3-D printed hyperelastic bone composites for bone regeneration and spine fusion

用于骨再生和脊柱融合的 3D 打印超弹性骨复合材料

• 批准号: 9084315
• 负责人: Erin L. HSU
• 金额: $ 31.68万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9084315
• 关键词: 3-Dimensional; 3D Print; Address; Adverse effects; Architecture; Arthrodesis; Behavior; Biological; Biomechanics; Bone Matrix; Bone Regeneration; Bone Transplantation; Ceramics; Clinical; Complex; Drops; Evaluation; FDA approved; Formulation; Geometry; Goals; Gold; Growth; Hydroxyapatites; Immune response; Individual; Inflammatory; Ink; Investigation; Marketing; Mechanics; Mesenchymal Stem Cells; Methods; Modeling; Morbidity - disease rate; Orthopedics; Osteogenesis; Pathology; Patients; Pharmaceutical Preparations; Porosity; Pre-Clinical Model; Printing; Procedures; Process; Property; Rattus; Research; Safety; Spinal; Spinal Fusion; Spine surgery; Stimulus; Surface; Surgeon; Techniques; Technology; Temperature; Translating; Variant; Vascularization; Vertebral column; Work; base; bioactive ceramic; bone; bone healing; clinical care; clinical practice; comparative; cost effective; design; flexibility; improved; individual patient; minimally invasive; new technology; novel; osteogenic; particle; pre-clinical; public health relevance; recombinant human bone morphogenetic protein-2; regenerative; scaffold; technology development; translational study

 DESCRIPTION (provided by applicant): The goal of this research is to transform clinical care for patients with degenerative and traumatic bone pathologies. Despite recent advances in bone graft technology, a major void remains for orthopaedic surgeons who perform procedures that require bone healing. Current biologics on the market, such as recombinant human bone morphogenetic protein-2 (rhBMP-2; INFUSE(tm)), are effective but are associated with adverse effects. Ceramics and demineralized bone matrices (DBM) are insufficiently effective as bone graft substitutes for spine fusion. Our goal is to develop an exogenous growth factor-free ceramic composite scaffold that is safe, easy to manipulate, and more effective at inducing bone formation and spine fusion than currently available products. To this end, our group has developed a unique 3D-printable hydroxyapatite (HA) ink that can be used to create a robust composite scaffold that not only promotes bone regeneration, but also has hyperelastic mechanical properties that improves functionality and delivery in both open and minimally invasive spine fusion procedures. This 3D-printed technology is easily scalable and facilitates incorporation of other bioactive factors or drugs, since ink synthesis, 3D-printing, and processing are carried out at ambient temperatures. In preliminary work, we developed a strategy to 3D-print a variation on this hyperelastic HA (hHA) that incorporates demineralized bone matrix (DBM) particles into the 3D-ink, which imparts an added osteoinductive stimulus from the native bioactive growth factors present within the DBM. The result is a flexible and elastic hHA-DBM composite that we believe is the basis for a highly effective bone graft substitute for both open and minimally invasive spine fusion procedures. With this proposal, we will 1) develop the optimal 3D-ink formulation and printing parameters for bone regeneration and evaluate the capacity of this hyperelastic bone composite (HBC) to elicit spine fusion in a rat spine fusion model; 2) compare its efficacy (bone regenerative and spine fusion capacities) with an established positive control (rhBMP-2; INFUSE(tm)); and 3) compare the mechanisms of pro-osteogenic action and inflammatory host response of the hyperelastic bone composite with that of rhBMP-2. We hypothesize that the resulting HBC will elicit comparable fusion rates and regenerative capacity to rhBMP-2, but will provoke a significantly lower inflammatory host response. This translational study aims to develop a technology that could modernize clinical care approaches, while advancing our understanding of the behavior and functionality of complex 3D-printed particle-based composites. Not only would this investigation lay the groundwork for a safe, efficacious, and cost-effective therapy for spinal arthrodesis, but the versatility of design and rapid rate of manufacturing would also allow for efficient customizabilit to individual patients. We expect that full development of this technology would transform clinical practice for patients with degenerative and traumatic conditions of the spine, and would ultimately translate to other orthopaedic and non-orthopaedic settings where bone regeneration is required.

 描述（由适用提供）：这项研究的目的是为具有退行性和创伤性骨骼病理的患者转变临床护理。尽管骨移植技术最近取得了进步，但对需要骨骼愈合的手术的骨科医生来说，仍然存在一个主要的空隙。市场上当前的生物制剂，例如重组人骨形态发生蛋白-2（RHBMP-2； Infuse（TM）），有效，但与广告效应有关。陶瓷，绝望地作为骨纹替代品用于脊柱融合。我们的目标是开发一个安全，易于操纵和在诱导的骨形成和脊柱融合时更有效的外源生长陶瓷复合支架。为此，我们的小组开发了一种独特的3D打印羟基磷灰石（HA）墨水，该墨水可用于创建可靠的复合支架，不仅可以促进骨骼再生，而且具有高弹性的机械性能，可改善开放式和微创脊柱融合过程中的功能性和传递。这项3D打印的技术易于扩展，并且有助于其他生物活性因子或药物的遗传，因为在环境温度下进行墨水合成，3D打印和加工。在初步工作中，我们制定了一种策略，以对这种超弹性HA（HHA）的3D印刷A变化，该策略将债务的骨基质（DBM）颗粒纳入3D-INK，从而在DBM中施加了来自天然生物活性生长因子的额外的骨诱导刺激。结果是一种柔性和弹性的HHA-DBM复合材料，我们认为这是开放和微创脊柱融合程序的高效骨移植替代物的基础。通过此提案，我们将1）开发用于骨再生的最佳3D-INK公式和打印参数，并评估这种超弹性骨复合材料（HBC）在大鼠脊柱融合模型中引起脊柱融合的能力； 2）将其效率（骨再生和脊柱融合能力）与已建立的阳性对照（RHBMP-2； Infuse（TM））进行比较； 3）比较热弹性骨复合材料与RHBMP-2的促稳态作用和炎症宿主反应的机制。我们假设由此产生的HBC将引起可比的融合速率和RHBMP-2的再生能力，但会引起炎症宿主的响应明显降低。这项翻译的研究旨在开发一种可以使临床护理方法现代化的技术，同时促进我们对复杂3D打印基于粒子的组成的行为和功能的理解。这项投资不仅为脊柱关节固定术的安全，高效且具有成本效益的治疗奠定了基础，而且设计和生产速度的多功能性也将允许对个别患者进行有效的自定义性定制。我们预计，这项技术的全面开发将改变脊柱退化和创伤性疾病的患者的临床实践，并最终转化为需要骨再生的其他骨科和非正交性环境。