Sunday, May 18, 2025
5/18/2025
ABSORBABLE, SELF-SETTING BONE CEMENT - DESCRIPTION (provided by applicant): Since early development of polymethyl methacrylate bone cement (PMMA-BC), there have been many efforts to develop alternative compositions to circumvent some of its clinical shortcomings, which include (1) monomer cytotoxicity; (3) inability to form strong joint at the tissue-cement interface; and (3) being a permanent, non-absorbable implant, which may induce infection. Among the major alternatives to PMMA-BC is the self-setting calcium phosphate bone cement (CPC), which suffers from being fragile and highly susceptible to fracture. Acknowledging PMMA-BC and CPC shortcomings and recent commercialization of absorbable cyanoacrylate tissue adhesive formulations prompted the pursuit of the proposed program. And its Phase I objective is to demonstrate the feasibility of developing a self-setting absorbable, bioactive, cyanoacrylate phosphate-based composite as a preferred alternative to non-absorbable PMMA-BC. Accordingly, Phase I plans entail (1) using initial results acquired in this laboratory on self-setting, absorbable, cyanoacrylate phosphate-based composites (SCC-P) to prepare five candidate systems and selecting the most promising SCC-P as per a comparative in vitro evaluation against a typical PMMA-BC; (2) repeating the study on SCC-P systems using mixtures of a phosphate and a silicate to produce three additional candidates comprising phosphate and silicate components (SCC-PS), selecting the most promising SCC-PS, and conducting a comparative in vitro evaluation against a typical PMMA-BC; (3) using the two selected SCC-P and SCC-PS candidates to determine their in vivo efficacies, relative to a PMMA-BC control, in repairing a typical bone defect in rabbits; (4) reinforcing the selected SCC-P and SCC-PS candidates with warp-knitted absorbable mesh and determining the in vitro physical properties of the reinforced composites before and after aging; and (5) analyzing the in vitro and in vivo performance data and selecting a candidate for Phase II study. Plans for Phase II study will include (1) optimization of the selected SCC-P or SCC-SP system into an absorbable, bioactive, self-setting bone cement (ABS-BC) with and without knitted mesh reinforcement, relying on in vitro physical and mechanical properties as cementing/defect filling materials, with or without absorbable, mesh reinforcements; (2) completion of development, scale-up, sterilization, and packaging studies; (3) completion of the validation studies of all processes; (4) development of a suitable animal model for at least three clinical indications and demonstrating the ABS-BC in vivo efficacy using selected animal models; and (5) securing a marketing partner to develop plans for the manufacturing and marketing of the ABS-BC. PUBLIC HEALTH RELEVANCE: Developing absorbable, self-setting, bioactive cyanoacrylate-based composites comprising inorganic silicate and/or phosphate microparticles with or without reinforcement with an absorbable knitted mesh will provide the clinical community with novel biomaterials for use as preferred alternatives to the non-absorbable polymethyl methacrylate bone cement and in repairing or substituting cranial and maxillofacial bone defects through guided bone regeneration.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).