1.Wound Healing & Wound Care Souvik Adhikari Postdoctoral Trainee

2. 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.

3. 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.

4. Early Wound Healing Events (Days 1-4) 5. Stages of Wound Healing 6. 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.

7. 8. 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.

9. 10. 11. 12. 13. Late Events in Inflammation

Entry of lymphocytes.

Appearance of mast cell: aberrant scarring?

14. Intermediate Events (Days 4-21) 15. Proliferative Phase

Granulation tissue formation (composed of fibroblasts, macrophages and emdothelial cells).

Contraction.

Re-epithelialization (begins immediately after injury)

16. 17. 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.

18. 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.

19. 20. 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.

21. 22. Late Wound Healing Events (Days 21-1 yr) 23. Remodeling Phase

Programmed regression of blood vessels & granulation tissue.

Wound contraction.

Collagen remodeling.

24. 25. 26. 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.

27. 28. 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.

29. 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.

30. 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.

31. 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.

32. 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.

33. 34. Disturbances in Wound Healing 35. Local Factors

Infection: impairs healing.

Smoking: increased platelet adhesiveness, decreased O2 carrying capacity of blood, abnormal collagen.

Radiation: endarteritis, abnormal fibroblasts.

36. 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.

37. Abnormal Response to Injury 38. Inadequate Regeneration

CNS injuries

Bone nonunion

Corneal ulcers

39. Inadequate Scar Formation

Diabetic foot ulcers.

Sacral pressure sores.

Venous stasis ulcers.

40. Excessive Regeneration

Neuroma

Hyperkeratosis in cutaneous psoriasis

Adenomatous polyp formation.

41. 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.

42. 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.

43. 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.

44. Wound Care 45. 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

46. 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.

47. 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.

48. Optimize blood flow & oxygen supply

Warmth

Hydration

Surgical revascularization

Hyperbaric O2 therapy: limb salvage.

49. 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.

50. 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.

51. Skin Substitutes

Autologous keratinocyte sheets.

Biobrane

Oasis

Alloderm

Integra (sites prone to contracture, coverage of tendons, bone, surgical hardware)

TransCyte

Dermagraft

Orcel

52. Pharmacologic therapy

Antimicrobials

PDGF

EGF

VEGF

Vit A: steroid use

Absolutely of no use in normally healing wounds

53. Flaps & Grafts

Radiation wounds require flaps.

Chronic nonhealing ulcers.

Extensive areas of ulceration.

Major soft tissue loss.

Other therapies: electrical stimulation for recalcitrant ulcers.

54. Recent Developments

Manuka honey (apitherapy) in venous leg ulcers.

Hyperbranched polyglycerol electrospun nanofibers.

Androstenediol in steroid inhibited healing.

GM-CSF hydrogel in deep 2 nddeg burns.

LASER therapy enhances tissue repair?

Nitric oxide containing nanoparticles.

55. THANK YOU