Human Bone Engineering and Resorption in a Novel Mineralized Collagen Scaffold

新型矿化胶原蛋白支架中的人体骨骼工程和吸收

基本信息

批准号：
9105156
负责人：
Justine Chia Lee
金额：
--
依托单位：
VA GREATER LOS ANGELES HEALTHCARE SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9105156
关键词：
Address Adipose tissue Adverse effects Animal Model Autologous Biocompatible Materials Biology Biomedical Engineering Bone Marrow Bone Morphogenetic Proteins Bone Regeneration Bone Resorption Bone Transplantation Cells Cephalic Clinical Collagen Coupling Craniofacial Abnormalities Custom Data Defect Dose Down-Regulation Engineering Environment Equilibrium Excision GAG Gene Glycosaminoglycans Goals Gold Growth Healed Human Implant In Vitro Infection Investigation Laboratories Length of Stay Limb structure Long-Term Effects Longevity Maxilla Mediating Mesenchymal Stem Cells Methods Molecular Morbidity - disease rate Mus Organ Transplantation Oryctolagus cuniculus Osteoclasts Osteogenesis Patients Peripheral Blood Mononuclear Cell Population Process Reagent Receptor Signaling Regenerative Medicine Repeat Surgery Reporting Research Personnel Signal Pathway Signal Transduction Skeleton Source Stromal Cells Swelling System TNFSF11 gene Technology Testing Therapeutic Time Tissue Engineering Translations Trauma Traumatic injury Tumor necrosis factor receptor 11b Up-Regulation Veterans Work base bone bone engineering bone healing bone morphogenetic protein 2 bone morphogenetic protein receptors chronic pain clinical application combat functional restoration healing implantation in vivo innovation nanoparticulate novel osteoclastogenesis osteogenic pre-clinical public health relevance reconstruction response scaffold skeletal soft tissue success tumor

项目摘要

DESCRIPTION (provided by applicant): Large defects of the craniofacial skeleton and extremities occur frequently in our Veterans and may result in functional deficits that require extensive reconstruction. Although autologous bone grafting is the current gold standard for reconstruction of skeletal defects, significant donor sit morbidity including chronic pain, infection, repeated surgeries, and prolonged hospital stays may ensue thus creating a significant need for alternative methods of skeletal replacement. The success of tissue engineering for bone regeneration depends on the optimal interplay of scaffold technology, growth factors, and cellular material in a deliverable fashion. Two barriers to true clinical translation are the variable side effect profiles of exogenous growth factors delivered at high concentrations and the acceptance of laboratory fabricated bone by the host environment. Clinically, supraphysiologic doses of osteogenic growth factors, such as bone morphogenetic protein-2, are utilized as a supplement or replacement for bone grafting procedures. Although bone healing can be accomplished to a certain degree, untoward effects such as soft tissue swelling, ectopic bone formation, resorption of adjacent bone, and long term effects on maxillary growth have all been reported. Our laboratory has previously demonstrated that mesenchymal stem cells can be induced to undergo osteogenesis on three-dimensional scaffolds. Osteogenesis was stimulated regardless of species (mouse, rabbit, or human) or the source of mesenchymal stem cells (bone marrow or adipose). In addition, scaffolds carrying osteogenic cells can be utilized to heal critical sized defects of the rabbit cranial skeleton. However, similr to studies from other investigators, the long term stability of engineered bone after implantation is limited by resorption over time. In this application, we focus on delineating the osteogenic mechanism of a novel, nanoparticulate mineralized collagen glycosaminoglycan scaffolds that imparts efficient osteogenesis of both primary rabbit bone marrow stromal cells and primary human mesenchymal stem cells without additional bone morphogenetic protein stimulation. We propose to investigate the coupling of osteogenesis and osteoclastogenesis in this system with both in vitro and in vivo cranial defect studies.

描述（由申请人提供）：颅面骨骼和四肢的大缺陷在我们的退伍军人中经常发生，并可能导致需要广泛重建的功能缺陷，尽管自体骨移植是当前骨骼缺陷重建的黄金标准，但显着的供体发病率包括慢性疼痛、感染、反复。手术和住院时间延长可能会随之而来，因此迫切需要替代骨骼替代方法。骨再生组织工程的成功取决于支架技术、生长因子和细胞材料的最佳相互作用。以可传递的方式进行真正的临床转化的两个障碍是外源生长因子的可变副作用。临床上，超生理剂量的成骨生长因子（例如骨形态发生蛋白-2）被用作骨移植手术的补充或替代品，尽管可以实现骨愈合。在一定程度上，诸如软组织肿胀、异位骨形成、邻近骨吸收以及对上颌骨生长的长期影响等不良影响均已被报道，我们的实验室之前已经证明可以诱导间充质干细胞。无论物种（小鼠、兔子或人类）或间充质干细胞的来源（骨髓或脂肪）如何，骨生成都会受到刺激。此外，携带成骨细胞的支架可用于愈合临界尺寸。然而，与其他研究人员的研究类似，植入后工程骨的长期稳定性受到随时间的吸收的限制。在本申请中，我们重点描述成骨。一种新型纳米颗粒矿化胶原糖胺聚糖支架的机制，该支架可以使原代兔骨髓基质细胞和原代人间充质干细胞有效成骨，而无需额外的骨形态发生蛋白刺激，我们建议研究该系统中成骨和破骨细胞生成的耦合。体外和体内颅骨缺陷研究。