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

基本信息

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
项目类别：
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

项目摘要

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/摘要创伤性肌肉骨骼损伤通常涉及大量骨骼和软组织破坏，随后可能会出现感染作为常见并发症，这会导致多次手术清创。需要进行手术清创以达到清洁伤口的目的。因此，解决了临界尺寸的骨缺损——如果不这样做就无法治愈。用骨移植材料替代丢失的骨——通常会延迟到伤口达到稳态为止。延误可能会导致继发性并发症和终生残疾。自体或自体移植骨是“黄金”。所有移植材料中的“标准”，但可用的骨位点数量有限，这导致骨量不足。移植材料来填充临界尺寸的缺陷，并且这种收获需要二次手术部位。消毒的尸体骨或同种异体移植骨在细菌污染的伤口环境中通常会失败。如果这些材料目前的局限性，工程骨替代品可能会解决这一困境可以解决的问题，包括它们无法匹配机械强度、孔隙率和生物活性理想情况下，这种工程骨支架材料还应具有抗菌特性。过去，支架表面涂有抗菌/广谱抗生素，但快速释放这些涂层的“爆发效应”或“爆发效应”仅提供短期保护，并且抗生素水平突然升高可能会导致另一种选择可能是定制具有内在功能的骨支架。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吸收为了提高HA的机械性能，我们使用了离子化学取代和我们的初步数据显示，合成各种磷灰石类型的温度变化。取代磷灰石（氟磷灰石 (FA)）在 11500C 以上烧结时，可提高机械强度，包括体内模型中的压缩强度和增加的骨沉积。当已知的抗菌金属在磷灰石晶体中共沉积并固定时 FA 的合成，磷灰石的某些组合显示出改善的抗菌特性，而不产生细胞该提案旨在测试一种磷灰石，即掺锌氟磷灰石 (Zn-FA)。初步数据表明，优化的摩尔百分比锌取代多孔氟磷灰石支架将具有在无菌和感染部位再生骨组织的潜力。将使用三个特定目标来测试假设。特定目标 1 旨在构建和测试这两个目标。不同摩尔百分比的 Zn 取代 FA 的机械和抗菌体外特性，具体目标 2 3 将测试优化的锌取代 FA 摩尔百分比在体内生成骨组织的功效分别是受污染的和临界尺寸的口袋。