Engineering scaffold and soluble cues for cell-instruction

tissue engineering;collagen scaffold;mechanical properties

Liang, Youyun

关键词: tissue engineering;    collagen scaffold;    mechanical properties;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/45617/Youyun_Liang.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

The ultimate aim of this work is to design and engineer an integrated tissue engineering approach that combines microenvironmental scaffold cues with soluble factor cues so as to enhance cell-instruction and tissue regeneration.In order for this aim to be accomplished, we started off by separately examining the control of microenvironmental cues and the regulation of soluble factor cues both in vitro and in vivo.In the earlier parts of the research, we modified the microenvironmental scaffold cues of collagen-based scaffolds through various approaches.These approaches included (i) covalent cross-linking of collagen scaffolds to increase their bulk stiffness (chapter 4), (ii) enzymatic degradation of covalently cross-linked collagen scaffolds to decrease their bulk stiffness (chapter 5), and (iii) regulation of collagen fiber structure and rigidity through control of the thermodynamic driving force for collagen self-assembly (chapter 6).Through the various modifications, we were able to generate a range of stiffness in the physiologically relevant range and further regulate the malignancy of hepatocellular carcinoma cells and fibroblasts with these cell-instructive scaffolds.In the later part of this research, we fabricated stiff and metastable poly(ethylene glycol diacrylate)-polyethylenimine hydrogels for the release of cytokines in vivo (chapter 7).The high stiffness of the material, attained from the highly branched architecture of polyethylenimine, allowed the hydrogel to release encapsulated substances independent of local tissue pressures.The decoupled control of stiffness and degradation rate was also achieved by tuning the relative numbers of acrylate and protonated amine groups in the fabricated hydrogels.Following synthesis, the hydrogels were extensively characterized in terms of their mechanical properties, degradation, cytotoxicity, in vitro and in vivo drug release.This hydrogel system was also successfully used as an injectable depot for the controlled release of granulocyte colony stimulating factor in porcine models.Although the hydrogel system was only tested with bovine serum albumin and granulocyte colony stimulating factor, we expect this customizable and user-friendly platform to be readily applied to other cytokines.The separate investigations of microenvironmental scaffold cues and soluble factors cues covered in this thesis would provide an important stepping stone for the subsequent combination of these cues in integrated tissue regeneration and cell-instructive applications.As this research only serves as groundwork in the proposed integrated strategy, new issues and challenges are expected to arise.This area will be examined by other members of the laboratories.