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Chondroitin Sulfate Conjugated Nanofiber Shish Kebabs as Biomimetic Bone Templates

Wednesday, January 22, 2020

12:00 PM-2:00 PM

BIOMED PhD Thesis Defense

Chondroitin Sulfate Conjugated Nanofiber Shish Kebabs as Biomimetic Bone Templates

Tony Yu, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Michele Marcolongo, PhD
Department Head and Professor
Department of Materials Science and Engineering
Drexel University

Christopher Li, PhD
Department of Materials Science and Engineering
Drexel University

Bone defects affect over 2.2 million people worldwide through diseases, injuries, aging, or the combination of these. The gold standards for bone defects are autografts harvested generally from the iliac crest or the hip bone of the patient. The use of autografts is limited and require additional surgery, which increases the risk of infection and donor site morbidity. Although there is no immune or compatibility issue, some autografts still fail due to non-union of bone and related complications. There is a medical need to synthesize polymeric bone grafts that can perform similarly if not better than bone autografts. To this end, we have previously fabricated a polycaprolactone (PCL) nanofiber shish kebab (NFSK) template as synthetic bone scaffolds via polymer crystallization of a block copolymer of PCL-b-PAA. The novelty of this work is the ability to control the mineral crystal orientation and spatial location on the nanofiber, which mimics the molecular structure of bone or mineralized collagen fibrils.

The objective of this thesis is two-fold: 1) to investigate the cell to biomaterial surface interaction provided by the unique NFSK surface features and 2) to use the NFSK platform to design biomimetic bone templates. The advantage of using NFSK templates is ease of modifying the template surface with different functional groups and biomimetic nature of NSFK-templated mineralization. As a result, the surface roughness and chemistry can be manipulated and designed towards an osteogenic microenvironment. For these reasons, it was hypothesized that the NFSK templates will promote cell differentiation and marker expression of mineralization of MC3T3 E1 pre-osteoblast cells. In the first part of the dissertation, NFSK templates were used to investigate the topological effect, e.g. fiber alignment and kebab size, on pre-osteoblast cell proliferation and ALP activity, which the latter is an important enzyme related to bone mineralization and osteogenesis. Aligned nanofiber with larger kebab size increased both ALP activity and cell proliferation because of the surface roughness of NFSK. NFSK templates were then mineralized in simulated body fluid to mimic mineralized collagen fibrils, which was showed to increase ALP and cell proliferation as well. Interestingly, the kebab period did not influence proliferation or ALP activity when mineralized indicating that surface chemistry played a more dominant role than surface roughness.

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