Wound HealingWound Healing

The Basic PrinciplesThe Basic Principles

Wound healingWound healing

Day 21 - 2yrsDay 21 - 2yrsRemodellingRemodelling

ContractureContracture

Day 4 - 21Day 4 - 21ProliferationProliferation

GranulationGranulation

Day 1 - 4Day 1 - 4InflammationInflammation

ImmediateImmediateHaemostasisHaemostasis

Days post injuryDays post injuryPhase of healingPhase of healing

HaemostasisHaemostasis

Sealing of damaged blood vesselsSealing of damaged blood vessels VasoconstrictionVasoconstriction Platelet –utility worker Platelet –utility worker Under the influence of the ADP, Under the influence of the ADP,

platelets aggregate and adhere to platelets aggregate and adhere to the exposed collagen. Intrinsic the exposed collagen. Intrinsic clotting cascade clotting cascade → thrombin → → thrombin → fibrinogen →fibrin → platelet fibrinogen →fibrin → platelet aggregate into a stable aggregate into a stable haemostatic plug haemostatic plug

Inflammatory phaseInflammatory phase Characterised by “ rubor et tumor cum Characterised by “ rubor et tumor cum

calore et dolore” – 4 days.calore et dolore” – 4 days. Polymorphonuclear leukocytes - non Polymorphonuclear leukocytes - non

skilled laborers – phagocytize debri skilled laborers – phagocytize debri and microorganisms, aided by local and microorganisms, aided by local mast cells.mast cells.

Macrophages – contractor – Macrophages – contractor – phagocytize bacteria –second line of phagocytize bacteria –second line of defence and secrete IMs and growth defence and secrete IMs and growth factors like FGF,EGF,TGF beta, IL-1 factors like FGF,EGF,TGF beta, IL-1 which appears to direct the next stage.which appears to direct the next stage.

Proliferative phase (4 – 21 Proliferative phase (4 – 21 days)days)

Involves proliferation, granulation Involves proliferation, granulation and contractionand contraction

Framers build the framework of the Framers build the framework of the new house – “framer” cells – new house – “framer” cells – fibroblasts secrete collagen network – fibroblasts secrete collagen network – specialised fibroblasts specialised fibroblasts → wound → wound contractioncontraction

The “plumber” cells , pericytes and The “plumber” cells , pericytes and endothelial cells → angiogenesisendothelial cells → angiogenesis

The “roofer” and “sider”cells - The “roofer” and “sider”cells - keratinocytes → epithelisationkeratinocytes → epithelisation

Remodelling or Maturation Remodelling or Maturation phasephase

Interior finishing Interior finishing ΞΞ Remodeling or Remodeling or Maturation → ↑Tensile strengthMaturation → ↑Tensile strength

The cell → fibroblastThe cell → fibroblast Results in scar – active dynamic tissueResults in scar – active dynamic tissue

Stage I (upto 4 wks) – soft, fine&weakStage I (upto 4 wks) – soft, fine&weak

Stage II (4 – 12 wks)–red, hard & Stage II (4 – 12 wks)–red, hard & strongstrong

Stage III (12wks to 2 yrs) – soft, Stage III (12wks to 2 yrs) – soft, white& supple scarwhite& supple scar

PlateletsPlatelets

Vessel damageVessel damage

Platelet aggregationPlatelet aggregation

Activation of coagulation cascadeActivation of coagulation cascade

ClotClot

DegranulationDegranulation Inflammatory Inflammatory mediatorsmediators

NeutrophilsNeutrophils

AdhesionAdhesion DiapedesisDiapedesis Migration by chaemotaxisMigration by chaemotaxis Phagocytose bacteriaPhagocytose bacteria Scavenge necrotic debris and Scavenge necrotic debris and

foreign materialforeign material

MonocytesMonocytes

Monocyte Monocyte MACROPHAGEMACROPHAGE

Phagocytose bacteriaPhagocytose bacteria Release of cytokinesRelease of cytokines Degradation of connective tissueDegradation of connective tissue Stimulate angiogenesisStimulate angiogenesis

Inflammatory phase Inflammatory phase Reparative Reparative phasephase

LymphocytesLymphocytes

Helper T cellsHelper T cells Produce chaemotactic factors likeProduce chaemotactic factors like

IFN –r, IL – 2, CSFIFN –r, IL – 2, CSF Involved in chronic wound healingInvolved in chronic wound healing

FibroblastFibroblast

SynthesizeSynthesize CollagenCollagen FibronectinFibronectin Protein Protein

FibroblastFibroblast Myofibroblast Myofibroblast ContractionContraction

Extracellular matrix

AngiocytesAngiocytes

Proliferation of endothelial cellsProliferation of endothelial cells

Formation of capillary budsFormation of capillary buds

AngiogenesisAngiogenesis

KeratinocytesKeratinocytes

MigrationMigration Resurface the Resurface the woundwound

PhagocytosisPhagocytosis Cytokine releaseCytokine release Reconstitution of basement Reconstitution of basement

membranemembrane Collagen secretionCollagen secretion Anchoring Anchoring

fibrilsfibrils

Healing responsesHealing responsesHaemostsis

Inflammation

Proliferation

Immediate

Day 1 - 4

Day 4 - 21

Platelets

Neutrophils

Macrophages

Lymphocyte

FibroblastFramersContracture

Angiocyte Plumber

Keratinocytes Roofers & siders

Utility worker

Unskilled workers

Contractor

Asst. Contractor

Remodeling Day 21–2 yrs Fibrocytes Remodelers

MatrixMatrix

Formation of fibrin plug marks the Formation of fibrin plug marks the first stage of tissue repair first stage of tissue repair

It serves as a provisional matrix It serves as a provisional matrix

Provisional matrix replaced by Provisional matrix replaced by mature matrix during proliferative mature matrix during proliferative phasephase

Matrix contd.Matrix contd.

Matrix is composed of Matrix is composed of Fibrous proteinFibrous proteinPolysaccharide gelPolysaccharide gel

ProteoglycansProteoglycansFunctionFunction

Permits difussion of nutrients to Permits difussion of nutrients to the cellsthe cells

Matrix contd.Matrix contd.

Fibrous protein has two partsFibrous protein has two parts

Structural part formed by collagen & Structural part formed by collagen & elastinelastin

Adhesive part formed by fibronectin and Adhesive part formed by fibronectin and laminin laminin

FibronectinFibronectin

Linear glycoproteins with modular Linear glycoproteins with modular cell/matrix binding structurecell/matrix binding structure

This structure encourages cell to cell This structure encourages cell to cell & cell to substrate interaction& cell to substrate interaction

Fibronectin and its degradation Fibronectin and its degradation products are chemo attractantproducts are chemo attractant

CollagenCollagen

They are the most abundant proteins They are the most abundant proteins in mammals in mammals

They are secreted by fibroblastThey are secreted by fibroblast At least 13 types have been At least 13 types have been

described described Type 1- 4 are most commonType 1- 4 are most common Rich in glycine and prolineRich in glycine and proline

Collagen contd.Collagen contd.

During fibroblastic phase PDGF,TGF During fibroblastic phase PDGF,TGF & EGF stimulate fibroblast& EGF stimulate fibroblast

Initially type 3 is secreted in higher Initially type 3 is secreted in higher conc: (as in embryo)conc: (as in embryo)

Collagen degradation by collagenase Collagen degradation by collagenase occurs concurrently with collagen occurs concurrently with collagen synthesissynthesis

Matrix metalloproteasesMatrix metalloproteases Comprise the core wound enzymeComprise the core wound enzyme

Brings about wound remodelling by Brings about wound remodelling by matrix degradationmatrix degradation

Produced by fibroblast Produced by fibroblast

Regulated by cytokines Regulated by cytokines

Increased level is seen in chronic woundsIncreased level is seen in chronic wounds

Factors affecting wound Factors affecting wound healinghealing

Local factorsLocal factors1.1. InfectionInfection2.2. Blood supplyBlood supply3.3. Foreign bodyForeign body4.4. Tissue characteristicsTissue characteristics Epithelium heals wellEpithelium heals well Nerve cells, cardiac muscle Nerve cells, cardiac muscle

once once injured,do not heal injured,do not heal

Factors affecting wound Factors affecting wound healinghealing

Systemic factors:Systemic factors: AgeAge NutritionNutrition Haematologic disturbanceHaematologic disturbance DiabetesDiabetes Renal failureRenal failure JaundiceJaundice MalignancyMalignancy

Systemic factorsSystemic factors

SteroidsSteroids Immune deficiencyImmune deficiency Cytotoxic drugsCytotoxic drugs Whole body irradiationWhole body irradiation

Nutrition & wound Nutrition & wound healinghealing

GlucoseGlucose

ATP, source of cellular energy ATP, source of cellular energy

Diabetes impairs wound healingDiabetes impairs wound healing InhibitsInhibits

FibroblastFibroblast

Endothelial cellsEndothelial cells

Leucocyte chaemotaxisLeucocyte chaemotaxis

Components of phospholipid and prostaglandinsComponents of phospholipid and prostaglandins

PhospholipidPhospholipid Cell membrane synthesisCell membrane synthesis

ProstaglandinsProstaglandins Important in inflammationImportant in inflammation

Deficiency of free fatty acids causes impaired wound Deficiency of free fatty acids causes impaired wound healinghealing

FatsFats

ProteinsProteins

Deficiency causesDeficiency causes

Impaired collagen deposition Impaired collagen deposition Decreased wound breaking Decreased wound breaking

strengthstrength Increased wound infection ratesIncreased wound infection rates Decreased angiogenesisDecreased angiogenesis Decreased cellular replicationDecreased cellular replication

Glutamine Glutamine Most abundant amino acid Most abundant amino acid Essential for lymphocyte Essential for lymphocyte

proliferationproliferation Stimulates immune responseStimulates immune response Precursor for synthesis of Precursor for synthesis of

nucleotides in fibroblasts & nucleotides in fibroblasts & macrophages macrophages

Amino acidsAmino acids

ArginineArginine

Enhances collagen deposition Enhances collagen deposition

Enhances wound breaking strengthEnhances wound breaking strength

Substrate for nitric oxide synthesisSubstrate for nitric oxide synthesis

NO important in wound healingNO important in wound healing

VitaminsVitamins Vitamin AVitamin A

Influence inflammatory response in Influence inflammatory response in woundswounds

Increase macrophage influx Increase macrophage influx

Stimulates collagen synthesis, cross Stimulates collagen synthesis, cross linkinglinking

Stimulates epithelialisationStimulates epithelialisation

VitaminsVitamins Vitamin C deficiencyVitamin C deficiency

Impaired collagen synthesis & cross Impaired collagen synthesis & cross linkinglinking

Decreased angiogenesisDecreased angiogenesis

HaemorrhageHaemorrhage

Susceptibility to infectionSusceptibility to infection

VitaminsVitamins

Vitamin EVitamin E

Decreases excess scar formationDecreases excess scar formation

As an antioxidantAs an antioxidant

MicronutrientsMicronutrients

MagnesiumMagnesium Co-factor for protein synthesis Co-factor for protein synthesis Provide structural stability to ATP & Provide structural stability to ATP &

collagen synthesiscollagen synthesis

ZincZinc Important in immune function Important in immune function Deficiency causes wound infectionDeficiency causes wound infection

IronIron For hydroxylation of Proline & For hydroxylation of Proline &

Lysine Lysine

Part of Oxygen transport systemPart of Oxygen transport system

Deficiency Deficiency Impaired collagen productionImpaired collagen production

Diabetes MellitusDiabetes Mellitus

Fibroblast & endothelial cells adversely Fibroblast & endothelial cells adversely affectedaffected

Collagen deposition reducedCollagen deposition reduced

Wound Remodelling reducedWound Remodelling reduced

Chaemotaxis & phagocytosis reducedChaemotaxis & phagocytosis reduced

Renal failure→ adverse effectRenal failure→ adverse effect

Tissue ischemiaTissue ischemia

Tissue oxygen pr < 40mm hgTissue oxygen pr < 40mm hg Delayed wound repairDelayed wound repair

Reduced collagen formationReduced collagen formation

Reduced cross linkingReduced cross linking

Tissue ischemiaTissue ischemia

Tissue OTissue O22 pressure < 30 mm hg pressure < 30 mm hg

Reduced killing of bacteria by Reduced killing of bacteria by phagocytosisphagocytosis

Inhibition of angiogenesisInhibition of angiogenesis

Inhibition of epithelialisationInhibition of epithelialisation

Wound debridementWound debridement

Reduces effects of ischaemia on Reduces effects of ischaemia on wound healingwound healing

Removes tissue laden with bacteriaRemoves tissue laden with bacteria

Types of wound healingTypes of wound healing

PrimaryPrimary

Delayed primayDelayed primay

Secondary intentionSecondary intention

Ideal wound dressing

• Mechanical & bacterial protection

• Moist environment

• Facilitate epithelialisation

• Allow gas & fluid exchange

• Remain non adherent

Ideal wound dressing – Ideal wound dressing – contd.contd.

Non toxic & non allergenicNon toxic & non allergenic Highly absorbable & sterileHighly absorbable & sterile Easy to use Easy to use Suitable forms & sizes should be Suitable forms & sizes should be

availableavailable Aesthetically attractiveAesthetically attractive Cost effectiveCost effective

Occlusive wound dressing

•Non resorbable

•Sterile or non sterile device

•Covers the wound

•Moist environment

•Allow gas & fluid exchange

Advantages of occlusive Advantages of occlusive dressingsdressings

↓ ↓ dehydration and cell deathdehydration and cell death ↑ ↑ angiogenesisangiogenesis Enhanced autolytic debridementEnhanced autolytic debridement ↑ ↑ re – epithelisationre – epithelisation Bacterial barrier and ↓infection Bacterial barrier and ↓infection

ratesrates ↓ ↓ PainPain ↓ ↓ CostsCosts

Non biologic occlusive dressing

• Films & foams

• Hydrocolloids

• Alginates

• Hydrogels

• Silicon gel coats

• Octylcyano acrylate

Biologic Occlusive Dressing

• Allograft

• Xenograft

• Amnion

• Skin substitutes