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Poly(diol citrate)-Hydroxyapatite Nanocomposites for Bone and Ligament Tissue Engineering

Posted on:2012-10-26Degree:Ph.DType:Thesis
University:Northwestern UniversityCandidate:Chung, Eun JiFull Text:PDF
GTID:2464390011458097Subject:Biology
Abstract/Summary:
Over 500,000 bone grafting procedures and 250,000 anterior cruciate ligament (ACL) reconstructions are performed in the US annually. Current treatments rely on obtaining donor tissues and pose disadvantages including donor site morbidity, supply limitations, and the risk of disease transfer. In order to circumvent these shortcomings, synthetic solutions are investigated in the field of tissue engineering.;Incorporating hydroxyapatite (HA) to biodegradable polymers provides structural similarity to bone and the utility of poly(1,8-octanediol-co-citrate)-HA (POC-HA) microcomposites for bone applications was previously confirmed. Herein, novel POC-HA nanocomposites are fabricated and the mechanical properties, hydrophilicity, degradation, and osteogenicity using human mesenchymal stem cells (hMSC) are assessed. The material properties and bioactivity of POC-HA nanocomposites are favorable for bone applications and the extent of these characteristics are dependent on the HA content.;To clarify the effect of HA size, the material properties and in vivo response of POC-HA nanocomposites vs. microcomposites are compared. The mechanical properties and bone regeneration at the implant-tissue interface of POC-HA nanocomposites are superior to POC-HA microcomposites at 6 weeks. Furthermore, in vivo studies were extended to 26 weeks and the safety of POC-HA nanocomposites and its equivalence to FDA-approved polymers are confirmed.;In addition, novel, porous POC-HA nanocomposite scaffolds are fabricated through low pressure foaming (LPF). The effect of HA content and pre-polymer viscosity on porosity, mechanical properties, and biocompatibility using hMSC is evaluated. POC-HA scaffolds mimic the porous structure of trabecular bone, are mechanically superior to salt-leached scaffolds in aqueous conditions, and support hMSC attachment and alkaline phosphatase activity.;Furthermore, porous POC-HA scaffolds are wrapped around a braided poly(L-lactide) core to construct a tri-component graft for ACL repair, and the material properties and in vivo response are assessed. The mechanical properties, degradation, and porosity are suitable for ACL repair, and reconstructed animals displayed good functionality and tissue regeneration at 6 weeks. Although preliminary, this is the first study to report a graft with bony ends for ACL repair. Collectively, the data presented in this thesis confirm the versatility of POC-HA nanocomposites and provide a basis for their utilization in orthopaedic applications.
Keywords/Search Tags:POC-HA nanocomposites, ACL, Mechanical properties, Tissue, Poly
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