麻省理工大学：《生物材料——组织交互作用》教学讲义（英文版）C Synthesis of biologically active scaffolds

C Synthesis of biologically active scaffolds(regeneration templates 1. History of biologically active scaffolds (regeneration templates) 2. Physical chemistry of collagen: Melting of collagen quaternary structure( thromboresistance). Melting of collagen tertiary structure( gelatinization) 3. Synthesis of EcM analogs: lonic complexation collagen/GAG, formation of pore structure, crosslinking 4. Biological activity of ECM analogs depends critically on structure

C. Synthesis of biologically active scaffolds (regeneration templates) 1. History of biologically active scaffolds (regeneration templates). 2. Physical chemistry of collagen: Melting of collagen quaternary structure (thromboresistance). Melting of collagen tertiary structure (gelatinization). 3. Synthesis of ECM analogs: Ionic complexation collagen/GAG, formation of pore structure, crosslinking. 4. Biological activity of ECM analogs depends critically on structure

1. History of biologically active scaffolds(regeneration templates) 1974-75 Synthesis and characterization of the first biologically active scaffolds Scaffolds defined as very highly porous polymeric constructs that are commonly used, either unseeded or seeded with cells, to synthesize tissues and organs in vitro or in vivo (Yannas et al., 1975a, b, c; 1979; 1980a, b, c) 1979-80 First clinical use of a biologically active scaffold to regenerate the dermis(treatment of massively burned children)(Burke et aL., 1981)

1. History of biologically active scaffolds (regeneration templates). • 1974-75 Synthesis and characterization of the first biologically active scaffolds. Scaffolds defined as very highly porous polymeric constructs that are commonly used, either unseeded or seeded with cells, to synthesize tissues and organs in vitro or in vivo (Yannas et al., 1975a,b,c; 1979; 1980a,b,c). • 1979-80 First clinical use of a biologically active scaffold to regenerate the dermis (treatment of massively burned children) (Burke et al., 1981)

1. History of biologically active scaffolds(regeneration templates) (continued) 1981-82 Implantation(grafting of a cell-seeded scaffold. Keratinocyte-seeded template regenerates simultaneously dermis and epidermis in animals (Yannas et aL, 1982) 1985 Regeneration of peripheral nerves across unprecedented distances in animals using a biologically active scaffold (Yannas et al, 1985) 1989 Identification of structural features that account for template regenerative activity(yannas et al, 1989) 1996 FDa approves first scaffold (ntegra for treatment of burned patients and, later, for plastic and reconstructive surgery of skin(2001)

1. History of biologically active scaffolds (regeneration templates). (continued) • 1981-82 Implantation (grafting) of a cell-seeded scaffold. Keratinocyte-seeded template regenerates simultaneously dermis and epidermis in animals (Yannas et al., 1982). • 1985 Regeneration of peripheral nerves across unprecedented distances in animals using a biologically active scaffold (Yannas et al., 1985). • 1989 Identification of structural features that account for template regenerative activity (Yannas et al., 1989). • 1996 FDA approves first scaffold (Integra) for treatment of burned patients and, later, for plastic and reconstructive surgery of skin (2001)

Analogs of extracellular matrix GAGs CS KS PG Collagen fiber

Analogs of extracellular matrix

2. Physical chemistry of collagen Melting of collagen tertiary structure acceleration of biodegradation rate. -- Melting of collagen quaternary structure: thromboresistance

2. Physical chemistry of collagen: --- Melting of collagen tertiary structure: acceleration of biodegradation rate. --- Melting of collagen quaternary structure: thromboresistance

COLLAGEN STRUCTURE Images removed due to copyright considerations

COLLAGEN STRUCTURE II mmages ages r reemmoovveed due t d due too c copy opyright right c cons onsiderat iderations ions

Primary Image removed due to copyright considerations structure (amino acid sequence) Type I collagen

Primary structure (amino acid sequence) of Type I collagen Image removed due to copyright considerations. Image removed due to copyright considerations

Mechanical (viscoelastic) behavior of colagen and gelatin. Proteins were Progressively diluted with glycerol to elicit the entire spectrum Image removed due to copyright considerations of their viscoelastic behavior Gelatin shows a rubberlike state Collagen does not

Mechanical (viscoelastic) behavior of colagen and gelatin. Proteins were Progressively diluted with glycerol to elicit the entire spectrum of their viscoelastic behavior. Gelatin shows a rubberlike state. Collagen does not. Image removed due to copyright considerations. Image removed due to copyright considerations

Degradation of collagen fibers by collagenase Image removed due to copyright considerations Degradation of collagen molecule by collagenase to gelatin Gelatin itself degrades much faster than collagen Image removed due to copyright considerations

Degradation of collagen fibers by collagenase Image removed due to copyright considerations. Image removed due to copyright considerations. Degradation of collagen molecule by collagenase to gelatin. Gelatin itself degrades much faster than collagen. Image removed due to copyright considerations. Image removed due to copyright considerations

Melting of quaternary structure of collagen fibers occurs below pH 4.5. Melting confers thromboresistance to the scaffold, platelets Do not aggregate unless Image removed due to copyright considerations the quaternary structure Is intact. Blocking of platelet aggregation leads to downregulation of the inflammatory response at the site of grafting or implantation

Melting of quaternary structure of collagen fibers occurs below pH 4.5. Melting confers thromboresistance to the scaffold. Platelets Do not aggregate unless the quaternary structure Is intact. Blocking of platelet aggregation leads to downregulation of the inflammatory response at the site of grafting or implantation. Image removed due to copyright considerations. Image removed due to copyright considerations