Ch 9 Wound healing Flashcards
Novel extracellular matrix wound dressing shows
increased epithelialization of full-thickness skin
wounds in dogs
Kierski 2023
surgically created full-thickness wounds
15 purpose-bred Beagles
Subjective wound
assessment scores of wounds treated with ECM did not differ
novel ECM dressing epithelialized more rapidly than wounds treated by a standard protocol
A cellular
fish skin grafts for the management of wounds in dogs and cats: 17 cases (2019–2021)
Mauer 2020
13 dogs and 4 cats with complex wounds
limitation of the present case series was the small sample size and retrospective nature of the study, with various wound management techniques used. As there was no control group, it was difficult to determine the impact that FSGs had on wound healing
o Cell signal types, to self or others
Autocrine- signaling molecules > acts only on that cell or cells of same type
Paracrine- signaling molecules that act on different but local cell types
Juxtacrine – contact-dependent signaling, occurs between cells in contact
Endocrine- cell signals act on cells after traveling via blood
Phases of wound Healing (3)
Inflammation
proliferative
maturation
- Inflammation and debridement
early + late phase
EARLY PHASE
(establishes an immune barrier, provisional scaffold )
Vascular endothelial damage (PG, NA)>vasoconstriction> Coag cascade initiates thrombin formation >fibrin formation >platelet activation
Platelet alpha granules PDGF, TGF-β, VEGF >neutrophil attraction and vasoconstriction
vasodilation leading to heat, redness dt PG, Histamine
Neutrophils
arrive 24-48 hours (TNF-α, IL-1)
Phagocytosis (release ROS, cytokine)
superoxide to kill bacteria
TNF- α- macrophage and fibroblasts
LATE PHASE
Macrophages
48-96 hours
attracted by TGF- β
Release IL-1, IL-6, TNF-α and GF
phagocytosis and release proteases
MMP-1,2,3,9) degrade ECM to facilitate cell movement
Erythema and edema around wound edges
- Proliferation- day 4-12
5 stages
- Angiogenesis - occurs in response to VEGF and bFGF (keritinicytes), can be visible 4 days post surgery
- Fibroblast migration – migrate to wound and proliferate in response to PDGF, TGF-β. produce definitive ECM - collagen type III
- Collagen Synthesis: Type III initially predominates, * TGF- β increases type I, decreases MMPs, transform fibroblasts to myofibroblasts
Granulation bed: capillary bed, fibroblasts, macrophages + ECM
o Appearance is sign of healthy tissue, risk of infection reduced - Contraction: * Myofibroblasts orient linearly along line of tension to cause wound contraction
- Epithelization – in response to epidermal growth factor, TGF-a (platelets + macrophages) FGF-2 from keratinocytes.
* keratinocytes from the basal lamina mobilize across wound
* Migration continues until contact inhibition
dermis contains 80% type I collagen and 20% type III
- Remodeling and Maturation
3mo post wounding max strength regained is 80%
o Capillaries regress and collagen reorganizes along lines of tension
o Granulation tissue 30% type III collagen, remodeled so final scar only 10% type III
o Collagen synthesis usually done in 4-6 wks, maturation can continue 12-18 months
GI Healing
4 layers, lag phase
- Mucosa
3 layers: epithelium, lamina propria muscularis mucosa - Submucosa – provide tensile strength
o Type I (68%), II (20%), V (12%) collagen - muscularis propria
smooth muscle and collagen (circular layer and an outer longitudinal) - serosa
epithelial seal within 3 days with direct contact
macrophages are a key source of growth factors
Collagen breakdown secondary to collagenase activity within the wound occurs during this “lag phase” in the first few days of the healing process and results in net loss of strength of the anastomotic closure
Sepsis is associated with a generalized upsurge in collagenase
GIT vs skin healing
5 differences
bacteria (aerobic and anaerobic)
collagen type (I, III, V)
collagenase activity days 0-3
vascular perfusion down regulated in shock
wound shear increased due to perstalisis
Fascial Healing
prolonged inflammatory phase of wound healing
fascial fibroblasts have also been shown to have a higher rate of collagen synthesis on day 7 > fascia requires 14 weeks to regain 60% strength
(1) failure due to early, high mechanical forces;
(2) healing optimized by continuous, nonabsorbable or slowly absorbable, inert sutures;
(3) sutures placed 3 mm from the wound edge, outside the active zone of inflammation.
- Urinary Bladder Healing
bladder reepithelializes in 2 to 4 days
GF involed: EGF and TGF-α
o Collagen synthesis peak > 5 days
regains 100% strength within 21 days,
collagen synthesis does not return to normal until 70 days post injury
- Bone Healing
Ossification?
Inflamm and GF?
BMP
intramembranous and endochondral ossification
Endochondral predominant – cartilage matrix produced, becomes mineralized, then resorbed as bone is produced
o inflammatory mediated through proinflammatory cytokines (TNF-α, PDGF, TGF-β, VEGF, and FGF)
o [BMPs] modulate and mediate the healing of bone primarily through the stimulation of undifferentiated mesenchymal cells
- SPECIES DIFFERENCES IN HEALING
Primary vs secondary healing
SQ
Epithelialissatt
o 1st intention healing
> cat breaking strength only half that of the dogs at 7d, equal by 14d
o 2nd intention healing
> granulation tissue faster and central in dogs (4.5d) vs cats (6.3d and peripheral)
o Mean time to cover wound with g.t.
Dogs: 7.5 days
Cats: 19 days
Also noted removal of subcutaneous tissue slowed g.t. formation and wound contraction
epithelialisation by 14d:13% in cat vs
Dogs 44%
IMPEDIMENTS TO WOUND HEALING
* Local Factors (4)
o Wound Perfusion
> systemic: shock, hypotension, hypovolemia, pain, DM
> intercapillary distances are large
> Partial pressure of oxygen is most important (more than amount of oxygen bound to Hgb entering the wound bed)
> Core hypothermia
o Tissue Viability and Fluid accum.
> necrotic tissue, excessive bacterial burden, foreign material
> Fluid mechanically disrupts wound, can cause ischemia if pressure from fluid exceeds capillary perfusion pressure , dead space + infection
> Seromas: dt inflammation and dead (drain)
o Wound Infection
> inflammatory phase – Platelets depleted, WBC impaired. cytotoxic enzymes and ROS increase tissue damage
> proliferative phase – fibroplasia, angiogenesis, and epithelization all impacted. Bacterial proteases and inflammation> breakdown granulation tissue, overall decreased wound strength
> Role of perfusion critical in delivery of antibiotics to wound
o Mechanical Factors
> Primary closure: smaller wound volume, stabilizes distractive forces, promotes healing through synthesis of new matrix (2nd intension has prolong healing time)
VAC counteracts many negative mechanical factors
Systemic Factors (3)
- Impaired Immune Function
> Immunosuppression
> Primary disease: FIV, hyperA, DM
> seondary: CCS, chemo
no vet literature directly linking DM to delayed wound healing
> Endocrinopathies increase risk of wound infection (Nicholson et al.)
o Transfusion related - Cancer
o Chemo: cytotoxic, antiproliferative
o Radiation affects local vasculature
o Can cause “fibrotic microangiopathy”
> delay radiation until acute phase of healing is done
o Cancer cachexia - Age
o Some animal model studies have shown differences in healing in older vs younger animals, the clinical impact might be more dependent on concurrent disease processes
