb amputation and prosthetic use.
