Biomaterial-based approaches for vascularization in bone tissue engineering and regenerative medicine

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Abstract/Contents

Abstract
The fields of tissue engineering and regenerative medicine hold great promise to advance the treatment of large-scale bone defects caused by trauma and disease. However, the development of engineered tissues is held back by the challenge of reestablishing functional vascular networks throughout large defect volumes. This dissertation explores two strategies to encourage the reconstruction of large bone defects through the design and synthesis of new biomaterials for use as scaffolds to support and guide new tissue growth. The first approach explored is to incorporate a major blood vessel surrogate within large tissue engineered constructs to surgically establish a supply of blood through the regenerating tissue. Current synthetic vascular grafts used in clinic display undesirable mechanical properties and scarce tissue remodeling. A new family of elastic polyurethanes was developed to better match the complex properties required for vascular compatibility. Gradual degradation of the material in vivo enables scaffolds to be replaced by native tissues. Porous, tough, and compliant vessel grafts were fabricated using a heat cure/porogen extraction molding technique. When implanted in rats, these grafts supported robust vascular tissue redevelopment and sustained blood flow for up to four months. The second approach explores a modification to the induced membrane technique for bone reconstruction. The induced membrane is a vascularized fibrous layer of tissue that forms around poly(methyl methacrylate) bone cement spacers as part of a foreign body reaction. This membrane provides a privileged environment for bone healing in subsequent reconstructive steps, but the mechanism by which the induced membrane promotes regeneration is poorly understood. Two preclinical models are presented here to evaluate the potential of synthetic engineered membranes as alternatives to the traditional biomembrane and to investigate the biological mechanism by which the spacer material induces membrane properties. By providing models to elucidate biomaterial effects on bone healing, we believe that improved bone tissue engineering therapies may be developed

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2020; ©2020
Publication date 2020; 2020
Issuance monographic
Language English

Creators/Contributors

Author Stahl, Alexander Martin
Degree supervisor Yang, Yunzhi Peter
Thesis advisor Yang, Yunzhi Peter
Thesis advisor Cegelski, Lynette
Thesis advisor Heilshorn, Sarah
Degree committee member Cegelski, Lynette
Degree committee member Heilshorn, Sarah
Associated with Stanford University, Department of Chemistry.

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Alexander Stahl
Note Submitted to the Department of Chemistry
Thesis Thesis Ph.D. Stanford University 2020
Location electronic resource

Access conditions

Copyright
© 2020 by Alexander Martin Stahl

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