In Vivo Performance of Osteochondral Allografts

同种异体骨软骨移植物的体内性能

• 批准号: 7526212
• 负责人: WILLIAM D BUGBEE
• 金额: $ 33.99万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7526212
• 关键词: Affect; Allografting; Animal Model; Apoptosis Inhibitor; Apoptotic; Arthritis; Biological; Biological Assay; Bone Marrow; Cartilage; Cartilage injury; Cells; Centrifugation; Cessation of life; Chondrocytes; Clinical; Condition; Conflict (Psychology); Cryopreservation; Culture Media; Defect; Disease; Elements; Equilibrium; Excision; Fostering; Future; Gene Expression; Genus Capra; Goat; Grant; Healed; Health; Human; Hyaline Cartilage; In Vitro; Individual; Injury; Joints; Lactated Ringer' s Solution; Lead; Left; Life Expectancy; Lubrication; Manuals; Methods; Modality; Modeling; Modification; N.I.H. Research Support; Numbers; Operative Surgical Procedures; Orthopedics; Outcome; Patients; Pattern; Performance; Physicians; Population; Property; Prosthesis; Protocols documentation; Public Health; Replacement Arthroplasty; Research; Retrieval; Role; Safety; Scientist; Serum; Surgeon; Techniques; Temperature; Testing; Time; Tissue Banks; Tissue Engineering; Tissue Grafts; Tissues; Translating; Transplantation; Up-Regulation; Week; Weight-Bearing state; articular cartilage; base; clinical application; clinical effect; clinically relevant; concept; day; design; disability; follow-up; healing; implantation; improved; in vivo; injured; innovation; instrument; interest; osteochondral tissue; preference; repaired; response; restoration; survivorship

DESCRIPTION (provided by applicant): In the skeletally mature individual, hyaline articular cartilage does not heal effectively when injured and the natural progression of acquired articular cartilage defects is predictably poor, commonly culminating in joint arthrosis. Physician and patient demands are fueling interest in biological resurfacing and restoration as an alternative to prosthetic joint replacement in an active patient population with an increased life expectancy. Fresh osteochondral allografting currently remains the only treatment option that reliably restores anatomically appropriate, mature hyaline cartilage in weight bearing osteoarticular defects. This transplantation paradigm is associated with unique challenges mostly related to balancing the essential and seemingly conflicting considerations of graft safety with timely patient-donor matching. Maximizing the storage interval of allograft tissue has become a focal topic in tissue banking by extending cold storage times and optimizing storage media. Our recent studies determined that (1) serum-enhanced 4¿C storage media is superior to both modified serum-free storage media and lactated ringer's solution for allograft storage, (2) chondrocyte viability of allografts declines rapidly after 14 days of 4¿C storage in culture media, with (3) the superficial zone of the cartilage appearing preferentially affected, (4) and that these changes are induced in part by upregulation of apoptotic and matrix-related gene expression, and (5) that 37¿C storage media maintains chondrocyte viability for up to 4 weeks. Also (6) impact insertion of osteochondral grafts induces chondrocyte death with a similar pattern of the superficial zone being preferentially affected. While results using traditional fresh allograft protocols have been consistently good even in long-term follow-up, the clinical consequences of prolonged cold storage of articular cartilage on chondrocyte health and overall graft quality remain largely unquantified. Likewise, while mechanisms of cartilage injury sustained during graft insertion have been postulated, their extent and clinical effect on graft performance have not been established in vivo. The objectives of this proposal are to investigate how storage parameters and insertion modality affect chondrocyte viability, and, consequently, the efficacy of osteochondral allografts in vivo by (1) testing innovative modifications to allograft storage method in vitro, and (2) to determine effects of storage and select allograft insertion techniques on graft performance and clinically relevant outcomes in vivo. PUBLIC HEALTH RELEVANCE: The proposed research will foster understanding of the performance of osteochondral allograft transplants in the treatment of cartilage injury and disease. This may lead to improved clinical outcomes in affected individuals, as well as decreased disability associated with joint injuries and subsequent arthritis.

描述（由适用提供）：在骨骼成熟的个体中，透明关节软骨在受伤时无法有效地健康，并且获得的关节软骨缺陷的自然进展可预测，通常很差，通常在关节性关节中最终导致。医师和患者的需求激发了人们对生物学重塑和恢复的兴趣，作为在预期寿命增加的活跃患者人群中替代假肢关节替代的一种替代品。目前，新鲜的骨软骨分配仍然是唯一可靠地恢复解剖学上适当的成熟透明软骨的治疗选择。这种移植范例与与及时的患者匹配的基本且看似相互矛盾的考虑有关，主要与平衡基本且看似相互矛盾的考虑有关的独特挑战有关。通过延长冷藏时间并优化存储介质，最大化分类组织的存储间隔已成为组织库的焦点主题。 Our recent studies determined that (1) serum-enhanced 4¿ C storage media is superior to both modified serum-free storage media and lactated ringer's solution for allocraft storage, (2) chondrocyte viability of allocrafts declines rapidly after 14 days of 4¿ C storage in culture media, with (3) the superficial zone of the cartilage appearing preferentially affected, (4) and that these changes are induced in part by upregulation of凋亡和基质相关的基因表达，（5）37？c储存培养基可保持软骨细胞活力长达4周。 （6）骨软骨移植物的影响插入会诱导软骨细胞死亡，而表面区域的类似模式更可能影响。尽管使用传统新鲜同种异体方案的结果即使在长期随访中也一直很好，但长期冷藏关节软骨对软骨细胞健康和整体移植物质的临床后果仍然在很大程度上没有量化。同样，尽管已经发布了在移植物插入过程中持续的软骨损伤机制，但在体内尚未确定其对移植性能的程度和临床影响。 The objectives of this proposal are to investigate how storage parameters and insertion modality affect chondrocyte viability, and, consequently, the effectiveness of osteochondral allographies in vivo by (1) testing innovative modifications to allograph storage method in vitro, and (2) to determine effects of storage and select allograft insertion techniques on grain performance and clinically relevant outcomes in vivo. 公共卫生相关性：拟议的研究将促进对软骨损伤和疾病治疗中骨软骨移植移植的性能的理解。这可能会导致受影响个体的临床结果改善，并改善与关节损伤和随后的关节炎相关的残疾。