It is estimated that one seventh of the US population suffer from some forms of musculoskeletal impairment. The social and economic implications of the effective treatment of these conditions are enormous. The goal of this project is to design osteoconductive and osteoinductive synthetic bone grafts possessing desirable mechanical strength and biochemical microenvironment for the reconstruction of skeletal defects with compromised natural healing capacities. The grafts are designed to provide instant mechanical protection and structural stabilization to the site of bony defects, and locally release exogenous growth factors and cytokines to promote bone graft healing. Specifically, we propose to incorporate an exogenous supply of BMP-2, RANKL and VEGF to the synthetic bone graft to induce proper host cell responses to elicit the coordinated remodeling and osteointegration of the graft with vascular ingrowth. Using ring opening polymerization and reverse addition fragmentation transfer polymerization in combination with high-fidelity bioconjugation chemistries, polymeric biodegradation domains, growth factor retention domains, bone mineral (hydroxyapatite) nucleation domains and cell adhesion domains are sequentially grafted around Si-based nanoparticle cores. The resulting injectable star-shaped macromers are then crosslinked in the absence or the presence of calcium apatite to generate bulk polymer or polymer-mineral composite bone grafts. The modular design enables that each functional domain of the graft be independently modulated to optimize the overall performance of the graft. A detailed strategy is proposed to characterize the structural and mechanical properties, the degradation characteristics, the HA-nucleation capacity and the bioactivities of the synthetic bone graft in vitro. In addition, a rat femoral segmental defect model that takes into account the weight-bearing nature of the musculoskeletal tissue is utilized to evaluate the in vivo performance and viability of the synthetic graft. The extent and quality of the remodeling, vascularization and osteointegration of the graft as a function of polymer domain compositions, osteoconductive mineral contents and the exogenous signaling molecules locally released from the grafts will be analyzed by histology, microcomputed tomography, electron microscopy and torsion tests.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wang, Fei
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University of Massachusetts Medical School Worcester
Schools of Medicine
United States
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Liu, Pingsheng; Song, Jie (2016) Well-controlled ATRP of 2-(2-(2-Azidoethyoxy)ethoxy)ethyl Methacrylate for High-density Click Functionalization of Polymers and Metallic Substrates. J Polym Sci A Polym Chem 54:1268-1277
Kutikov, Artem B; Gurijala, Anvesh; Song, Jie (2015) Rapid prototyping amphiphilic polymer/hydroxyapatite composite scaffolds with hydration-induced self-fixation behavior. Tissue Eng Part C Methods 21:229-41
Kutikov, Artem B; Skelly, Jordan D; Ayers, David C et al. (2015) Templated repair of long bone defects in rats with bioactive spiral-wrapped electrospun amphiphilic polymer/hydroxyapatite scaffolds. ACS Appl Mater Interfaces 7:4890-901
Kutikov, Artem B; Song, Jie (2015) Biodegradable PEG-Based Amphiphilic Block Copolymers for Tissue Engineering Applications. ACS Biomater Sci Eng 1:463-480
Liu, Pingsheng; Skelly, Jordan D; Song, Jie (2014) Three-dimensionally presented anti-fouling zwitterionic motifs sequester and enable high-efficiency delivery of therapeutic proteins. Acta Biomater 10:4296-303
Xu, Jianwen; Feng, Ellva; Song, Jie (2014) Bioorthogonally cross-linked hydrogel network with precisely controlled disintegration time over a broad range. J Am Chem Soc 136:4105-8
Liu, Pingsheng; Domingue, Emily; Ayers, David C et al. (2014) Modification of Ti6Al4V substrates with well-defined zwitterionic polysulfobetaine brushes for improved surface mineralization. ACS Appl Mater Interfaces 6:7141-52
Skelly, Jordan D; Lange, Jeffrey; Filion, Tera M et al. (2014) Vancomycin-bearing synthetic bone graft delivers rhBMP-2 and promotes healing of critical rat femoral segmental defects. Clin Orthop Relat Res 472:4015-23
Zhang, Jing; Song, Jie (2014) Amphiphilic degradable polymers for immobilization and sustained delivery of sphingosine 1-phosphate. Acta Biomater 10:3079-90
Xu, Jianwen; Feng, Ellva; Song, Jie (2014) Renaissance of Aliphatic Polycarbonates: New Techniques and Biomedical Applications. J Appl Polym Sci 131:

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