Tissue Dynamics Ti D i

Chapter 3 Patricia Relue

Tissue replacement rates (Table 3.1) (T bl 3 1)

Bone marrow makes as many cells as comprise it every 2-3 days

Difference between rate and characteristic time

Characteristic time, units of time time Rate or reaction rate, units of time-1 Reaction rate and characteristic time are inversely related

Example: exponential decay. The half-life p p y is the characteristic time for the process. If the rate of decay increases, the half-life decreases. Example: growth rate of cells and the cell doubling time

Short characteristic time, fast rate

Dynamic states of tissue D i t t f ti

Tissue homeostasis

Tissue repair

Normal steady state function of tissue Cell production (bone marrow), transport (kidney, lungs), (kidney lungs) secretion (glands) Healing response due to wound Observed in initial integration of graft tissue Developmental biology and morphogenesis Younger ti Y tissues possess more organogenic i potential Stem cells

Tissue formation (Chapter 4)

Bone marrow and h B d hematopoiesis t i i

Most rapidly replacing tissue, every 2-3 days 400 b ll billion cells/day produced ll /d d d Most cells produced are highly differentiated and short-lived diff i d d h li d T cell, B cell, erythrocyte, neutrophil, monocyte hil (macrophage), eosinophil, basophil, and megakaryocyte (platelet)
5

Villi in the small intestine (Fi 3.1) i t ti (Fig 3 1)

Cell C ll production d ti occurs in the crypt Differentiate as they move up the crypt Mature cells leave the crypt yp Function in the absorption of nutrients for gut g lumen; cell turnover every ~5 days, die g and slough off
6

Skin (Fi Ski (Figure 3.2) 3 2)

Basal layer has Type VII collagen ll 1 in 10-12 basal cells is progenitor cell ll Turnover is a few weeks

Wound h li video W d healing id

http://www.youtube.com/watch?v=zZpMQ_7qiRg

Wound healing in adult skin (Figure 3 3) (Fi 3.3)

Granulation tissue has Agents released by platelets now rapid adhesion Control of bleeding starts withInflammatory cells formed (d f d (dense fibroblasts, fib circulating platelets to dil ti of and ti t the injury cause vasodilation idamageth iblj d d increase blood of bl t site migrate to macrophages, andActivated platelets secrete contents of storageto vessel permeabilityNeutrophils begin developing degranulate and die vasculature) Clotting cascade initiated, fibrinogen granules, spread, recruit more platelets Macrophages arrive Matrix is mainly fibronectin, cleaved by thrombin to form fibrin Thrombusi develops collagen I & III and hyaluronic plug ll III, dh l l from circulation f i l ti Hemorrhaging is contained fibronectin vessel by Macrophages tissue blood holds Fibrin plug + acid constriction secrete compounds Collagen increases the tensile together and forms provisional matrix strength of the wound Hemostasis Thrombosis Matrix recruits inflammatory cells Inflammationto attract endothelial Granulation tissue/ M fib bl t contract, Myofibroblasts t t and l t fibroblasts and d th cellst d later fib bl cells neovascularization t ll and fib bl ll d other fibroblasts, Epidermal cells stimulate proliferation proliferate and pulling wound margins migrate across the Basal layer reforms together wound Epidermis has stratified in epidermal layer

Stages of wound repair St f d i

Hemostasis H t i Thrombosis Granulation G l ti tissue/neovascularization Tissue remodelling

Wound appears healed Matrix is synthesized/degraded Collagen type III replaced by type I Processes determine scar formation
10

Cartilage repair (Fi C til i (Figure 3 4) 3.4)

Placement of reconstituted tissues in vivo induces responses similar to wound healing

11

Engineered wound h li E i d d healing

Square, full thickness wound made in skin S f ll thi k d d i ki Porous ECM template inserted into wound

Composed of collagen I and chondroitin-6p g sulfates Variable pore size Variable degradation rates

Templates were tested for ability to delay wound contracture and promote dermal regeneration Time required for the wound area to decrease by 50% was measured
12

Effect of porous template on wound h li (Fi d healing (Figure 3 5) 3.5)

Optimal range of pore diameter (maximum wound healing delay)

Degradation rate was found optimal when tuned to normal 13 healing rate, td ts

Effect of pore size and degradation on wound healing rate

It i th is thought th t the delay in wound ht that th d l i d healing is related to improved healing correlates to fibroblast migration Wound contracture normally occurs after fibroblasts span the provisional matrix and change to myofibroblasts Small pore sizes (<20 m)

Fibroblasts cannot penetrate the matrix analog Area per volume for cell adhesion is small

Large pore sizes ( 20 m) (>120 )

14

Contraction of cell-laden matrices (Figure 3 6) (Fi 3.6)

Example of in vitro wound healing response Cells apply tension to the ECM Tension results i matrix T i lt in t i contraction Circular matrices contract to a smaller diameter by action of cells on matrix (diameter decreases) MMP inhibitors prevent cell-matrix contraction Ability of cells to remodel a d o a and contract matrix is a used to engineer tissue in vitro
15

Aspects of fetal and adult wound healing h li responses (T bl 3 2) (Table 3.2)

Insight into fetal wound healing can provide stategies for improving 16 adult wound healing and integration of TEMPs into the body

Tissue dynamics as interacting cellular fate processes (Figure 3.7)

Pathology

Means for cells to communicate and coordinate their efforts

17

Questions? Q ti ?

18