An Injectable Phosphate Releasing Bone Tissue Construct Encapsulating Adipose-Derived Stem Cells and Diphosphate Cleaving Enzymes to Promote Biomineralization in Critical Size Bone Defects

一种可注射的磷酸盐释放骨组织构建体，封装脂肪干细胞和二磷酸裂解酶，以促进临界尺寸骨缺损的生物矿化

• 批准号: 538864-2019
• 负责人: Tabrizian, Maryam
• 金额: $ 18.63万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Collaborative Health Research Projects
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=697789
• 关键词: Injectable; Phosphate; Releasing; Bone; Tissue

Critical size bone defects (CSBD) are non-healing bone injuries that require a therapeutic intervention to induce bone formation. These injuries occur due to trauma, removal of tumors, developmental anomalies, and infections. Impaired bone healing, including delayed union or non-union, accounts for 150,000 to 200,000 hospitalizations in Canada generating a $12 to $18 B/y burden on the health care system. The current golden standard is to graft autologous bone from the patients iliac crest onto the defect. The need to create a second surgical intervention increases the risk of post-surgical complications and wound infections, and requires longer hospitalization. An injectable therapeutic modality that can be administered using minimally invasive surgery will reduce risk of infection, time of hospitalization and\ surgical costs. We successfully demonstrated, that injectable chitosan sponges developed in\ our laboratory, are biocompatible, and completely biodegrade within 60 days. The addition of enzymes to the chitosan sponges provided a constant release of phosphate ions, which significantly increased biomineralization in pre-osteoblast MC3T3 cells. Further, a high encapsulation efficiency of osteogenic factors in the sponge and its controlled release over a period of 30 days could be achieved. The encapsulation of both MC3T3 and Adipose-Derived Stem Cells (ASCs) indicated the suitability of the scaffold for cells survivability, proliferation and differentiation. Herein, we propose to investigate the sponge as a delivery system and as a 3D-scaffold for ASCs encapsulation, enzymes and osteogenic factors, and ultimately as a tissue construct for in vivo biomineralization in CSBD. To translate this promising technology platform to clinics, it is imperative to validate the sponge in relevant animal model of CSBD. This opportunity will be offered by our success in this CHRP proposal in partnership with industry and commercialization specialists involved in this proposal.

临界尺寸骨缺损（CSBD）是需要治疗干预以诱导骨形成的非愈合骨损伤。这些伤害是由于创伤，肿瘤的去除，发育异常和感染而引起的。骨骼治疗受损，包括延迟工会或非工会，在加拿大占150,000至200,000的住院治疗，产生了12美元 保健系统上的$ 18 b/y负担。目前的黄金标准是将患者的自体骨从患者的缺陷上移植到缺陷上。进行第二次手术干预的需求增加了手术后并发症和伤口感染的风险，并且需要更长的住院治疗。可以使用微创手术进行的可注射治疗方式可以降低感染的风险，住院时间和手术费用。我们成功证明了在我们的实验室中开发的可注射壳聚糖海绵是生物相容性的，并且在60天内完全生物降解。在壳聚糖海绵中添加酶提供了磷酸离子的持续释放，从而显着增加了骨细胞前MC3T3细胞中的生物矿化。此外，可以实现海绵中成骨因子的高封装效率及其在30天内的受控释放。 MC3T3和脂肪衍生的干细胞（ASC）的封装表明支架对细胞生存能力，增殖的适用性 和分化。在本文中，我们建议将海绵作为递送系统进行研究，并作为ASC封装，酶和成骨因子的3D支柱，最终是CSBD中体内生物矿化的组织构建体。为了将这个有希望的技术平台转换为诊所，必须在CSBD相关的动物模型中验证海绵。我们在这项CHRP提案中的成功将为这一机会提供与参与该提案的行业和商业化专家合作的成功。