Multifunctional bone putty for craniomaxillofacial bone repair

颅颌面骨修复多功能骨泥

基本信息

批准号：
8666632
负责人：
Ambalangodage Champa Jayasuriya
金额：
$ 37.88万
依托单位：
UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8666632
关键词：
Allografting Autologous Transplantation Benign Biocompatible Biocompatible Materials Biological Assay Biology Biomechanics Blood Vessels Bone Growth Bone Morphogenetic Proteins Bone Regeneration Bone Tissue Bone Transplantation CD34 gene Calcium Chloride Calvaria Cells Chemicals Chitosan Clinical Closed Fractures Collagen Communities Data Defect Development Diagnostic radiologic examination Encapsulated Environment Extracellular Matrix Goals Growth Growth Factor Healed Hematopoietic Histology Immunohistochemistry Implant In Vitro Infiltration Injectable Injection of therapeutic agent Kinetics Lead Measures Mechanics Medical Mesenchymal Methods Methylcellulose Molds Musculoskeletal Diseases Natural regeneration Oils Operative Surgical Procedures Organic solvent product Orthopedics Osteoblasts Osteogenesis Outcome Patients Pharmaceutical Preparations Phenotype Porifera Porosity Process Production Property Public Health Rattus Reconstructive Surgical Procedures Regenerative Medicine Research Sampling Shapes Site Structure Techniques Technology Temperature Testing Time Tissues Transplanted tissue Vascular Endothelial Growth Factors Vascularization Vertebral column Work X-Ray Computed Tomography angiogenesis base biomaterial compatibility bone bone healing bone morphogenetic protein 2 calcium phosphate controlled release cost craniomaxillofacial design efficacy testing healing implantation in vivo innovation minimally invasive novel operation polyclonal antibody public health relevance reconstruction repaired scaffold substantia spongiosa

项目摘要

DESCRIPTION (provided by applicant): Craniomaxillofacial reconstruction continues to be a significant clinical challenge. The estimated cost for repairing craniomaxillofacial defects exceeds several billion dollars. Reconstructive surgery is primarily aimed at restoring the patient to normal function using bone grafts such as autografts, allografts, and synthetic materials. However, currently available treatment methods have significant clinical drawbacks. Therefore, there is an urgent clinical need to create a novel bone graft material that can be used to restore craniomaxillofacial defects successfully and avoids drawbacks of current bone grafts. A unique design criterion is developed to synthesize bone putty to achieve a novel multifunctionality that serves for better repair and/or regeneration of damaged or lost craniomaxillofacial bone tissues. We hypothesize that novel, multifunctional bone putty promotes bone formation at the local defect site. The bone putty will be synthesized using growth factors encapsulated chitosan microparticles, calcium chloride, and methyl cellulose. Each material selected for bone putty provides bone-specific properties to enhance bone growth. The multifunctional properties cannot be achieved with currently available bone graft substitutes. One of the main advantage of this approach compared with traditional block scaffolds, is that this bone putty can be administered by injection, creating the possibility of filling defects of different shapes and size through minimally invasive surgery. Upon implantation, our bone putty is expected to mold easily to the irregular implant site, and the pores should provide a space for both bone tissue and vascular ingrowth, as required for effective healing. Our main goal is to create bone putty that has bone-specific multifunctionality using benign biomaterials and mild processing techniques and that will restore and heal bone defects at local sites. Therefore, this bone putty will possess biocompatibility; biodegradability; injectability; osteoconductivity; osteoinductivity moldability; ability to deliver a precise amount of growth factor over time at the local site; structural (not brittle), and mechanical integrity similar to trabecular bone; ability to release C2+ and over time; immobility at the defect site; less mixing and working time at the operation room; porosity required for cell infiltration, bone formation-remodeling, and vascularization at the defect site. Bone morphogenetic protein, (BMP-2) release kinetics from bone putty will be compared with that of commercially available collagen sponge containing BMP-2 (Medtronic) over time. The bone putty will be assessed for the biocompatibility and rate and extent of osteogenesis toward an osteoblast phenotype and production of mineralized matrix in vitro. The bone putty will be implanted into a rat calvarial critical size defect. The outcomes of the bone regeneration from bone putty will be compared with commercially available calcium phosphate cement or collagen sponge with BMP-2.

描述（由申请人提供）：颅颌面重建仍然是一个重大的临床挑战。修复颅颌面缺损的估计费用超过数十亿美元。重建手术的主要目的是使患者恢复健康使用骨移植物（例如自体移植物、同种异体移植物和合成材料）恢复正常功能。然而，目前可用的治疗方法具有显着的临床缺陷。因此，临床迫切需要研制一种新型骨移植材料，能够成功修复颅颌面缺损，并避免现有骨移植的缺点。开发了一种独特的设计标准来合成骨泥，以实现一种新颖的多功能性，可以更好地修复和/或再生受损或丢失的颅颌面骨组织。我们假设新型多功能骨泥可促进局部缺损部位的骨形成。骨泥将使用生长因子封装的壳聚糖微粒、氯化钙和甲基纤维素合成。骨泥所选择的每种材料都具有骨骼特有的特性，可促进骨骼生长。目前可用的骨移植替代品无法实现多功能特性。与传统块支架相比，这种方法的主要优点之一是这种骨泥可以通过注射给药，从而通过微创手术填充不同形状和大小的缺损成为可能。植入后，我们的骨泥预计会很容易在不规则的植入部位上成型，并且孔应该为骨组织和血管向内生长提供空间，以满足有效愈合的需要。我们的主要目标是使用良性生物材料和温和的加工技术制造具有骨骼特异性多功能性的骨泥，并且能够修复和治愈局部部位的骨缺损。因此，这种骨泥将具有生物相容性；生物降解性；可注射性；骨传导性；骨诱导性、成型性；随着时间的推移，能够在本地站点提供精确数量的生长因子；结构（不易碎）和机械完整性类似于骨小梁；随着时间的推移释放 C2+ 的能力；缺陷部位不动；减少手术室的混合和工作时间；缺损部位细胞浸润、骨形成重塑和血管化所需的孔隙度。骨形态发生蛋白（BMP-2）从骨泥中的释放动力学将与含有 BMP-2（美敦力）的市售胶原蛋白海绵随时间的释放动力学进行比较。将评估骨泥的生物相容性以及成骨细胞表型的成骨速率和程度以及体外矿化基质的产生。骨泥将被植入大鼠颅骨临界尺寸缺损处。骨泥的骨再生结果将与市售磷酸钙水泥或含有 BMP-2 的胶原海绵进行比较。