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（由申请人证明）：尽管骨移植技术最近，这是对骨移植技术的临床护理的目的。 （RHBMP-2；输液（TM）效应。独立的3D-胶质羟基磷灰石（HA）墨水，可以创建一个可靠的复合脚手架，使骨骼再生弹性机械性能在开放和微创脊柱融合过程中改善和传递，可缩放和促进其他生物活性因子。或药物，由于墨水合成和在初步工作中进行的处理。 -INK从DBM中赋予的天然Tive生长因子添加了牙本质的刺激。程序。 2; Infuse（TM）和3）比较了骨化作用的机制和假设的炎症宿主反应与RHBMP-2这可以使临床护理方法现代化，同时我们对复杂的3D打印粒子复合材料的行为和功能的理解不仅为安全，有效且具有成本效益的脊髓关节疗法，而且还为设计和制造速率的多功能性也将使对个人有效，我们期望这项技术对脊柱退行性创伤性的患者进行全面发展，并最终转化为其他骨骼上的骨科和非骨科医生。