Determining the Efficacy of a Novel Apatite-Based Antimicrobial Bone Scaffold for Craniofacial Surgical Applications

确定新型磷灰石抗菌骨支架在颅面外科应用中的功效

• 批准号: 10573777
• 负责人: Sujee Jeyapalina
• 金额: $ 42.35万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10573777
• 关键词: Accidents; Address; Adhesions; Allografting; Anti-Bacterial Agents; Antibiotics; Apatites; Autologous Transplantation; Autopsy; Bacteria; Bacterial Adhesion; Bone Injury; Bone Matrix; Bone Regeneration; Bone Substitutes; Bone Tissue; Bone Transplantation; Cadaver; Calcium ion; Caring; Cells; Cephalic; Clinical; Complex; Complication; Data; Debridement; Defect; Deposition; Development; Diameter; Evaluation; Exhibits; Family suidae; Fluorides; Goals; Harvest; High temperature of physical object; Histologic; Homeostasis; Hour; Human; Hydroxyapatites; Immobilization; Impairment; Implant; In Situ; In Vitro; Individual; Infection; Injury; Mature Bone; Mechanics; Medical; Medical Care Costs; Metals; Methods; Microbial Biofilms; Modeling; Muscle function; Muscular Atrophy; Musculoskeletal; Operative Surgical Procedures; Orthopedics; Osteogenesis; Outcome; Phenotype; Polymers; Porosity; Proliferating; Property; Public Health; Rattus; Research; Resistance; Risk; S phase; Secondary to; Site; Skeleton; Source; Staphylococcus aureus; Sterility; Structure; Surface; Surface Properties; Suspensions; Techniques; Temperature; Testing; Time; Tissues; Traumatic injury; Variant; Water fluoridation; Weight-Bearing state; X-Ray Computed Tomography; Zinc; allogenic bone transplantation; antimicrobial; biomaterial compatibility; bone; bone engineering; bone healing; bone repair; bone scaffold; chemical substitution; craniofacial; cranium; crystallinity; cytotoxicity; design; disability; early onset; efficacy evaluation; efficacy testing; fluor-hydroxylapatite; fluorapatite; healing; improved; in vivo; in vivo Model; in vivo evaluation; mechanical properties; microCT; musculoskeletal injury; novel; open wound; osteogenic; prevent; reconstruction; regenerative; research study; scaffold; skeletal; soft tissue; substantia spongiosa; tibia; vehicular accident; wound; wound cleaning; wound environment

PROJECT ABSTRACT / SUMMARY Traumatic musculoskeletal injuries commonly involve massive bone and soft tissue disruptions, with subsequent infection possibly developing as a frequent complication. This leads to multiple surgical debridements, which further increases the size of the defect. Surgical debridement is needed to achieve a clean wound required for successful bony reconstruction. Thus, addressing critical-size bone defects— which cannot be healed without replacing the lost bone with bone graft materials—is often delayed until wound homeostasis is obtained. Such delay may lead to secondary complications and life-long disability. Self-sourced or autograft bone is the “gold standard” among all graft materials, but the amount of bone sites available is limited. This produces insufficient graft material to fill critical-size defects, and such harvest requires secondary surgical sites. Decellularized and sterilized cadaveric or allograft bone commonly fails in bacterially contaminated wound environments. Engineered bone substitutes may provide a solution to this dilemma if the current limitations of these materials can be addressed, including their inability to match the mechanical strength, porosity, and bioactivity of autografts. Ideally, such engineered bone scaffolding materials should also possess antimicrobial properties. In the past, scaffold surfaces have been coated with antimicrobial/broad-spectrum antibiotics, but the rapid release or “burst effect” of these coatings only provides short-term protection, and sudden high antibiotic levels can be toxic to the local cells needed for healing. One other option could be to tailor bone scaffolds with intrinsic antimicrobial surface properties. The bone matrix crystalline hydroxyapatite (HA) is known for its biocompatibility, osteogenic properties, and bio-absorbability but lacks mechanical strength and controllable resorption properties. To improve the mechanical properties of HA, we have used both ionic chemical substitution and variation in temperatures to synthesize various apatite types. Our preliminary data revealed that fluoride substituted apatite (fluorapatite (FA)), when sintered above 11500C, produced improved mechanical strengths, including compression strengths and increased bone deposition in an in vivo model. We have also shown that when known antimicrobial metals are co-deposited and immobilized within the apatite crystals during the synthesis of FA, some combination of apatites exhibited improved antimicrobial properties without producing cell cytotoxicity. This proposal is designed to test one such apatite, zinc-doped fluorapatite (Zn-FA). Based on our preliminary data, it was hypothesized that an optimized molar percent zinc substituted porous fluorapatite scaffolds would have the potential to regenerate bone tissue within both sterile and infected sites. This hypothesis will be tested using three Specific Aims. Specific Aim 1 is designed to fabricate and test both mechanical and antimicrobial in vitro properties of various molar percent Zn substituted FA, Specific Aims 2 and 3 will test the efficacy of an optimized molar percent zinc substituted FA to generate bone tissues in contaminated and critical-size pockets, respectively.

项目摘要/总结 创伤性肌肉骨骼损伤通常涉及大块骨和软组织破坏， 感染可能发展为常见的并发症。这导致多次手术清创， 进一步增加了缺陷的尺寸。需要进行手术清创以获得所需的清洁伤口， 骨重建成功。因此，解决关键尺寸的骨缺损-如果不进行治疗， 用骨移植材料替换丢失的骨通常被延迟到获得伤口内环境平衡。等 延误可能导致继发性并发症和终身残疾。自体骨或自体骨移植是“黄金 在所有的移植材料中，“标准”是最好的，但骨部位的数量有限。这就产生了不足 移植物材料填充临界尺寸的缺损，并且这样的收获需要二次手术部位。脱细胞和 消毒的尸体或同种异体骨通常在细菌污染的伤口环境中失效。 工程骨替代物可能会提供一个解决这一困境，如果目前这些材料的局限性， 可以解决，包括它们无法匹配的机械强度，孔隙率和生物活性， 自体移植理想地，这种工程化骨支架材料还应具有抗微生物性质。在 过去，支架表面已经涂有抗菌/广谱抗生素，但快速释放 这些涂层的"爆发效应"仅提供短期保护， 对愈合所需的局部细胞有毒另一种选择是定制骨支架， 抗菌表面性能。骨基质结晶羟基磷灰石（HA）以其生物相容性而闻名， 成骨特性和生物吸收性，但缺乏机械强度和可控的再吸收 特性.为了改善HA的机械性能，我们使用了离子化学取代和 温度的变化来合成各种类型的磷灰石。我们的初步数据显示， 取代的磷灰石（氟磷灰石（FA）），当在1150 ℃以上烧结时，产生改进的机械强度， 包括体内模型中的压缩强度和增加的骨沉积。我们还表明， 当已知的抗微生物金属共沉积并固定在磷灰石晶体内时， 在FA合成中，磷灰石的某些组合表现出改善的抗微生物性能而不产生细胞 细胞毒本提案旨在测试一种这样的磷灰石，锌掺杂氟磷灰石（Zn-FA）。基于我们 根据初步数据，假设最佳摩尔百分比的锌取代多孔氟磷灰石 支架将具有在无菌和感染部位内再生骨组织的潜力。这 假设将使用三个特定目标进行检验。Specific Aim 1旨在制造和测试 不同摩尔百分比的Zn取代的FA的机械和抗微生物体外性质，具体目的2 和3将测试优化的摩尔百分比的锌取代的FA产生骨组织的功效， 污染和临界大小的口袋，分别。