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Autologous Stem Cell-Augmented Mandibular Distraction Osteogenesis

自体干细胞增强下颌牵引成骨

基本信息

批准号：
8855030
负责人：
Zongyang Sun
金额：
$ 34.65万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8855030
关键词：
Absorbable Gelatin Sponge Animal Model Animals Aspirate substance Autologous Autologous Transplantation Biomechanics Blood Platelets Bone Marrow Bone Marrow Transplantation Bone Regeneration Bone Transplantation Cell Proliferation Cell Survival Cell Transplantation Cells Coculture Techniques Congenital Abnormality Control Animal Data Defect Deformity Distraction Osteogenesis Effectiveness Exclusion Family suidae Fibrinogen Fracture Gel Germ Cells Goals Harvest Health Human In Vitro Infection Injection of therapeutic agent Injury Intervention Jaw Lead Lesion Life Mandibular distraction Marrow Mechanical Stimulation Mechanics Mesenchymal Stem Cell Transplantation Mesenchymal Stem Cells Methods Mission Modality Modeling Molecular Natural regeneration Operative Surgical Procedures Osteogenesis Osteotomy Patients Phase Plasma Population Protocols documentation Regenerative Medicine Risk Scheme Site Speed Stem cells Stretching Testing Thrombin Time Tissue Engineering Transplantation Treatment Failure Undifferentiated X-Ray Computed Tomography angiogenesis base bone bone cell clinical application clinically relevant craniofacial distraction expectation improved in vivo non-compliance osteogenic repaired scaffold skeletal standard care tibia tumor

项目摘要

DESCRIPTION (provided by applicant): Large craniofacial skeletal defects or deficiencies significantly compromise patient's life and remain challenging to treat. Distraction osteogenesis (DO), a mechanically-induced endogenous bone-regeneration approach, has been used as a major treatment modality. Though reliable in bone regeneration, the current DO approach is inefficient because it relies mostly on mechanical stimulation, hence requiring a substantially prolonged treatment time with heightened risks of infection, appliance breakage, noncompliance, and treatment failures. Consistent with the current NIDCR's mission on tissue engineering and regenerative medicine, this project has an overall goal to augment jaw bone regeneration by using mechanical stimulation combined with autologous stem cell-based tissue engineering approaches. The hypothesis is that mandibular DO can be significantly accelerated by the introduction of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) through scaffolds before distraction and booster BM-MSC injections during the consolidation phase. Young pigs, closely relevant to young humans who constitute the population commonly receiving craniofacial DO treatments, will be used. The project will first establish baseline parameters in control animals using our validated pig mandibular DO model. Aim 1 studies will then determine two critical aspects of introducing cells to the DO site, i.e., the use of undifferentiated or osteogenic-differentiated BM-MSCs, and the inclusion or exclusion of bone marrow-derived endothelial progenitor cells (BM-EPCs). Both of these aspects are highly relevant to osteogenesis and angiogenesis needed for bone regeneration, but no study to date has concurrently evaluated them in a DO site. Bone regeneration following cell transplantation will be compared to the baseline parameters derived from the controls in order to identify the lead osteogenic promoting combination. Next, the project will determine whether booster injection of BM-MSCs during the consolidation phase further improves bone regeneration (Aim 2). Bone regeneration following initial cell transplantation together with booster injections will e compared to that only with initial cell transplantation. The effects of using autologous platelet-rich plasma (PRP) to carry BM-MSCs for injections will also be determined by comparing the DO sites with PRP included in the injections versus DO sites without PRP. The combined data from Aim 1 and 2 will be employed to create an optimal treatment scheme to be evaluated in an accelerated DO protocols with a faster distraction and a shorter consolidation (Aim 3). These studies will determine whether or not an optimized DO with autologous stem cell intervention can substantially shorten (by several weeks) the DO treatment time while achieving similar quality and quantity of bone regeneration, compared to regular DO without cell augmentation. Overall, this project has the potential to establish a new paradigm for the management of large craniofacial bone deficiencies or defects using distraction osteogenesis.

描述（由申请人提供）：大的颅面骨骼缺陷或缺陷严重危及患者的生活，仍然具有挑战性的治疗。牵引成骨（DO），机械诱导的内源性骨再生方法，已被用作主要的治疗方式。虽然骨再生可靠，但目前的DO方法效率低下，因为它主要依赖于机械刺激，因此需要显著延长的治疗时间，感染、器械断裂、不依从和治疗失败的风险增加。与目前NIDCR在组织工程和再生医学方面的使命一致，该项目的总体目标是通过使用机械刺激结合自体干细胞组织工程方法来增强颌骨再生。该假设是，下颌骨DO可以显着加速通过引入自体骨髓源性间充质干细胞（BM-MSC）通过支架前牵引和助推器BM-MSC注射在巩固阶段。将使用与构成通常接受颅面DO治疗的群体的年轻人密切相关的年轻猪。该项目将首先使用我们验证的猪下颌骨DO模型在对照动物中建立基线参数。目标1研究将确定将细胞引入DO位点的两个关键方面，即，使用未分化或成骨分化的BM-MSC，以及包括或排除骨髓衍生的内皮祖细胞（BM-EPCs）。这两个方面都与骨再生所需的骨生成和血管生成高度相关，但迄今为止还没有研究在DO部位同时评价它们。将细胞移植后的骨再生与来自对照的基线参数进行比较，以鉴定促进成骨的先导组合。接下来，该项目将确定在巩固阶段加强注射BM-MSCs是否能进一步改善骨再生（目标2）。将初始细胞移植联合加强注射后的骨再生与仅初始细胞移植的骨再生进行比较。使用自体富血小板血浆（PRP）携带BM-MSC用于注射的效果也将通过比较注射中包含PRP的DO部位与不含PRP的DO部位来确定。目标1和2的组合数据将用于创建最佳治疗方案，以在加速DO方案中进行评价，该方案具有更快的牵引和更短的巩固（目标3）。这些研究将确定与没有细胞扩增的常规DO相比，具有自体干细胞干预的优化DO是否可以大幅缩短（数周）DO治疗时间，同时实现相似的骨再生质量和数量。总的来说，该项目有可能建立一个新的范例，用于管理大型颅面骨缺损或骨缺损，使用牵引成骨。