Multifunctional bone putty for craniomaxillofacial bone repair

颅颌面骨修复多功能骨泥

• 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
• 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

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。修复颅颌面缺陷的估计成本超过数十亿美元。重建手术主要旨在恢复患者 使用骨移植物，例如自体移植，同种异体移植物和合成材料达到正常功能。但是，目前可用的治疗方法具有明显的临床缺点。因此，紧急临床需要创建一种新型的骨移植物材料，该材料可用于成功恢复颅面上的缺陷，并避免当前骨移植物的缺点。 开发了一个独特的设计标准，可以合成骨腻子，以实现一种新型的多功能性，该功能可更好地修复和/或再生受损或失去的颅面骨膜骨组织。我们假设这种新型的多功能骨腻子在局部缺陷部位促进了骨形成。将使用封装的壳聚糖微粒，氯化钙和甲基纤维素合成骨头果皮。选择用于骨头腻子的每种材料都提供骨特异性的特性，以增强骨骼的生长。当前可用的骨移植替代物无法实现多功能性能。与传统的块脚手架相比，这种方法的主要优点之一是，可以通过注射来施用该骨头腻子，从而通过微创手术来填充不同形状和大小的缺陷。植入后，我们的骨灰科预计将很容易塑造到不规则的植入物部位，并且孔应为有效的愈合所需的骨骼组织和血管内生长提供空间。我们的主要目的是创建使用良性生物材料和轻度加工技术具有骨特异性多功能性的骨腻子，并将在当地部位恢复和治愈骨骼缺陷。因此，该骨灰条将具有生物相容性。生物降解性；注射性；骨导率；骨诱导的可可性可；能够在当地地点随着时间的推移提供精确的生长因子；结构（不是脆性），机械完整性类似于小梁骨；能够释放C2+并随着时间的推移；缺陷部位不动；在操作室减少混合和工作时间；细胞浸润，骨骼形成 - 复制和血管化所需的孔隙率。将骨形态发生蛋白（BMP-2）与含有BMP-2（Medtronic）的市售胶原蛋白海绵的骨骼释放动力学释放。将评估骨头的生物相容性，成骨的生物相容性，速率和程度，并在体外评估成骨细胞表型和矿化基质的产生。骨头腻子将被植入大鼠颅骨临界尺寸缺陷中。将骨腻子骨再生的结果与磷酸钙水泥或带有BMP-2的胶原蛋白海绵进行比较。