Tunable Nanolayer-Polymer Composite Patches for Cell-Free CMF Repair

用于无细胞 CMF 修复的可调节纳米层-聚合物复合贴片

• 批准号: 9762080
• 负责人: Paula T Hammond
• 金额: $ 54.01万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762080
• 关键词: Accidents; Address; Angiogenic Factor; Area; Behavior; Birth trauma; Blood Vessels; Bolus Infusion; Bone Marrow; Bone Regeneration; Bone Resorption; Bone Tissue; Bone Transplantation; Calvaria; Cell Differentiation process; Cell Proliferation; Cell-Free System; Cells; Cephalic; Characteristics; Child; Childhood; Clinic; Congenital Abnormality; DNA; Defect; Deformity; Development; Dimensions; Dose; Electrostatics; Evaluation; Face; Film; Formulation; Generations; Gold; Growth; Growth Factor; Harvest; Head and Neck Cancer; Health; Hybrids; Hydrogels; Implant; In Vitro; Jaw; Lead; Lesion; Mandible; Maxilla; Membrane; Minerals; Modeling; Morbidity - disease rate; Natural regeneration; Operative Surgical Procedures; Oryctolagus cuniculus; Osteogenesis; Outcome; Pain; Pathologic; Patients; Physiological; Plasmids; Platelet-Derived Growth Factor; Polymers; Pre-Clinical Model; Procedures; Production; Proteins; Rattus; Recovery; Risk; Shapes; Site; Stem cells; Structure; Surface; System; Technology; Testing; Thinness; Time; Tissues; Transfection; Trauma; Traumatic injury; Vascular Endothelial Growth Factors; Vascularization; Work; Wound Healing; angiogenesis; appropriate dose; assault; base; biodegradable polymer; bone; bone morphogenetic protein 2; calcium phosphate; clinically relevant; craniofacial; craniomaxillofacial; cranium; design; face bone structure; flexibility; functional disability; healing; implantation; in vivo; interest; mechanical properties; nanoscale; nucleic acid delivery; osteoinductive factor; precursor cell; public health relevance; reconstruction; recruit; release factor; repaired; restoration; scaffold; side effect; stem; tissue regeneration; tissue repair

 DESCRIPTION (provided by applicant): The impact of large cranial and facial bone defects from birth defects or trauma can result in devastating functional impairment and physical changes, yet craniomaxillofacial (CMF) reconstruction is one of the most challenging areas for bone regeneration. It requires modulated repair that leads to bone tissue regeneration while maintaining or recapitulating facial structure and enabling adaptive growth remodeling in pediatric cases. Current approaches rely on the use of patient or donor bone and present issues of insufficient bone availability, morbidity at the bone donor site, or incompatibility of donated bone. The ability to gain healthy, highly vascularized and well developed bone tissue over reasonable timeframes remains limited. New synthetic or hybrid materials designed for bone regeneration often lack either the mechanical properties or conformability to shape new tissue to the contours of the face, or the ability to controllably release bioactive agents at rates that hel generate new bone tissue. The release of growth factors that regulate the differentiation of the patient's native stem cells to bone, and enable vascularization of the bone tissue offers great potential for this area, but most existing systems act as depots that release the proteins with a large bolus and need unusually high loadings. The result is a greatly lowered efficacy due to clearance of much of the protein from the local region of interest, and the risk of undesired side effects from large systemic exposure of the factors. In this work, we seek to release these potent bioactive agents in physiologically appropriate dose levels from degradable scaffolds to recruit native bone precursor cells to the healing site, and achieve full integration of new and native bone. This approach does not require the co-implantation of stem cells from the patient or a donor, which can require painful and expensive bone marrow extraction and relies on the health, availability and/or compatibility of the patient or donor. In the proposed work, we use a modular cell-free system that isolates the properties of the mechanical scaffold from the bioactive release system. Nanoscale electrostatic layers carrying active growth factors that elute over readily adapted time scales to recapitulate the wound healing cascade and induce rapid bone repair are used to coat a porous degradable polymer membrane. The rigidity or flexibility of the scaffold can be adapted through the choice of underlying polymer substrate. Growth factors and active agents are eluted from the nanolayered coating, which is thin, well- adhered and highly conformal to the features of the substrate. Because release from these systems is slow but sustained, clearance is limited and small amounts of growth factor can be used to induce significant increases in bone formation. The system is modular, enabling the incorporation of single or dual growth factors introduced with different release characteristics, such as an angiogenic factor followed by an osteoinductive factor. We investigate the potential of this approach and evaluate it with a rat mandibular defect model as a tunable, off-the-shelf, cell-free option for craniomaxillofacial bone tissue repair and restoration.

 描述（由申请人提供）：出生缺陷或创伤带来的大颅骨和面部骨骼缺陷的影响会导致毁灭性的功能障碍和身体变化，但是颅颌面（CMF）重建是最具挑战性的骨骼再生区域之一调制修复组织再生，同时维持或回资的构态并实现适应性生长重塑蛋白疾病的疾病。被命中的新合成或杂种材料缺乏机械性能或塑造tisue o tisue o的能力，或者可以控制释放生物活性的能力，使患者的天然干细胞之间的区分。骨头，但大多数出现的系统作为用大量注销的仓库，需要需要需要需求需要需要新的载荷。在这项工作中，大量全身性暴露的副作用的风险。新的和本地的骨骼。从生物活性释放系统中。因素和活性药物从纳米层涂层中洗脱，这是薄的，良好的且高度与基板的特征相吻合的。具有不同的释放特征，例如血管生成因子，然后是骨诱导因子，并用大鼠下颌缺陷模型作为可调的，无细胞的无细胞选择，用于颅面骨组织骨组织修复和恢复。