Amphiphilic Degradable Polymer/Hydroxyapatite Composites as Smart Bone Tissue Engineering Scaffolds: A Dissertation
Authors
Kutikov, Artem B.Faculty Advisor
Jie Song, PhDAcademic Program
Cell BiologyUMass Chan Affiliations
Orthopedics and Physical RehabilitationDocument Type
Doctoral DissertationPublication Date
2014-11-24Keywords
Dissertations, UMMSAutografts
Biocompatible Materials
Bone Morphogenetic Protein 2
Bone and Bones
Bone Transplantation
Tissue Scaffolds
Tissue Engineering
Polymers
Autografts
Biocompatible Materials
Bone Morphogenetic Protein 2
Bone and Bones
Bone Transplantation
Tissue Scaffolds
Tissue Engineering
Polymers
Biomaterials
Cell Biology
Molecular, Cellular, and Tissue Engineering
Musculoskeletal System
Orthopedics
Metadata
Show full item recordAbstract
Over 600,000 bone-grafting operations are performed each year in the United States. The majority of the bone used for these surgeries comes from autografts that are limited in quantity or allografts with high failure rates. Current synthetic bone grafting materials have poor mechanical properties, handling characteristics, and bioactivity. The goal of this dissertation was to develop a clinically translatable bone tissue engineering scaffold with improved handling characteristics, bioactivity, and smart delivery modalities. We hypothesized that this could be achieved through the rational selection of Food and Drug Administration (FDA) approved materials that blend favorably with hydroxyapatite (HA), the principle mineral component in bone. This dissertation describes the development of smart bone tissue engineering scaffolds composed of the biodegradable amphiphilic polymer poly(D,L-lactic acid-co-ethylene glycol-co- D,L-lactic acid) (PELA) and HA. Electrospun nanofibrous HA-PELA scaffolds exhibited improved handling characteristics and bioactivity over conventional HApoly( D,L-lactic acid) composites. Electrospun HA-PELA was hydrophilic, elastic, stiffened upon hydration, and supported the attachment and osteogenic differentiation of rat bone marrow stromal cells (MSCs). These in vitro properties translated into robust bone formation in vivo using a critical-size femoral defect model in rats. Spiral-wrapped HA-PELA scaffolds, loaded with MSCs or a lowdose of recombinant human bone morphogenetic protein-2, templated bone formation along the defect. As an alternate approach, PELA and HA-PELA were viii rapid prototyped into three-dimensional (3-D) macroporous scaffolds using a consumer-grade 3-D printer. These 3-D scaffolds have differential cell adhesion characteristics, swell and stiffen upon hydration, and exhibit hydration-induced self-fixation in a simulated confined defect. HA-PELA also exhibits thermal shape memory behavior, enabling the minimally invasive delivery and rapid (>3 sec) shape recovery of 3-D scaffolds at physiologically safe temperatures (~ 50ºC). Overall, this dissertation demonstrates how the rational selection of FDA approved materials with synergistic interactions results in smart biomaterials with high potential for clinical translation.DOI
10.13028/M2X889Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32118Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/M2X889
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