Bone is the second most commonly transplanted tissue after blood (Giannoudis P, Dinopoulos H, Tsiridis E. Bone substitutes: An update. Injury, Int. J. Care Injured 2005; 36S:S20) with around 2.2 million grafting procedures performed worldwide each year (Lewandrowski K, Gresser J, Wise D, Trantol D. Bioresorbable bone graft substitutes of different osteoconductivities: a histologic evaluation of osteointegration of poly(propylene glycol-co-fumaric acid)-based cement implants in rats. Biomaterials 2000; 21:757; Van der Stok J, Van Lieshout E M M, El-Massoudi Y, Van Kralingen G H, Patka P. Bone substitutes in the Netherlands—A systematic literature review. Acta Biomaterialia 2010, In Press). Although autologous bone remains the standard of care for treatment of bone defects synthetic bone grafts have been developed to address the clinical drawbacks imposed by the harvesting procedure of autografts. Ceramic biomaterials such as calcium phosphate cements offer biocompatibility and osteoconductivity but have brittle mechanical properties (Kretlow JD, Young S, Klouda L, Wong M, Mikos A G. Injectable Biomaterials for Regenerating Complex Craniofacial Tissues. Adv Mater. 2009; 21:3368), can migrate from the implant site, and have slow resorption rates (Gilardino M, Cabiling D, Bartlett S. Long-term follow-up experience with carbonated calcium phosphate cement (Norian) for cranioplasty in children and adults. Plast Reconstr Surg. 2009; 123:983). Polymeric materials such as poly(methyl methacrylate) (PMMA) can be injected into the defect. However, PMMA polymerizes at high temperatures causing tissue necrosis, and generates stress-shielding which accelerates resorption of the neighboring bone (Ni G, Lu W, Chiu P, Wang Y, Li Z, Zhang Y, Xu B, Deng L, Luk K. Mechanical properties of femoral cortical bone following cemented hip replacement. Journal of Orthopaedic Research 2007; 25:1408). Polyurethane (PUR) networks from lysine polyisocyanates have been shown to support cellular proliferation and differentiation (Guelcher S A, Srinivasan A, Dumas J E, Didier J E, McBride S, Hollinger J O. Synthesis, mechanical properties, biocompatibility, and biodegradation of polyurethane networks from lysine polyisocyanates. Biomaterials 2008; 29:1762), to function as injectable delivery systems and to degrade to non-cytotoxic compounds (Hafeman A, Li B, Toshikata Y, Zienkiewicz K, Davidson J M, Guelcher S A. Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration. Pharmaceutical Research 2008; 25:23877).
Efforts have been made to develop composites comprising polyurethane materials combined with particulates (e.g., bone particles and ceramic biomaterials such as calcium phosphate). For example, bone particles incorporated in polyurethane materials can act as a reinforcement material as well as a porogen that guides cellular infiltration.
Interfacial binding and particulates loading are both critical to mechanical properties and cellular infiltration rates. The present application discloses that composite materials with covalent bonding between particulates (e.g., bone particles and ceramic biomaterials such as calcium phosphate) and polyurethane materials, and/or high particulate content show increased mechanical properties while preserving osteoconductive biological properties. Inventive compositions (e.g., composites) described here can be utilized in various orthopedic applications.
USPTO Backgrounds
USPTO Backgrounds