WOUND HEALING

“ God heals, and the doctor takes the fees ”

Benjamin Franklin(American Statesman, scientist, Philosopher)

Phases of Healing Inflammatory (Reactive) Haemostasis Inflammation

Proliferative (Regenerative/Reparative) Epithelial migration proliferation Maturation

Maturational (Remodeling) Contraction scarring Remodeling

Cutaneous Wound Healing

1. By Primary Intention

2. By Secondary Intention

3. By Tertiary Intention

Secondary Union differs from Primary Union by:

Larger clot or scab rich in fibrin or fibronectin

More intense inflammation

Much larger amounts of granulation tissue formed

Involves wound contraction

Factors affecting Wound Healing

Infection Nutrition ( proteins, vit.C, vit.A, Zn, Fe) Steroids / Adriamycin Mechanical factors (a) Increased pressure/torsion) (b) Ischemia Malnutrition Advanced age Ionising Radiation Diabetes Mellitus

Growth Factors affecting Wound

Healing at Different Stages

Epithelial Proliferation: EGF TGFa KGF HGFMonocyte chemotaxis: PDGF FGF TGFbFibroblast Migration: PDGF FGF TGFbFibroblast Proliferation: PDGF FGF EGF TNFAngiogenesis: VEGF Ang FGFCollagen Synthesis: TGFb PDGFCollagen secretion: PDGF FGF EGF TNF TGFb inhibits

Growth Factors in Wound Healing Increase size of cells

Increase number of cells

Inhibit apoptosis

Pleiotropic effects i.e initiate cell proliferation, migration, differentiation, contractility, enhance synthesis of specialized proteins eg. Collagen in fibroblasts

Act in autocrine, paracrine, or endocrine manner

STEM CELLSHomeostatic relation between replication and

differentiation of stem cellsCells differentiate progressively as they migrate into the

upper layers of the epitheliumIn the skin stem cell niches are in the basal layer

Characteristics of Stem cells 1. Self renewal capacity2. Asymmetric replication.

Regenerative MedicineRegenerative MedicineGoal: Goal: Regeneration and repopulation of damaged organ

using embryonic or adult stem cells.

Therapeutic CloningTherapeutic Cloning Patients cell Enucleated oocyte

Nuclear transfer embryo

Nuclear transfer blastocyst

Embryonic stem cells

Blood cells Neurons Muscle cells

Potential Therapeutic Strategies

1. Transplanting stem cells into area of injury

2. Use of stem cell systems to produce large amounts of differentiated cells for transplantation

Repair By Connective Tissue includes: Angiogenesis 1. Vasculogenesis 2. Angiogenesis)

Deposition of ECM

Migration and Proliferation of Fibroblasts

Maturation and Reorganisation of Fibrous Tissue.

Fetal Wound Healing Younger the fetus less noticeable is the scar Fetal fibroblasts even in adult transplantation heals with the

absence of inflammation Theory: that wound fibroblasts do not become myofibroblasts

until late in gestation. IL6 is high in adult stimulated fibroblasts compared to fetal

stimulated ones with coincides with increased inflammation in adults

Thrombospondin 1 decreases with increase in gestation. It destabilizes matrix contracts in the EC space, facilitates mitogenesis and chemotaxis. Promotes cell associated protease and self supports matrix turnover. Thus inflammation would decrease and there would be less scarring

Aberrations of HealingAberrations of Healing

Keloids: Females>Males Blacks>Whites/ Familial Outgrows the wound Rarely subsides leads to pathologic scarring

in other areas of the body. In bones-

Osteoarthritis common on the face

shoulders back and sternum

Hypertrophic Scar Females=Males Not race related/ familial Remains within the wound Subsides with time

Flexor surfaces affected

1.compression bandages

2. intralesional Triamcinolone

3. Excision and skin grafting

4. Laser

5. Surgery f/b post op interstitial

radiotherapy

Excessive granulation tissue which protrudes above the level of the skin & hinders re epithelialisation is called “EXUBERANT GRANULATION or PROUD FLESH! Rx: Cautrise or surgically resect the tissue

Rx of Aberrations

Keloid Hypertrophic scar

Newer Concepts

Low level laser therapy.

Negative pressure wound therapy(NPWT).

Collagen & chondroitin sulphate : Integra

Apligraftrade: skin substitute containing collagen and seeded cells

Alloderm: immunologically inert, nonliving, allogenic, acellular dermal matrix with intact basement membrane prepares wound bed for grafting

Tegaderm

Used for simple shallow wound dressing Protects from water loss mechanical injury and drying

TransCyte (ECM matrix generated by allogenic human dermal fibroblasts serves as a matrix for neodermis generation

ORCEL: Composite cultured skin. Fibroblasts, keratinocytes seeded on opposite sides of bilayered matrix of bovine collagen

Dermagraft living allogenic dermal fibroblasts grown on a degradable scaffold. Good resistance to tearing

E-Z Derm

Biosynthetic porcine derived xenograft

Collagen has been crosslinked with aldehyde

Can be conveniently stored at room temperature

long shelf life. 

perforated or non-perforated

Partial thickness, donor sites, sandwich autografts, and to cover full thickness wounds prior to grafting.

OASIS

comprised of small intestine submucosa acellular collagen matrix. Chance of rejection

OPSITE

beta-Glucan stimulates the macrophage activity and promotes rapid wound healing.

Beta-Glucan Collagen mesh or Glucan II (Beta-Glucan) mesh. . Rapid healing without dressing changes painless treatment.

HONEYSOFT

Natural dressingHoney-impregnated dressing Chronic unhealing wounds. Impregnated into a compress of EVA (ethylenevinylacetate) mesh

Honey cleans the wound without disturbing it Removing the dressing causes no damage no known side effects

Hyperbaric Medicine Systemic delivery of oxygen to the tissues

unit which has been compressed to approximately 2-2.4 ATA.

Stimulates angiogenesis and fibroblast migration, enhances neutrophil and antibiotic killing action, and suppresses alpha toxin production in gas gangrene.

Total Contact Casting A treatment used for successful offweighting of

plantar foot ulcerations.

Provides decreased plantar surface pressures over wounded areas of the foot, by redistributing weight bearing over the entire lower leg.

a novel hydrogel, to seal wounds and at the same time deliver an antibacterial

punch

"They're like rebar when you're building

something with concrete,

They give the cement something to hang

onto."

"MAX8,"

encapsulate living cells in the

hydrogel and then inject the gel into secondary sites without harming

the cells.