Wound Healing & Wound Care

Souvik Adhikari

Postdoctoral Trainee

DEFINITION Response of an organism to a physical

disruption of a tissue/organ with an aim to repair or reconstitute the defect and to re-establish homeostasis.

Can be achieved by 2 processes: scar formation & tissue regeneration.

Dynamic balance between these 2 is different in different tissues.

Introduction During healing, a complex cascade of

cellular events occur to achieve resurfacing, reconstitution and restoration of tensile strength of injured tissue.

3 classic but overlapping phases occur: inflammation, proliferation & maturation.

Early Wound Healing Events (Days 1-4)

Stages of Wound Healing

Inflammatory Phase Blood vessels are disrupted, resulting in

bleeding. Hemostasis is achieved by formation of platelet plug & activation of extrinsic & intrinsic clotting pathways.

Formation of a provisional fibrin matrix. Recruitment of inflammatory cells into the

wound by potent chemoattractants.

Early Events in Inflammation Fibrin and fibronectin form a lattice that provides

scaffold for migration of inflammatory, endothelial, and mesenchymal cells.

Neutrophilic infiltrate appears: removes dead tissue & prevent infection.

Monocytes/macrophages follow neutrophils: orchestrated production of growth factors & phagocytosis.

Late Events in Inflammation Entry of lymphocytes. Appearance of mast cell: aberrant scarring?

Intermediate Events (Days 4-21)

Proliferative Phase Granulation tissue formation (composed of

fibroblasts, macrophages and emdothelial cells).

Contraction. Re-epithelialization (begins immediately

after injury)

Mesenchymal cell proliferation Fibroblasts are the major mesenchymal

cells involved in wound healing, although smooth muscle cells are also involved.

Macrophage products are chemotactic for fibroblasts. PDGF, EGF, TGF, IL-1, lymphocytes are as well.

Replacement of provisional fibrin matrix with type III collagen.

Angiogenesis Angiogenesis reconstructs vasculature in areas

damaged by wounding, stimulated by high lactate levels, acidic pH, decreased O2 tension in tissues.

Recruitment & assembly of bone marrow derived progenitor cells by cytokines is the central theme.

FGF-1 is most potent angiogenic stimulant identified. Heparin important as cofactor, TGF-alpha, beta, prostaglandins also stimulate.

Epithelialization Basal cell layer thickening, elongation,

detachment & migration via interaction with ECM proteins via integrin mediators.

Generation of a provisional BM which includes fibronectin, collagens type 1 and 5.

Epithelial cells proliferation contributes new cells to the monolayer. Contact inhibition when edges come together.

Late Wound Healing Events (Days 21-1 yr)

Remodeling Phase Programmed regression of blood vessels &

granulation tissue. Wound contraction. Collagen remodeling.

Collagen 19 types identified. Type 1(80-90%) most

common, found in all tissue. The primary collagen in a healed wound.

Type 3(10-20%) seen in early phases of wound healing. Type V smooth muscle, Types 2,11 cartilage, Type 4 in BM.

Wound Contraction Begins approximately 4-5 days after

wounding by action of myofibroblasts. Represents centripetal movement of the

wound edge towards the center of the wound.

Maximal contraction occurs for 12-15 days, although it will continue longer if wound remains open.

Wound Contraction The wound edges move toward each other

at an average rate of 0.6 to .75 mm/day. Wound contraction depends on laxity of

tissues, so a buttock wound will contract faster than a wound on the scalp or pretibial area.

Wound shape also a factor, square is faster than circular.

Wound Contraction Contraction of a wound across a joint can

cause contracture. Can be limited by skin grafts, full better

than split thickness. The earlier the graft the less contraction. Splints temporarily slow contraction.

Remodeling After 21 days, net accumulation of

collagen becomes stable. Bursting strength is only 15% of normal at this point. Remodeling dramatically increases this.

3-6 weeks after wounding greatest rate of increase, so at 6 weeks we are at 80% to 90% of eventual strength and at 6months 90% of skin breaking strength.

Remodeling The number of intra and intermolecular cross-

links between collagen fibers increases dramatically.

A major contributor to the increase in wound breaking strength.

Quantity of Type 3 collagen decreases replaced by Type 1 collagen

Remodeling continues for 12 mos, so scar revision should not be done prematurely.

Disturbances in Wound Healing

Local Factors Infection: impairs healing. Smoking: increased platelet adhesiveness,

decreased O2 carrying capacity of blood, abnormal collagen.

Radiation: endarteritis, abnormal fibroblasts.

Systemic Factors Malnutrition Cancer Old Age Diabetes- impaired neutrophil chemotaxis,

phagocytosis. Steroids and immunosuppression suppresses

macrophage migration, fibroblast proliferation, collagen accumulation, and angiogenesis. Reversed by Vitamin A 25,000 IU per day.

Abnormal Response to Injury

Inadequate Regeneration CNS injuries Bone nonunion Corneal ulcers

Inadequate Scar Formation Diabetic foot ulcers. Sacral pressure sores. Venous stasis ulcers.

Excessive Regeneration Neuroma Hyperkeratosis in cutaneous psoriasis Adenomatous polyp formation.

Excessive Scar Formation Excessive healing results in a raised, thickened

scar, with both functional and cosmetic complications.

If it stays within margins of wound it is hypertrophic. Keloids extend beyond the confines of the original injury.

Dark skinned, ages of 2-40. Wound in the presternal or deltoid area, wounds that cross langerhans lines.

Keloids and Hypertrophic Scars Keloids more familial Hypertrophic scars develop soon after

injury, keloids up to a year later. Hypertrophic scars may subside in time,

keloids rarely do. Hypertrophic scars more likely to cause

contracture over joint surface.

Keloids and Hypertrophic Scars Both from an overall increase in the

quantity of collagen synthesized. Recent evidence suggests that the

fibroblasts within keloids are different from those within normal dermis in terms of their responsiveness.

No modality of treatment is predictably effective for these lesions.

Wound Care

Basics Optimize systemic parameters Debride nonviable tissue Reduce wound bioburden Optimize blood flow Reduce edema Use dressings appropriately Use pharmacologic therapy Close wounds with grafts/flaps as indicated

Optimize systemic parameters Age: cannot be reversed, usage of growth

factors, aggressive optimization of systemic parameters & supplementation.

Avoidance of ischemia & malnutrition. Correction of diabetes, removal of FB. Avoidance of steroids, alcohol, smoking. Avoidance of reperfusion injury: total

contact casting, compression therapy.

Debridement & Reduction of Bioburden Surface irrigation with saline. Debridement: surgical, enzymatic (papain with

urea, collagenase), mechanical (pressurized water jet), autolytic, maggots.

Antibiotics: cellulitis, decreased rate of healing, increased pain, straw colored oozing from skin, contaminated wounds, mechanical implants.

Removal of FB.

Optimize blood flow & oxygen supply Warmth Hydration Surgical revascularization Hyperbaric O2 therapy: limb salvage.

Reduce edema Elevation Compression Negative pressure wound therapy: removes

pericellular transudate & wound exudate as well as deleterious enzymes. Cannot be used in ischemic, badly infected or inadequately debrided wounds or in malignancy.

Dressings Absorption characteristics: none – films, low –

hydrogels, moderate - hydrocolloids, high – foams, alginates, collagen.

Hydrogels (eg. starch) rehydrate wounds (benefit in small amounts of eschar, infected wounds).

Hydrocolloids promote wound debridement by autolysis.

Antimicrobial dressings: silver, cadexomer iodine, mupirocin, neomycin.

Skin Substitutes Autologous keratinocyte sheets. Biobrane Oasis Alloderm Integra (sites prone to contracture, coverage of

tendons, bone, surgical hardware) TransCyte Dermagraft Orcel

Pharmacologic therapy Antimicrobials PDGF EGF VEGF Vit A: steroid use Absolutely of no use in normally healing

wounds

Flaps & Grafts Radiation wounds require flaps. Chronic nonhealing ulcers. Extensive areas of ulceration. Major soft tissue loss. Other therapies: electrical stimulation for

recalcitrant ulcers.

Recent Developments Manuka honey (apitherapy) in venous leg

ulcers. Hyperbranched polyglycerol electrospun

nanofibers. Androstenediol in steroid inhibited healing. GM-CSF hydrogel in deep 2nd deg burns. LASER therapy enhances tissue repair? Nitric oxide containing nanoparticles.