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.

项目摘要/摘要 大骨缺陷的治愈不良仍然是人类骨科医学中最大的挑战之一， 每年影响超过150万美国人，并且经常导致感染和其他临床 并发症，重新运作，功能不良的结果，最终频繁的肢体损失。当前的金 - 标准处理是大型金属板固定，它容易感染，并且仍留在患者的身体中 生活。这是在人类医学中应对这一挑战的迫切需要。研究人员一直在工作 几十年来，使用由三钙 - 磷酸三磷酸盐（TCP）制成的支架，因此 优异的生物活性（骨诱导，破骨和骨整合），可调节降解率和 有希望的药物输送能力。但是，尽管骨骼再生特性很高，但这些脚手架 不足以支持重大负载，尤其是在关键缺陷中。可行的解决方案，以治愈关键 缺陷需要快速自然的骨骼生长，血管发育和机械完整性，以支持负载 新的骨头长大。在骨骼中发现的许多痕量元素，例如Zn，Mg，Sr，Si和Mn，具有 被添加到TCP支架（又称“掺杂”）中，以提高机械性能和生物活性，并加速 新的骨形成。许多其他痕量元素也可能在骨骼发育中发挥作用，但尚未 探索。不幸的是，当人们认为所有组合时，都需要进行棘手的研究组合 在骨骼和理想浓度中发现的微量元素。没有足够的资金足以 评估骨愈合中的所有这些组合。这种几乎无限的变体集导致了一个假设 经过数百万年的反复试验，天然骨可能已经包含理想的矿物组成。 该提案不是试图重新设计骨骼的矿物质成分，而是试图完全制造和完全 表征由自然衍生的骨粉组成的骨再生支架，并测试这些 脚手架在体内研究中的脚手架。我们依靠大自然母亲提供可能的解决方案。新奇 我们的方法是我们正在测试一种新的仿生生物材料。迄今为止，没有研究自然得出 骨骼再生支架中的骨矿物质。我们的方法取决于一种自然派生的材料 因此，与较低的监管伯恩相关，应该更容易转化为人类医学。我们 希望扩展这项工作，以使用自然衍生的人骨矿物质来开发类似的方法 人类批判缺陷。如果成功，该项目可以使较高的孔隙度结构加速生物活性 和血管形成，两者都会对关键缺陷骨愈合产生重大影响。我们的长期 目标是启用所有金属固定，只留下内源性骨头，因为我们期望天然衍生 随着我们未来的工作加速骨骼生长，生物材料可被本地骨骼替代。

项目成果

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

• 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