> Wound healing occurs in 3 phases: inflammatory, fibroproliferative, and maturation/ remodeling ## Types of Wound Healing - Primary - wound closed by reapproximating the edges - Delayed primary - debriding subacute or chronic wound , followed by primary closure (comparable to primary healing > Debridement removes inflammatory mediators and senescent cells to resolves prolonged inflammation and reset wound healing to the acute phase. - Secondary - wound allowed to heal on its own by [[contraction]] and [[epithelialization]] ## 3 Phases of Wound Healing ^[Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. _Nature_. 2008;453(7193):314-321. doi:[10.1038/nature07039](https://doi.org/10.1038/nature07039)] ### 0. Hemostasis (Seconds) 1. Vasoconstriction and coagulation to limit bleeding - Hematomas compromise a closed wound by: - (1) ↗ tension → (2) ↘ perfusion to overlying soft tissue - (3) serving as a nidus for infection - (4) prolonging inflammation > Technical finesse: > - Precede closure with meticulous hemostasis using electrocautery that must also balance excess use and thermal injury > → use lower power precise strike when possible > → skip cautery when possible: e.g. dermal bleeding stops after reapproximation > - Hemostatic closure with simple running, interlocking running, and horizontal mattress sutures > - risks ischemia and necrosis ### I. Inflammatory (Days 1-6) 1. Vasodilation, ↗ permeability, chemotaxis, cellular migration and response to fight pathogens and to remodel - Most critical to healing: macrophages (days 2-4) regulate growth factors >A chronic wound manifests with prolonged inflammation, when the wound failed to move to the fibroproliferative phase:^[Janis JE, Kwon RK, Lalonde DH. A practical guide to wound healing. _Plast Reconstr Surg_. 2010;125(6):230e-244e. doi:[10.1097/PRS.0b013e3181d9a0d1](https://doi.org/10.1097/PRS.0b013e3181d9a0d1)] >→ Technical finesse: >- Minimize crush injury to minimize inflammation (ie used toothed forceps, with delicate handling) >- Do not close inflammed tissue primarily >- Manage edema to optimize cell signaling and migration ### II. Fibroproliferative (Day 4 - Week 3) 1. Matrix formation - Fibroblasts (immigration starting days 2-3) start making [[collagen]] day 5 ⇒ tensile strength ↗ on days 4-5 2. Angiogenesis 3. [[Epithelialization]] > Technical finesse: > - Use enough sutures to offload tension and secure wound edges without creating too many points of strangulations (impairing perfusion and oxygenation), esp at the tip ### III. Maturation/ Remodeling (Week 3 - 1 Year) - [[Collagen]] quantity peaks (week 3-5), followed by organization and cross-linking, with type 1 collage replacing type III collagen (4:1 ratio) to improve tensile strength - ⇒ Tensile strength: 3% at 1 week, *30% at 3 weeks, 80% at 3 months*^[Janis JE, Harrison B. Wound Healing: Part I. Basic Science. _Plast Reconstr Surg_. 2016;138(3 Suppl):9S-17S. doi:[10.1097/PRS.0000000000002773](https://doi.org/10.1097/PRS.0000000000002773)] - Healed tissue never restore 100% of preinjury strength^[Buchanan PJ, Kung TA, Cederna PS. Evidence-based medicine: Wound closure. _Plast Reconstr Surg_. 2014;134(6):1391-1404. doi:[10.1097/PRS.0000000000000720](https://doi.org/10.1097/PRS.0000000000000720)] - ↘ glycosamnoglycans, water content, vascularity, and cellular population > - Timing of postoperative physical activity and suture (half life) selection depend on the growth of tensile strength of the wound, which correlates with matrix remodeling and collagen deposition > - Older patients take more time to heal, and healing has lower tensile strength ⇒ consider leaving epidermal sutures in longer for elderly patients - Timing for suture removal based on location: ![[Pasted image 20250119113216.png]] #### Fetal healing - During the first 2 trimesters, wound may heal without any [[Scars]] - There's a higher concentrations of type III collagen and hyaluronic acid; no inflammation, no angiogenesis, relative hypoxia ## Factors affecting wound healing → listed in order of how quickly they can be modified ### Local factors - Enhanced with: - O2 delivery - needs good enough cardiac output, distal perfusion, RBCs, and oxygen dissociation (pH) - worsens with atherosclerosis, Raynaud's disease, scleroderma - Hyperbaric oxygen ↗ angiogenesis and fibroblasts recruitment - Moisture - ↗ [[Epithelialization]] - Warmth - ↗ perfusion and tensile strength - Worsened with: - Infection - typical clinical infection (free floating bacteria): ↘ O2 tension, ↘ pH, ↗ collagenase, ↘ epithelialization and angiogenesis, ↗ inflammation and edema - biofilm formation (bacteria in an extracellular polymeric substance): bacteria evades typical culture, immune response, and antimicrobials - often grow on prosthetic implants or microcolony within soft tissues - degrade soft tissue and break down the skin barrier - Radiation therapy - damage small vessels, fibroblasts, and DNA (slowing [[Epithelialization]] and its strength) - Free radicals > Poor O2 delivery and infections are the 2 most common causes of poor wound healing ### Drugs - Cigarette smoking - Nicotine constricts blood vessels and ↗ platelet adhesiveness - Carbon monoxide binds to hemoglobin and reduces oxygen delivery - Hydrogen cyanide inhibits oxygen transport > Smoking cessation should occur 4 weeks prior to any elective operation. Consider preoperative urine cotinine testing. - Steroids - ↘ inflammation, inhibit epithelialization, and reduce collagen production > Chronic steroid use thins the dermis, making skin more susceptible to wounding, more difficult for suture or grafting, and more easily damaged by adhesives used for wound care. - Antineoplastic Agents - few or no adverse effects if administration is delayed for 10 to 14 days after wound closure ^[Falcone RE, Nappi JF. Chemotherapy and wound healing. _Surg Clin North Am_. 1984;64(4):779-794. doi:[10.1016/s0039-6109(16)43394-3](https://doi.org/10.1016/s0039-6109(16)43394-3)] - Anti-inflammatories - may ↘ collagen synthesis - Lathyrogens - prevent cross-linking of collagen, which decreases tensile strength - e.g. Beta-aminopropionitrile (BAPN), a product of ground peas and D-penicillamine - possible therapeutic use for decreasing scar tissue ### Vitamin Deficiencies - Vitamin A - Reverses delayed wound healing from steroids, though it has no effect for those with immunosuppression - Treatment options: - Oral: 25,000 IU once per day increases tensile strength - Topical: 200,000 IU every 8 hours increases epithelialization - Vitamin C - Vital for hydroxylation reactions in collagen synthesis - Deficiency leads to scurvy - Vitamin E - Functions as an antioxidant and stabilizes membranes (**unproven to reduce scarring**) - Large doses inhibit healing and may cause dermatitis - Vitamin D - Receptor is required for normal macrophage response and epithelial regeneration - Zinc - Serves as a cofactor for many enzymes - Deficiency results in impaired epithelial and fibroblast proliferation ### Comorbidities - Diabetes - Atherosclerotic disease - Immunodeficiency (worsen inflammatory response and repair recruitment) - Renal failure - Nutritional deficiencies ### Genetics - Predisposition to [[Scars#Hypertrophic scars (HTS)]] and [[Scars#Keloid scars]] - [[Genetics Disorders of the Skin]] - Skin type: Pigmentation (Fitzpatrick type), elasticity, thickness, sebaceous quality, and location (e.g., shoulder, sternum, earlobe) - Worse with age ^[Sgonc R, Gruber J. Age-related aspects of cutaneous wound healing: a mini-review. _Gerontology_. 2013;59(2):159-164. doi:[10.1159/000342344](https://doi.org/10.1159/000342344)] ## Scarring → Discussed here: [[Scars]] > [[Wound Closure]] depends on tissue location, tension, integrity, and other characteristics in addition to desired hemostasis, repair, and maintenance level. #basicscience #clinicalscience