Absorbable, Self-setting Bone Cement

可吸收、自凝骨水泥

• 批准号: 7745263
• 负责人: SHALABY W SHALABY
• 金额: $ 10万
• 依托单位: POLY-MED, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-07 至 2010-06-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7745263
• 关键词: Absorbable Implants; Aging; Animal Model; Biocompatible Materials; Bone Cements; Bone Regeneration; Buffers; Calcium; Cephalic; Clinical; Communities; Cyanoacrylates; Data; Defect; Development; Drug Formulations; Evaluation; Fracture; In Vitro; Infection; Joints; Laboratories; Marketing; Mechanics; Oryctolagus cuniculus; Performance; Phase; Phase II Clinical Trials; Polymethyl Methacrylate; Process; Property; Psychological reinforcement; Relative (related person); Secure; Silicates; Sodium Chloride; Solutions; Sterilization for infection control; System; Tissue Adhesives; Tissues; absorption; base; bone; calcium phosphate; commercialization; comparative; cytotoxicity; in vivo; inorganic phosphate; maxillofacial; monomer; novel; physical property; programs; public health relevance; repaired; scale up; validation studies

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.

描述（由申请人提供）：自聚甲基丙烯酸甲酯骨水泥（PMMA-BC）的早期开发以来，已经做出了许多努力来开发替代组合物以规避其一些临床缺点，其中包括（1）单体细胞毒性； (3)组织-骨水泥界面不能形成牢固的接合； (3) 是永久性的、不可吸收的植入物，可能会引起感染。 PMMA-BC 的主要替代品之一是自凝磷酸钙骨水泥 (CPC)，它易碎且极易断裂。认识到 PMMA-BC 和 CPC 的缺点以及最近可吸收氰基丙烯酸酯组织粘合剂配方的商业化，促使我们实施所提出的计划。其第一阶段的目标是证明开发一种自固化可吸收、生物活性、氰基丙烯酸酯磷酸盐基复合材料作为不可吸收 PMMA-BC 的首选替代品的可行性。因此，第一阶段计划包括（1）利用本实验室获得的自凝、可吸收、氰基丙烯酸酯磷酸盐基复合材料（SCC-P）的初步结果来制备五个候选系统，并根据与典型 PMMA-BC 的体外比较评估选择最有前途的 SCC-P； (2) 使用磷酸盐和硅酸盐的混合物重复对SCC-P系统的研究，以产生另外三种包含磷酸盐和硅酸盐组分的候选物(SCC-PS)，选择最有前途的SCC-PS，并与典型的PMMA-BC进行体外比较评估； (3) 使用两个选定的 SCC-P 和 SCC-PS 候选物来确定它们相对于 PMMA-BC 对照在修复兔子典型骨缺损方面的体内功效； (4)用经编可吸收网增强选定的SCC-P和SCC-PS候选材料，并测定增强复合材料老化前后的体外物理性能； (5)分析体外和体内性能数据并选择II期研究的候选者。 II 期研究计划将包括 (1) 将选定的 SCC-P 或 SCC-SP 系统优化为具有或不具有编织网状增强材料的可吸收、生物活性、自凝骨水泥 (ABS-BC)，依赖于作为骨水泥/缺陷填充材料的体外物理和机械性能，具有或不具有可吸收的网状增强材料； (2) 完成开发、放大、灭菌和包装研究； (3) 完成所有工艺的验证研究； (4) 开发适合至少三种临床适应症的动物模型，并使用选定的动物模型证明 ABS-BC 的体内功效； (5) 确保营销合作伙伴制定 ABS-BC 的制造和营销计划。 公共健康相关性：开发可吸收、自凝、生物活性氰基丙烯酸酯基复合材料，包含无机硅酸盐和/或磷酸盐微粒，有或没有可吸收针织网加固，将为临床界提供新型生物材料，用作不可吸收聚甲基丙烯酸甲酯骨水泥的首选替代品，并用于修复或替代 通过引导骨再生修复颅骨和颌面部骨缺损。