Injectable Anabolic Biomaterials for Bone Regeneration

用于骨再生的可注射合成代谢生物材料

• 批准号: 8487370
• 负责人: Lakshmi S Nair
• 金额: $ 7.14万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8487370
• 关键词: AKT Signaling Pathway; Address; Adopted; Alkaline Phosphatase; Animal Model; Apoptosis; Apoptotic; Biocompatible Materials; Biological; Biomechanics; Bone Marrow; Bone Marrow Transplantation; Bone Regeneration; Calcium; Calvaria; Cell Culture Techniques; Cell Death; Cell Differentiation process; Cell Proliferation; Cell Survival; Cell Therapy; Cell Transplantation; Cell Transplants; Cell physiology; Cells; Characteristics; Clinical; Clinical Trials; Complex; Defect; Deposition; Development; Disease; Encapsulated; Engineering; Evaluation; Face; Family; Gel; Gelatin; Glycoproteins; Goals; Healed; Histological Techniques; Human; Imaging Techniques; In Vitro; Inflammatory; Injectable; Injury; Iron; Iron-Binding Proteins; Laboratories; Lactoferrin; Light; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Modeling; Musculoskeletal; Natural regeneration; Organ; Osteoblasts; Osteocalcin; Osteogenesis; Performance; Phenotype; Pilot Projects; Property; Rattus; Recombinants; Research; Serum; Site; Source; Staging; Stem cells; Technology; Testing; Therapeutic; Tissue Engineering; Tissues; Transferrin; Translations; Transplantation; Vascularization; base; body system; bone; design; healing; improved; in vivo; in vivo Model; injured; insight; member; osteoblast differentiation; osteogenic; osteogenic protein; osteopontin; prevent; regenerative; repository; response; self-renewal; skeletal; skeletal regeneration; stem; success; tissue regeneration; wound

DESCRIPTION (provided by applicant): PROJECT SUMMARY Cell transplantation is emerging as a promising clinical strategy to accelerate tissue regeneration. However, the successful clinical translation of this technology faces several engineering and biological challenges. Major challenges lies in our inability to deliver and retain the transplanted cells at the healing site and prevent the uncontrolled cell death in the unfriendly milieu of the injured tissue. The long-range goal of our laboratory is to regenerate complex tissues, organs and organ systems using the principles of regenerative engineering with advanced biomaterials and unique cell sources. One of our immediate objectives is to design cell delivery vehicles that will transiently act as a favorable microenvironment at the healing site to modulate cell performance upon transplantation. The aim of the proposed study is to evaluate the efficacy of an injectable biomaterial based on lactoferrin as an artificial microenvironment to increase the survival and osteogenic activity of encapsulated rat mesenchymal stem cells (rBMSC). The proposed research is designed based on our preliminary studies demonstrating the anti-apoptotic, mitogenic and osteogenic effect of soluble recombinant human lactoferrin (rhLf). The hypothesis being tested is that the injectable recombinant human lactoferrin gel (rhLfG) will present a favorable osteostimulative microenvironment by inhibiting cellular apoptosis and promoting cell proliferation and osteogenic differentiation. The experimental plan will explore the bioactivity of the injectable recombinant human lactoferrin gel based cell delivery vehicle through two specific aims. The first aim is designed to evaluate in vitro the anti apoptotic, mitogenic and osteogenic effect of recombinant human lactoferrin gels (rhLfG) to rat bone marrow derived mesenchymal stem cells. Cell culture conditions that are known to induce cellular apoptosis will be used. An injectable gelatin gel will be used as a control matrix to evaluate the efficacy of lactoferrin gel microenvironment in improving cell survival and promoting cell proliferation and differentiation. The second aim is designed to evaluate in vivo the efficacy of the injectable rhLfG in enhancing rBMSC survival, proliferation and osteogenesis, using a rat calvarial bone defect model. We hypothesize that the biologically active microenvironment provided by rhLfG will promote bone regeneration and better host tissue integration upon rBMSC delivery compared to injectable gelatin delivery vehicle. The proposed pilot study will help to understand the feasibility of developing a cell instructive injectable regenerative biomaterial based on rhLf as a cell delivery vehicle for bone regeneration. If successful, the injectable lactoferrin based delivery vehicle could have a significant impact in the clinical translation of cell based therapeutic strategies by addressing some of its current limitations.

描述（由申请人提供）：项目摘要细胞移植正在成为加速组织再生的一种有希望的临床策略。但是，这项技术的成功临床翻译面临着几种工程和生物学挑战。主要挑战在于我们无法在愈合部位传递和保留移植细胞，并防止受伤组织不友好的环境中不受控制的细胞死亡。我们实验室的远距离目标是使用带有先进的生物材料和独特细胞来源的再生工程原理再生复杂的组织，器官和器官系统。我们的直接目标之一是设计电池输送车辆，该车辆将在愈合部位瞬时充当有利的微环境，以调节移植后的细胞性能。拟议研究的目的是评估基于乳铁蛋白作为人工微环境的可注射生物材料的功效，以增加封装大鼠间充质干细胞（RBMSC）的生存和成骨活性。拟议的研究是基于我们的初步研究设计的，该研究表明可溶性重组人乳铁蛋白（RHLF）的抗凋亡，有丝分裂和成骨作用。被检验的假设是，可注射的重组人乳铁蛋白凝胶（RHLFG）将通过抑制细胞凋亡并促进细胞增殖和成骨分化来提出有利的骨刺激性微环境。实验计划将探讨 通过两个特定目标，可注射的重组人乳铁蛋白凝胶的细胞递送车辆。第一个目的旨在在体外评估重组人乳铁蛋白凝胶（RHLFG）对大鼠骨髓衍生的间充质干细胞的抗凋亡，有丝分裂和成骨作用。将使用已知会诱导细胞凋亡的细胞培养条件。可注射的明胶凝胶将用作评估乳铁蛋白凝胶功效的对照基质 在改善细胞存活和促进细胞增殖和分化方面的微环境。第二个目的旨在在体内使用大鼠钙质骨缺陷模型评估可注射rhlfg在增强RBMSC存活，增殖和成骨的功效。我们假设RHLFG提供的生物活性微环境将在RBMSC递送后促进骨骼再生和更好的宿主组织整合，而与可注射的明胶递送车相比。拟议的试点研究将有助于理解基于RHLF作为骨再生的细胞输送工具开发细胞指导性注射性再生生物材料的可行性。如果成功，则可注射乳铁蛋白的递送工具可能会对基于细胞的治疗策略的临床翻译产生重大影响 解决其当前局限性。