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ECM Biologic Scaffold (Scaffolds (Material (Natural (ECM (Role (Repair of…

- - - - ECM
        
        Process
        
        Preparation
        
        Harvested & Used
        
        ECM Scaffolds seeded with site specific cells (Autologous Cells)
        from receipient
        
        Tissue Repair
        
        Decellularization
        
        Xenogeneic & Allogenic cellular antigens are treated as foreign by host
        
        Trigger inflammatory response
        
        Tissue Rejection
        
        Role
        
        Repair of musclotendinous structures
        
        Lower urinary tract reconstruction
        
        Esophageal Replacement
        
        Skin Chronic Wound Healing
        
        Upper-airway Reconstruction
        
        Manufacture
        
        Same properties as native tissues
        
        Components
        
        Collagen (1st)
        
        Most abundant protein within mammalian ECM
        
        20 types
        
        Unique biologic function
        
        Mechanical & Physical Properties
        
        Type 1
        
        Major structural protein present in tissues
        
        Found in tendinous & ligamentous structures
        
        Provides strength to accommodate uniaxial & multi axial mechanical loading of tissues
        
        Bovine
        
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        Type 4
        
        Basement membrane of most vascular structures
        
        Ligand Affinity for endothelial cells
        
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        Type 3
        
        Within submucosal tissue of organs
        
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        Type 6
        
        Connect btwn GAG & larger structural proteins like Type 1
        
        Provide Gel-Like Consistency
        
        Type 7
        
        Basement membrane of epidermis
        
        Function
        
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        Result of gene expression patterns
        
        Fiber Architecture
        
        Affects
        
        Biomechanical Behaviour of Scaffold
        
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        Mechanical Loading Effects on Scaffold
        
        Remodelling Process
        
        Fibronectin (2nd)
        
        Applications
        
        Substrate for in vitro cell culture
        
        Coating for synthetic scaffold materials
        
        Promote host biocompatibility
        
        Normal Biologic Development
        
        Properties
        
        Cell-friendly characterisitcs
        
        Rich in RGD subunit
        
        Found
        
        Early stage of developing embryos
        
        Laminin
        
        Complex adhesion protein within basement membrane
        
        Applications
        
        Early Embryonic Development
        
        Purpose
        
        Formation & Maintenance of vascular structures
        
        Most impt in cell and tissue differentiation
        
        Tissue Development
        
        Cell Population Self Assembly
        
        GAG
        
        Purpose
        
        Bind GF & Cytokines
        
        Promote Water Retention
        
        Improve gel properties of ECM
        
        Examples
        
        Heparin
        
        HA
        
        Applications
        
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        Purpose
        
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        Chondroitin Sulfates
        
        GF
        
        Purpose
        
        Act as potent modulators of cell behavior
        
        Types
        
        VEGF
        
        Angiogenesis
        
        bFGF
        
        Stromal-Derived GF (SDGF)
        
        EGF
        
        TGF-beta
        
        Keratinocyte GF (KGF)
        
        Hepatocyte GF (HGF)
        
        PDGF
        
        Granulation Tissue Deposition
        
        Bone Morphogenetic Protein (BMP)
        
        Bone Deposition
        
        Exist in multiple isoforms
        
        Problem
        
        Determine Optimal Dose
        
        Delivery Methods
        
        Sustain release at desired site
        
        Lack of Control
        
        Host Response
        
        Different
        
        VEGF
        
        Induce Angiogenesis
        
        BMP
        
        Induce Bone Formation
        
        Factors
        
        Amount
        
        Duration
        
        Appropriateness
        
        Hard to control
        
        Proteins
        
        Provides mechanical strength
        
        Allows proper function of tissue
        
        Conduit of info exchange btwn cells and ECM
        
        Dynamic Reciprocity State
        
        Change with enviro factors
        
        Hypoxia
        
        Mechanical Loading
        
        Purpose
        
        Provides Structural Support
        
        Provides favourable enviro for constructive remodelling of tissues & organs
  - - - Attachment
      - Migration
      - Proliferation
      - Differentiation
      - 3D Spatial Organization of cell population
  - - - MIcroenviro of each tissue
        
        Factors
        
        Blood Supply
        
        pH
        
        O2
        
        CO2
        
        Mechanical Stressors
        
        Host: Scaffold Interface
        
        Determine scaffold fate
        
        Decide Remodelling Type
        
        Constructive
        
        Requirement
        
        Varies
        
        Intended Application
        
        Preparation Mode
        
        Destructive
        
        Scarring
  - - - Strength
      - Mechanical Properties
- - - - Collagen
        
        Strength Source
        
        Cell Attachment & Differentiation
      - Proteoglycans
        
        Matrix resiliency Source
        
        GAG
        
        Disaccharide backbones
        
        Major Classes
        
        HA
        
        Chondroitin Sulfate
        
        Heparin
        
        Keratan Sulfate
      - Cell Interactive Glycoproteins
        
        Create tissue cohesiveness through cell adhesion capabilities
        
        FIbronectins
      - Elastic Fibers
        
        Flexbility
  - - - Mechanical
      - Enzymatic
      - Physical
    - - Complete decellulariaztion of source tissue
        
        Remove all cellular material
        
        Maintain composition, mech properties & biologic activity
        
        Physical Treatment Methods
        
        Sonication
        
        Massage
        
        Freezing
        
        Thawing
        
        Problem
        
        Disrupt cell membranes
        
        Release cell contents
    - - Xenogeneic
      - Allogenic
  - - - Only with degradation products
        
        Degradation needed for release of biologically active peptides
      - Resistant to bacteria infections