Validating a new, translatable biomaterial for healing critical bone defects

验证一种用于治疗严重骨缺损的新型可翻译生物材料

• 批准号: 10580837
• 负责人: David A Prawel
• 金额: $ 19.41万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580837
• 关键词: 3D Print; Acceleration; Address; Affect; Allogenic; American; Biocompatible Materials; Biodegradation; Biomimetics; Blood Vessels; Bone Development; Bone Growth; Bone Regeneration; Clinical; Clinical Trials; Compressive Strength; Defect; Development; Drug Delivery Systems; Electroplating; Engineering; Excision; Formulation; Frequencies; Funding; Future; Goals; Grain; Growth Factor; Healthcare; Human; Implant; Infection; Life; Literature; Malignant Neoplasms; Mechanics; Medicine; Metals; Methods; Minerals; Modeling; Modulus; Mothers; Motivation; Nature; Nutrient; Orthopedics; Osseointegration; Osteogenesis; Outcome; Outcome Study; Patients; Phase; Pilot Projects; Porosity; Powder dose form; Process; Property; Repeat Surgery; Research; Research Personnel; Sampling; Sheep; Structure; Testing; Thinness; Tissue Engineering; Trace Elements; Translating; Trauma; Variant; Vascularization; Work; bone; bone healing; calcium phosphate; clinical translation; density; design; economic cost; experience; fabrication; functional outcomes; healing; improved; in vivo; limb loss; mechanical properties; mineralization; osteogenic; remediation; sample fixation; scaffold; standard care; success; translation to humans; translational potential; tricalcium phosphate; virtual; wasting

PROJECT SUMMARY/ABSTRACT Poor healing of large bone defects remains one of the biggest challenges in human orthopedic medicine, affecting more than 1.5 million Americans per year and often leading to infections and other clinical complications, reoperations, poor functional outcomes, and ultimately, all too often, limb loss. The current gold- standard treatment is large metal plate fixation, which is prone to infection and remains in the patient’s body for life. Thus, there is a critical need to address this challenge in human medicine. Researchers have been working on tissue engineered solutions for decades, using scaffolds made of tri-calcium-phosphate (TCP) due to their excellent bioactivity (osteoinduction, osteoconduction and osseointegration), tunable degradation rate and promising drug delivery capabilities. However, despite excellent bone regeneration properties, these scaffolds are not strong enough to support significant loads, especially in critical defects. A viable solution to healing critical defects requires fast, natural bone growth, vascular development, and mechanical integrity to support loads while the new bone grows. Numerous trace elements that are found in bone, such as Zn, Mg, Sr, Si and Mn, have been added to TCP scaffolds (a.k.a. “doping”) to improve mechanical properties and bioactivity, and accelerate new bone formation. Many other trace elements may also play a role in bone development but have yet to be explored. Unfortunately, an intractable combination of studies is required when one considers all combinations of trace elements found in bone and ideal concentrations of each. No amount of funding will be enough to evaluate all these combinations in bone healing. This virtually unlimited set of variants leads to a hypothesis that natural bone may already contain the ideal mineral composition, after many millions of years of trial and error. Rather than trying to re-engineer the mineral composition of bone, this proposal seeks to fabricate and fully characterize bone regeneration scaffolds composed of naturally derived bone powder and test these scaffolds in a pilot ovine in vivo study. We lean on mother nature to provide a possible solution. The novelty of our approach is that we’re testing a new biomimetic biomaterial. No study to date has tested naturally derived bone mineral in bone regeneration scaffolds. Our approach depends on a naturally derived material that would be associated with lower regulatory burden, therefore, should be easier to translate to human medicine. We hope to extend this work to develop similar methods using naturally derived human bone mineral for healing human critical defects. If successful, this project could enable higher porosity structures to accelerate bioactivity and vascularization, both of which would have a significant impact on critical defect bone healing. Our long-term goal is to enable removal of all metal fixation, leaving only endogenous bone as we expect our naturally derived biomaterials to be replaceable by native bone as our future work accelerates bone growth.

项目概要/摘要 大骨缺损的愈合不良仍然是人类骨科医学面临的最大挑战之一， 每年影响超过 150 万美国人，并经常导致感染和其他临床症状 并发症、再次手术、功能不良，最终常常导致肢体丧失。目前的黄金—— 标准治疗方法是大金属板固定，容易发生感染，且会长期留在患者体内 生活。因此，迫切需要解决人类医学中的这一挑战。研究人员一直在努力 数十年来一直致力于组织工程解决方案，使用磷酸三钙 (TCP) 制成的支架，因为它们具有以下优点： 优异的生物活性（骨诱导、骨传导和骨整合）、可调节的降解速率和 有前途的药物输送能力。然而，尽管这些支架具有优异的骨再生特性， 强度不足以支撑重大负载，尤其是在严重缺陷的情况下。治愈危重患者的可行解决方案 缺陷需要快速、自然的骨骼生长、血管发育和机械完整性来支撑负载，同时 新骨头生长。骨骼中含有多种微量元素，如 Zn、Mg、Sr、Si 和 Mn， 添加到 TCP 支架（又名“掺杂”）中以提高机械性能和生物活性，并加速 新骨形成。许多其他微量元素也可能在骨骼发育中发挥作用，但尚未得到证实。 探索过。不幸的是，当考虑所有组合时，需要进行棘手的研究组合 骨骼中发现的微量元素以及每种元素的理想浓度。任何资金都不足以 评估所有这些组合在骨愈合中的作用。这组几乎无限的变体导致了一个假设： 经过数百万年的反复试验，天然骨骼可能已经含有理想的矿物质成分。 该提案不是试图重新设计骨骼的矿物质成分，而是寻求制造并充分 表征由天然骨粉组成的骨再生支架并进行测试 试点绵羊体内研究中的支架。我们依靠大自然提供可能的解决方案。新奇之处 我们的方法之一是我们正在测试一种新的仿生生物材料。迄今为止还没有研究测试过自然衍生的 骨再生支架中的骨矿物质。我们的方法依赖于一种自然衍生的材料 与较低的监管负担相关，因此应该更容易转化为人类医学。我们 希望扩展这项工作，开发类似的方法，使用天然来源的人体骨矿物质进行治疗 人类的严重缺陷。如果成功，该项目可以实现更高孔隙率的结构，从而加速生物活性 和血管化，这两者都会对关键缺损骨的愈合产生重大影响。我们的长期 目标是能够去除所有金属固定，只留下内源性骨，正如我们期望的那样 随着我们未来的工作加速骨骼生长，生物材料将被天然骨骼替代。

项目成果

Robocasting of Ceramic Fischer-Koch S Scaffolds for Bone Tissue Engineering.

用于骨组织工程的陶瓷Fischer-Koch S支架的机器人。

• DOI: 10.3390/jfb14050251
• 发表时间: 2023-04-30
• 期刊: JOURNAL OF FUNCTIONAL BIOMATERIALS
• 影响因子: 4.8
• 作者: Baumer, Vail;Gunn, Erin;Riegle, Valerie;Bailey, Claire;Shonkwiler, Clayton;Prawel, David
• 通讯作者: Prawel, David