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Physiology of wound healing

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Physiology of wound healing Wound healing is: Complicated process that involves at least 4 distinct cell types Commonly referred to as occurring in PHASES – PowerPoint PPT presentation

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Title: Physiology of wound healing


1
Physiology of wound healing
  • Wound healing is
  • Complicated process that involves at least 4
    distinct cell types
  • Commonly referred to as occurring in PHASES
  • Affected by several factors

2
Phases of wound healing process (WHP)
Maturation
Proliferation
Inflammation
Haemostasis
Where does a chronic wound get stuck?
3
Platelet Activity
WOUND
Tissue factor
Exposed collagen
Extrinsic pathwayVII
Intrinsic pathwayXII
Messengers for Aggregation coagulation
Intrinsic pathway intermediates IX, VII
Platelet
Growth factors(PDGF)
Coagulation pathway intermediates V, X
Other enzymes (proteases)
Fibrinogen
Prothrombin thrombin
Xlila
Cross-linked fibrin clot (structural support for
wound healing)
FIBRIN
4
Role of keratinocytes in wound healing
Keratinocyte
Migration/ Profileration
Protease release
ECM production
Angiogenesis
  • Dissolves
  • Nonviable tissue
  • Fibrin barrier

Growth factor/ Cytokine production
  • Epibloy
  • Integrins
  • Chemoattractants
  • VEGF
  • KGF (FGF-7)
  • Matrix formation
  • Basement membrane formation
  • VEGF
  • TGF-a
  • PDGF
  • PD-ECGF

5
Selected growth factors important to wound healing
  • EGF (epidermal growth factor). Stimulates wound
    re-epithelialization and stimulates blood vessels
    and fibroblasts.
  • FGF (fibroblast growth factor). Stimulates new
    blood vessel and collagen formation.
  • PDGF (platelet derived growth factor).
    Attracts/stimulates smooth muscle cells,
    fibroblasts, and other cells. Important in ECM
    formation.
  • TGF-ß (transforming growth factor-beta). Slows
    buildup of epithelial cells, suppresses
    immunoglobulin secretion and is helpful in ECM
    formation.
  • TNF-a (tumor necrosis factor-alpha). Activates
    neutrophils, causes fibroblasts to multiply,
    causes bone/cartilage resorption.
  • IL-1 (interleukin-1). Attractant for epithelial
    cells, neutrophils, mono and lymphocytes also
    stimulates collagen synthesis.

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7
Chronic wounds characteristics
  • Increased inflammatory cytokines
  • Altered fibroblast phenotype
  • Abnormalities growth factors
  • Increased proteases
  • Altered keratinocyte function
  • Senescent cells (increased number)

8
Wound bed preparation
  • Debridement
  • Bacterial balance
  • Dressing therapies
  • (f.i. silver dressings prevent of infections,
    help reduce healing time)

9
Local wound care
debridement
moisture balance
Foams Calcium alginates Hydrogels Hydrocolloids Ad
hesive films Negative pressure therapy
Surgical Autolytic Enzymatic Biological
10
Tissue engineering
  • Biology, medicine and technology are today
    closely interleaved with each other

11
  • Tissue engineering combining cells and
    biomaterials into functional tissues
  • Cells are seeded onto a biomaterial scaffold
    to be integrated into a specific tissue

12
Tissue engineering
  • Advances
  • Biological wound dressings
  • Material scaffolds and cell material interactions
  • The use of stem cells for tissue engineering
  • Combination of stem cells and material scaffolds
    into tissue engineered replacements of tissues
    and organs

13
Tissue engineering implants
  • Synthetic polymeric biomaterials
  • Nonbiodegradable
  • Is required to provide and maintain optimal
    cellular function -gt e.g. alginate, liposome,
  • Biodegradable
  • To restore the histological structure and
    replace the cellular function of recipients -gt
    e.g. poly L-lactic acid, poly glycolic acid,

14
Wound healing promoting anti-adhesive matrix
  • The collagen grafting is also applied to
    produce a healing / promoting antiadhesive
    membrane
  • Particularly necessary in peritoneal surgery to
    prevent postoperative adhesion
  • To produce skin wound dressing membranes

15
Methods of tissue bioengineering
  • Skin replacement
  • Cultured epidermal graft
  • Cultured human autologous and allogeneic
    keratinocytes
  • Semi synthetic materials (composed of human
    neonatal dermal fibroblasts cultured onto a
    bioabsorbable mesh)

16
Methods of tissue bioengineering
  • Active dressings (f.i. with maggots excret,
    with honey)
  • Photobiomodulation (modulate cellular activity in
    red to near infrared light)
  • Hyperbaric oxygen therapy as therapeutic benefit
    in WT
  • Growth factors (from blood)

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18
Allogeneic cultivated human skin keratinocytes
  • Make rapid healing of the ulcers particularly
    those that are difficult to heal
  • No clinical or laboratory evidence of rejection
  • No evidence of preexisting cytotoxic antibodies
    specific fort the HLA class I antigens expressed
    on HSE cells
  • A fibrin-based skin substitute produced in the
    defined keratinocyte medium could be safely used
    to threat a number of skin defect

19
Preparation of autologous fibrin-based skin
substitutes
20
Methods of tissue bioengineering
  • Autologous platelet rich plasma product (platelet
    gel)
  • Allogeneic platelet gel
  • The effect is attributed to the growth factors

21
Impaired healing
Delayed unionPseudoarthrosis - nonunion (bone
defect)
Fracture
Impaired healing
? Method of treatment?
Infection
22
  • Large bone defect
  • Lack of osteogenic progenitor cells
  • Diabetes, glucocorticoid treatment, chemotherapy,
    ...

23
Accepted methods of treatment
  • Autologous bone transplants
  • Cancellous bone graft (contains all necessary
    characteristics of bone substitutes)
  • Corticocancellous graft (possibly vascularized?
    limited amount)
  • Homologous (allogeneic) graft
  • Bone banks, treated (no rejection), contains
    only osteoconductive properties
  • Ilizarow intercallary bone transport (traction
    method)

24
Properties of bone grafts
  • Osteogenesis (bone marrow, cancellous bone)
  • Osteoinduction
  • Demineralized bone matrix
  • Growth factors (platelet rich plasma, bone
    morphogenic proteins BMPs)
  • Osteoconduction
  • Ceramics
  • Collagen

25
Alternatives
  • Bone substitute (biomaterials for scaffold)
  • Demineralized bone matrix
  • Biocompatible ceramics
  • Synthetic Calcium phosphate
  • Mineral bone
  • Collagen
  • Composite grafts
  • Osteoinductive collagen

26
Alternatives
  • Role of GROWTH FACTORS
  • Role of STEM CELLS

27
Collagen based matrices in tissue engineering
  • Skin equivalent
  • Cartilage repair
  • Bone repair
  • Matrices are also prepared from synthetic
    polymers

28
Fracture healing promoting molecules
  • Growth and different factors
  • The transforming growth factor-ß (TGF-ß)
    superfamily
  • Bone morphogenetic proteins(osteoprogenitors,
    mesenchymal cells, osteoblasts and chondrocytes
    within the extracellular matrix produce
    BMPs.)BMP-2, BMP-4BMP-5, BMP-6, BMP-7GDF-5
    (BMP-14), GDF-6 (BMP-13), GDF-7 (BMP-12)BMP-3
    (Osteogenin), GDF-10 (BMP-3b)
  • Platelet-derived growth factor (PDGF)
  • Fibroblast growth factor (FGFs)
  • Insulin-like growth factor (IGFs)

29
  • Platelet rich plasma (contains high
    concentrations of growth factors) especially
    TGF-B and PDGF
  • Autologous
  • Allogeneic

PLATELETS
MONOCITE
NEUTROPHILS
PDGF TGF-ß
FIBROBLAST
SMOOTH MUSCLE
MACROPHAGE
ENDOTHELIUM
OSTEOBLASTS
PDGF TGF-ß
30
  • Mesenchymal stem cell the promise for treating
    skeletal disorders
  • Adult stem cell are being isolated from various
    tissues

31
Adult stem cells
  • Bone marrow contains
  • Hematopoietic stem cells (HSCs)
  • All types of blood cells
  • Bone marrow mesenchymal stem cells (MSCs)
  • Generating bone, cartilage, fat, fibrous
    connective tissue

32
Bone tissue formation
  • Osteogenic progenitor cells
  • Locations
  • Periost
  • Peritrabecular soft tissue
  • Cancellous bone and bone marrow (in BM aspirate
    up to 40x less stem cells then in cancellous bone)

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35
Our method of tissue engineering
  • Combined graft
  • Autologous cancellous bone withstem cells
  • Allogeneic platelet gel(source of GFs)

36
  • manually grounded autologous cancellous bone
    with stem cells
  • corresponding amount of allogeneic platelet
    concentrate (app. 1,4x109 platelets per 1 ml)
  • AND
  • Added 0,06 ml human thrombin in 40 mM CaCl2
    for the activation of platelets
  • in 1
    minute
  • the resulting gelled graft can be shaped
    according to the bone defect and implanted

Mixed
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39
Our graft
  • Autologous cancellous bone with stem cells and
    allogeneic platelet gel

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41
Conclusions
  • The use of autologous cancellous bone with
    stem cells and allogeneic platelet gel is safety
    and effective method for the treatment of
    nonunion of long bones

42
Future
Gene arrays for
gene discovery
43
FUTURE
Cell and tissue engineering Detection of
numerous signal pathways activated during
physiological processes Self (re)restoration and
differentiation off mammalian embryonic, fetal
and stem cells of adult tissues
44
  • Thank you for attention !
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