Mohs Micrographic Surgery, Optimizing Wound Healing

Function

Understanding the physiology of wound healing is essential for optimizing surgical outcomes and promoting tissue regeneration following MMS. Wound healing after cutaneous surgery is a complex and dynamic process involving intricate cellular and molecular events. The physiological cascade of wound healing can be broadly divided into 4 overlapping phases: hemostasis, inflammation, proliferation, and remodeling.

Hemostasis

Immediately after tissue injury, vasoconstriction and platelet aggregation occur to achieve hemostasis and prevent blood loss. The endothelium of damaged blood vessels rapidly releases endothelin and other vasoconstrictive agents, leading to smooth muscle cell contraction. Concomitantly, circulating platelets adhere to exposed collagen fibers and release granules containing adenosine diphosphate (ADP), thromboxane A2, and serotonin, further promoting platelet aggregation and vasoconstriction. Fibrin clot formation leads to the creation of a temporary matrix. It initiates the release of growth factors, including platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β), essential for subsequent healing phases.[1]

Inflammation

The second phase of wound healing is the inflammatory phase, characterized by the influx of immune cells, such as neutrophils and macrophages, that remove debris and pathogens from the wound site. Neutrophils are among the first responders, migrating through the interstitial tissue in response to chemotactic signals, including interleukin-8 (IL-8) and leukotriene B4 (LTB4). These cells phagocytose bacteria and release proteolytic enzymes and reactive oxygen species to neutralize infectious agents. Macrophages, derived from circulating monocytes, play a critical role in debridement by engulfing apoptotic cells and necrotic tissue. These cells also secrete a wide array of cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1), which amplify the inflammatory response and attract additional immune cells to the wound site.[2]

Proliferation

In the subsequent phase, fibroblasts proliferate and migrate into the wound bed, synthesizing extracellular matrix components such as collagen to restore tissue integrity. Fibroblasts are activated by growth factors, including fibroblast growth factor (FGF) and TGF-β, leading to their differentiation into myofibroblasts, which express α-smooth muscle actin (α-SMA) and contribute to wound contraction. Additionally, keratinocytes at the wound edges proliferate and migrate across the wound bed, a process facilitated by matrix metalloproteinases (MMPs) that degrade the provisional matrix.[3]

Angiogenesis, the formation of new blood vessels, also occurs within the proliferation phase, establishing the healing tissue's oxygen and nutrient supply. This process is driven by vascular endothelial growth factor (VEGF) and involves the proliferation and migration of endothelial cells, resulting in the formation of capillary sprouts that invade the wound matrix.[4]

Remodeling

The newly formed tissue undergoes maturation and reorganization during this final phase, leading to scar formation and tissue remodeling. Collagen fibers are realigned along tension lines, and the extracellular matrix undergoes extensive remodeling mediated by MMPs and their tissue inhibitors (TIMPs).[5] Myofibroblasts play a crucial role in wound contraction by exerting contractile forces on the extracellular matrix. The balance between collagen synthesis and degradation is carefully regulated to prevent excessive scar formation. This highly orchestrated process is tightly regulated by many growth factors, cytokines, and signaling pathways to ensure efficient wound closure and restoration of skin function.

Issues of Concern

Various factors can impede the postoperative wound healing process significantly, thereby leading to complications and suboptimal outcomes. These factors may be related to patient characteristics, wound properties, surgical technique, and postoperative care quality, as discussed below.

Patient-Related Factors

Patient-related factors determine wound healing capacity. Advanced age has been identified as a significant limiting factor, as age-related changes in cellular function, such as decreased keratinocyte and fibroblast proliferative capacity and reduced angiogenesis, can compromise efficient wound healing.[6] Additionally, comorbidities such as diabetes, immunosuppression, and peripheral vascular disease can impair wound healing by disrupting blood flow, immune function, and tissue repair mechanisms.

Diabetes, for example, is associated with leukocyte dysfunction, reduced growth factor production, and neuropathy, which concertedly delay healing and increase the risk of infection. Immunosuppressive states, whether due to medications or underlying conditions, impair the inflammatory phase of wound healing, leading to suboptimal pathogen clearance and delayed progression to the proliferative phase.[7]

Peripheral vascular disease compromises tissue perfusion and oxygenation, essential for collagen synthesis and angiogenesis. Smoking is another notable patient-related factor known to contribute to delayed wound healing.[8] Nicotine and other toxic cigarette components have been shown to cause vasoconstriction, which reduces blood flow to the wound area. Poor circulation lowers hemoglobin's oxygen-carrying capacity, decreases tissue oxygenation, inhibits angiogenesis, and disrupts collagen synthesis and cross-linking, all hindering natural healing.[9]

Wound-Related Factors

Wound-related factors also contribute significantly to the duration of tissue repair and the potential for complications. The size and depth of the wound are critical determinants, with larger and deeper wounds requiring more extensive tissue repair and posing a higher risk of delayed healing.[10] Wounds extending into the subcutaneous tissue or beyond necessitate complex cellular and extracellular matrix activities, increasing the healing time. Moreover, excessive tissue manipulation during surgery can disrupt the wound bed, leading to mechanical tissue damage, compromised circulation, and heightened inflammatory responses. These factors collectively impair the natural healing process and contribute to a prolonged recovery.[11]

Additionally, infections represent a significant impediment to wound healing, as they can cause inflammation and tissue necrosis and impair cellular proliferation, further delaying the healing process. Infections prolong inflammatory responses, leading to excessive production of MMPs that degrade extracellular matrix components critical for healing.[12]

Surgical Technique

The surgical technique also plays a pivotal role. Poorly performed wound closure techniques that result in excessive tension or improper suture placement can lead to wound dehiscence, ischemia, and suboptimal healing. Excessive tension at the wound edges can cause tissue ischemia by compressing blood vessels and reducing perfusion, while improper suture techniques can lead to tissue necrosis and wound dehiscence (see Image. Surgical Wound Dehiscence). Similarly, failure to minimize wound tension during closure increases the risk of scar contracture, tissue ischemia, and impaired wound healing, highlighting the importance of using tension-reducing techniques such as tension-relieving sutures and surgical flaps.[13]

Postoperative Care

Postoperative care is equally essential for facilitating optimal wound healing outcomes. Poor wound hygiene, characterized by inappropriate wound care practices that include improper cleansing and dressing changes and inadequate wound protection from trauma, can increase the risk of infection and disrupt the healing environment. Inadequate cleansing can leave behind debris and bacteria that may trigger inflammatory responses. Improper dressing changes can either desiccate the wound or create an overly moist environment, both detrimental to healing.

Meanwhile, prolonged immobilization or restricted mobility can impair blood flow and tissue oxygenation, hindering the healing process and increasing the risk of complications such as venous stasis and pressure ulcers. Therefore, comprehensive postoperative care protocols focusing on wound hygiene, proper dressing techniques, and mobilization strategies are essential for promoting timely and effective wound healing following MMS. Mobilization strategies encourage circulation and lymphatic drainage, which are essential for delivering nutrients and removing waste products from the healing tissue.[14]

By incorporating these considerations into patient care, healthcare providers can significantly enhance wound healing outcomes and reduce the incidence of postoperative complications.

Clinical Significance

A comprehensive clinical approach encompassing various strategies may be employed to optimize wound healing following MMS. This multifaceted approach involves preoperative assessment, meticulous surgical technique, comprehensive postoperative care, and tailored interventions based on individual patient needs.

Preoperative Assessment and Patient Education

A thorough preoperative assessment is essential before surgery. Evaluating patient factors such as age, comorbidities, and smoking status allows for risk stratification and tailored interventions. For example, older patients typically have decreased dermal collagen content and reduced fibroblast activity, necessitating closer postoperative monitoring and possible use of adjunctive therapies to enhance healing. In patients with diabetes, assessing glycemic control by obtaining presurgical HbA1c levels helps predict potential healing delays and allows preoperative optimization of blood glucose levels to mitigate these risks.[15] 

Patient education regarding wound care expectations and adherence to postoperative instructions is likewise crucial.[16] Educating patients on the importance of proper wound care, such as maintaining a moist wound environment and avoiding mechanical stress on the wound site, can improve patient compliance and satisfaction. Providing detailed instructions on postoperative wound care, signs of infection, and the impact of lifestyle modifications, such as smoking cessation and nutritional optimization, can further enhance healing outcomes.[17] This education may include a demonstration of proper wound-cleaning techniques and a discussion of the impact of dietary choices on wound healing, emphasizing the dependence of tissue repair on adequate levels of proteins, vitamins, and minerals.[18]

Surgical Technique and Wound Closure

Meticulous surgical technique is paramount for promoting optimal wound healing outcomes. Good surgical execution includes minimizing tissue trauma, achieving hemostasis, and utilizing tissue-sparing approaches whenever possible. Techniques such as precise excision with minimal margin clearance while ensuring complete tumor removal help preserve surrounding healthy tissue and reduce the extent of required wound healing. Achieving hemostasis is critical to prevent hematoma formation, which can impede the healing process by creating a nidus of infection and promoting inflammation.[19]

Careful consideration should also be given to wound closure methods, ensuring adequate approximation without excessive tension. Techniques such as layered closure or tension-reducing sutures can help minimize wound tension and facilitate primary intention healing. Layered closure involves suturing the subcutaneous tissue separately from the dermis and epidermis, which distributes tension more evenly and promotes better alignment of collagen fibers during healing. The use of tension-relieving techniques, such as Z-plasty or V-Y advancement flaps, may also be beneficial in areas of high tension.[20]

Additionally, the use of skin substitute grafts has emerged as a valuable adjunctive therapy that promotes secondary intention healing in cases where primary closure is not feasible. Skin substitutes, such as acellular dermal matrices and bioengineered skin constructs, provide a scaffold for cellular ingrowth and promote wound contraction, ultimately expediting the healing process. These substitutes support the migration of keratinocytes and fibroblasts, enhancing reepithelialization and extracellular matrix formation.[21]

Postoperative Wound Care

Proper wound care in the postoperative period plays a significant role in facilitating wound healing. Dressings must be selected based on wound characteristics to help maintain a moist wound environment conducive to healing.[22] Advanced dressings, such as silicone-based dressings or hydrocolloids, create a moist environment that supports wound healing and reduces the risk of hypertrophic scarring (see Image. Hypertrophic Scar Formation). These dressings maintain optimal hydration, facilitate autolytic debridement, and protect against bacterial contamination.[23] 

Educating patients on gentle cleansing techniques and providing instructions for pain management are other essential components of postoperative care. Gentle cleansing with noncytotoxic solutions helps remove debris and reduce the risk of infection without impairing cellular activity. Proper pain management is essential to reduce stress-induced cortisol release, which can impede wound healing.[24] Regular wound assessment and monitoring for signs of infection or other complications, such as increased erythema, purulent discharge, and delayed healing, are essential for early intervention.[25]

Addressing Complications and Risk Factors

Prompt identification and management of complications, such as infection and hematoma, are critical for preventing delays in wound healing. Infection management involves appropriate antibiotic use, necrotic tissue debridement, and maintenance of an optimal wound environment (see Image. Surgical Wound Infection). Hematoma evacuation is necessary to prevent pressure-induced ischemia and promote normal healing dynamics. Moreover, addressing modifiable risk factors, such as smoking and nutritional status, can improve healing outcomes significantly. Collaboration with other healthcare professionals, such as wound care specialists and nutritionists, may be necessary to address these factors comprehensively. Ensuring adequate protein, vitamin C, and zinc intake is crucial for collagen synthesis and immune function.

Utilization of Adjunctive Therapies

Adjunctive therapies may be employed to enhance wound healing in select cases. Negative pressure wound therapy (NPWT) promotes granulation tissue formation and wound contraction, particularly in complex wounds.[26] NPWT increases local blood flow, reduces edema, and removes exudates, creating an environment conducive to healing. Similarly, hyperbaric oxygen therapy (HBOT) improves tissue oxygenation and accelerates wound healing in patients with compromised vascularity. HBOT enhances fibroblast proliferation, collagen synthesis, and angiogenesis, providing an adjunctive benefit in ischemic or nonhealing wounds.[27] These adjunctive therapies can be valuable additions to standard wound care protocols, especially in cases of complex wounds and compromised tissue viability.

By integrating these strategies into clinical practice, healthcare providers can optimize wound healing outcomes following cutaneous surgery, leading to improved patient satisfaction and reduced complications. Continued research and innovation in wound management are essential for advancing the field and further improving patient outcomes. The development of novel biomaterials, growth factor therapies, and regenerative medicine approaches holds promise for future advancements in wound healing post-MMS.

Enhancing Healthcare Team Outcomes

Effective coordination within an interprofessional healthcare team is paramount for enhancing patient outcomes following MMS. This collaborative approach involves close communication and coordination among various healthcare professionals, including dermatologists, primary care providers, nurses, medical assistants, wound care specialists, and nutritionists, among others. Dermatologists play a central role in surgical decision-making and wound assessment, while nurses and medical assistants oversee postoperative wound care and monitor for complications.[28] Wound care specialists provide expertise in advanced wound management techniques, such as NPWT and hyperbaric oxygen therapy, which may be indicated for complex or compromised wounds.

Nutritionists play a critical role in optimizing patients' nutritional status, which is essential for supporting wound healing and tissue repair. Primary care physicians are integral members of the interdisciplinary team, assisting in managing comorbidities such as diabetes and hypertension, which can impact wound healing, and providing support for the cessation of smoking, a modifiable risk factor associated with delayed healing. Through collaboration and shared decision-making, the interprofessional healthcare team can ensure comprehensive and holistic care tailored to individual patient needs, ultimately leading to improved wound healing outcomes and enhanced patient satisfaction.