Bone Regeneration Via Silk Biomaterials

通过丝生物材料进行骨再生

基本信息

批准号：
7877754
负责人：
DAVID L. KAPLAN
金额：
$ 30.15万
依托单位：
TUFTS UNIVERSITY MEDFORD
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-13 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7877754
关键词：
Acceleration Address Adhesions Adhesives Adsorption Allogenic Allografting Anesthetics Animal Model Animals Area Autologous Autologous Transplantation Binding Biocompatible Biocompatible Materials Biological Biology Biomechanics Biomedical Engineering Biomimetics Blood Vessels Bombyx Bombyx mori Bone Banks Bone Density Bone Growth Bone Morphogenetic Proteins Bone Regeneration Bone Tissue Bone Transplantation Canis familiaris Cell Adhesion Cell Therapy Cells Cellular biology Ceramics Characteristics Chemicals Chimeric Proteins Clinical Clinical Trials Collaborations Collagen Complex Congenital Abnormality Coupling Defect Deformity Development Disease Engineering Environment Equus caballus Escherichia coli Excision Faculty Failure Family suidae Femur Fibrin Tissue Adhesive Fibroins Fracture Genetic Engineering Goals Goat Graft Rejection Grant Growth Factor Habilitation Harvest Head Healed Hemorrhage Human Human Resources Hydroxyapatites Image Immune Implant In Vitro Infection Injury Institutes Laboratory Research Lead Mechanics Mediating Medicine Mesenchymal Stem Cells Minerals Modeling Molecular Biology Morbidity - disease rate Morus Mus Musculoskeletal Natural regeneration North America Nude Rats Operative Surgical Procedures Orthopedics Oryctolagus cuniculus Osteoblasts Osteogenesis Outcome Outcome Assessment Outcome Measure Outcome Study Pain Parents Patients Peptides Physiological Polymers Porosity Postoperative Period Predisposition Process Property Protein Family Proteins Rattus Recombinants Recording of previous events Research Research Personnel Risk Schools Sheep Silk Site Surface Surgical sutures System Techniques Technology Temperature Tertiary Protein Structure Testing Time Tissue Engineering Tissues Trauma United States National Institutes of Health Vascular Endothelial Growth Factors Vascularization Vesicle Veterinary Medicine Xenograft procedure aqueous base biomaterial compatibility bone bone morphogenetic protein 2 bone quality clinical application controlled release density dentin matrix protein 1 design experience flexibility gene therapy hazard healing improved in vivo insight interfacial long bone meetings molecular recognition morphogens novel novel strategies osteogenic professor repaired restoration rib bone structure scaffold skeletal stem cell biology success tissue regeneration transmission process tumor von Willebrand Factor wound

项目摘要

DESCRIPTION (provided by applicant): Critical sized bone defects caused by injury, disease or congenital malformations, remain a challenging problem in orthopedic medicine. Current options to restore full function to such bone defects are limited due to slow rates of regeneration of native bone tissue, second site morbidity, poor mechanical stability and lack of integration with surrounding tissues depending on the mode of clinical repair utilized. New options to accelerate the rate and extent of new bone formation, as well as integration to surrounding tissues are needed to overcome current limitations. In this competitive renewal application, a novel silk protein matrix will be bioengineered to optimize these goals to achieve large defect bone regeneration. The proposed studies build off of the results from the current grant that demonstrated the unique and useful attributes of a silk fibroin protein 3D porous matrix for in vitro and in vivo bone regeneration. In the proposed research, our goal is to accelerate the rate and extent of bone formation and integration across the defect through the combined delivery of BMP-2 and VEGF in the 3D protein matrices, and to incorporate bioengineered peptide adhesives to promote interactions with adjacent parent bone. These enhanced, degradable and biocompatible 3D porous silk matrices functionalized with growth factors and adhesion capabilities will be studied in a rat critical sized femur defect model to optimize their design. Subsequent to optimization, in the final aim of the study, the implants will be assessed in a critical-size goat femur defect model. Our goal is to conclude the study with an optimized design for these new 3D porous protein matrices in order to pursue human clinical trials. Outcome assessments for the three aims will be based on mineral density, homogeneity of mineral distribution and mechanical integrity of the repairs in the small and then large animal critical sized defects. To achieve the goals, an interdisciplinary team of investigators has been assembled to address the challenges with expertise in biomaterial matrix design, stem cell biology, biomechanics, imaging and veterinary medicine.

描述（由申请人提供）：由损伤、疾病或先天畸形引起的临界大小的骨缺损仍然是骨科医学中的一个具有挑战性的问题。由于天然骨组织再生速度慢、第二部位发病率、机械稳定性差以及缺乏与周围组织的整合（取决于所使用的临床修复模式），目前恢复此类骨缺损全部功能的选择受到限制。需要新的选择来加速新骨形成的速度和范围，以及与周围组织的整合，以克服当前的限制。在这一竞争性更新应用中，将通过生物工程设计一种新型丝蛋白基质来优化这些目标，从而实现大缺损骨再生。拟议的研究以当前资助的结果为基础，该资助证明了丝素蛋白 3D 多孔基质对于体外和体内骨再生的独特和有用的属性。在拟议的研究中，我们的目标是通过在 3D 蛋白基质中联合递送 BMP-2 和 VEGF 来加速骨形成和跨缺损整合的速度和程度，并结合生物工程肽粘合剂以促进与相邻亲本的相互作用骨。这些增强的、可降解的和将在大鼠临界尺寸股骨缺陷模型中研究具有生长因子和粘附能力的生物相容性 3D 多孔丝基质，以优化其设计。在优化之后，为了研究的最终目标，将在临界尺寸山羊股骨缺陷模型中对植入物进行评估。我们的目标是通过对这些新型 3D 多孔蛋白质基质的优化设计来结束研究，以便进行人体临床试验。这三个目标的结果评估将基于矿物密度、矿物分布的均匀性以及小型和大型动物临界尺寸缺陷修复的机械完整性。为了实现这些目标，我们组建了一个跨学科的研究团队，利用生物材料基质设计、干细胞生物学、生物力学、成像和兽医学方面的专业知识来应对挑战。

项目成果

期刊论文数量（60）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Stem cell- and scaffold-based tissue engineering approaches to osteochondral regenerative medicine.

DOI：
10.1016/j.semcdb.2009.03.017
发表时间：
2009-08
期刊：
Seminars in cell & developmental biology
影响因子：
7.3
作者：
Sundelacruz S;Kaplan DL
通讯作者：
Kaplan DL

Relationships between degradability of silk scaffolds and osteogenesis.

DOI：
10.1016/j.biomaterials.2010.04.028
发表时间：
2010-08
期刊：
BIOMATERIALS
影响因子：
14
作者：
Park, Sang-Hyug;Gil, Eun Seok;Shi, Hai;Kim, Hyeon Joo;Lee, Kyongbum;Kaplan, David L.
通讯作者：
Kaplan, David L.

Review physical and chemical aspects of stabilization of compounds in silk.

DOI：
10.1002/bip.22026
发表时间：
2012-06
期刊：
Biopolymers
影响因子：
2.9
作者：
Pritchard EM;Dennis PB;Omenetto F;Naik RR;Kaplan DL
通讯作者：
Kaplan DL

The use of injectable sonication-induced silk hydrogel for VEGF(165) and BMP-2 delivery for elevation of the maxillary sinus floor.

DOI：
10.1016/j.biomaterials.2011.08.047
发表时间：
2011-12
期刊：
BIOMATERIALS
影响因子：
14
作者：
Zhang, Wenjie;Wang, Xiuli;Wang, Shaoyi;Zhao, Jun;Xu, Lianyi;Zhu, Chao;Zeng, Deliang;Chen, Jake;Zhang, Zhiyuan;Kaplan, David L.;Jiang, Xinquan
通讯作者：
Jiang, Xinquan

Nucleation and growth of mineralized bone matrix on silk-hydroxyapatite composite scaffolds.

DOI：
10.1016/j.biomaterials.2010.12.058
发表时间：
2011-04
期刊：
BIOMATERIALS
影响因子：
14
作者：
Bhumiratana, Sarindr;Grayson, Warren L.;Castaneda, Andrea;Rockwood, Danielle N.;Gil, Eun S.;Kaplan, David L.;Vunjak-Novakovic, Gordana
通讯作者：
Vunjak-Novakovic, Gordana