Bone Regeneration Via Silk Biomaterials

通过丝生物材料进行骨再生

• 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
• 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

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、疾病或先天性畸形引起的严重骨缺损，仍然是骨科医学中具有挑战性的问题。由于所采用的临床修复模式导致的原生骨组织再生速度慢、第二部位发病率高、机械稳定性差以及与周围组织缺乏整合，目前恢复此类骨缺损完整功能的选择受到限制。为了克服目前的限制，需要新的选择来加快新骨形成的速度和程度，以及与周围组织的整合。在这个竞争性更新应用中，一种新的丝蛋白基质将通过生物工程来优化这些目标，以实现大缺陷骨再生。拟议的研究建立在当前资助的结果基础上，该结果证明了丝素蛋白3D多孔基质在体外和体内骨再生中的独特和有用的属性。在我们提出的研究中，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陷整合的速度和程度，并结合生物工程肽粘合剂来促进与相邻母骨的相互作用。这些增强的，可降解的和

项目成果

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

基于干细胞和脚手架的组织工程方法，用于骨软骨再生医学。

• 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

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

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.

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

Aligned silk-based 3-D architectures for contact guidance in tissue engineering.

• DOI: 10.1016/j.actbio.2011.12.015
• 发表时间: 2012-04
• 期刊: ACTA BIOMATERIALIA
• 影响因子: 9.7
• 作者: Oliveira, A. L.;Sun, L.;Kim, H. J.;Hu, X.;Rice, W.;Kluge, J.;Reis, R. L.;Kaplan, D. L.
• 通讯作者: Kaplan, D. L.