Development of a Multi-phased Scaffold for Soft Tissue to Bone Integration

软组织骨整合多相支架的开发

• 批准号: 7140665
• 负责人: HELEN H LU
• 金额: $ 15.51万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-22 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140665
• 关键词: animal tissue; bioengineering /biomedical engineering; biomaterial interface interaction; biomimetics; calcium phosphate; cell cell interaction; fibroblasts; infrared spectrometry; interferometry; knee; ligaments; mixed tissue /cell culture; musculoskeletal injury; musculoskeletal regeneration; musculoskeletal transplantation; normal ossification; orthopedics; osteoblasts; polymerase chain reaction; scanning electron microscopy; tissue engineering; tissue support frame

DESCRIPTION (provided by applicant): The anterior cruciate ligament (ACL) is the most frequently injured knee ligament, with approximately 75,000 ligament surgeries performed annually in the United States. The autologous bone-patellar tendon- bone graft and the hamstring tendon graft are the most commonly utilized grafts for ACL reconstruction surgeries. In the early post-operative healing period, the site of graft contact in the bone tunnels represents the weakest point mechanically. Therefore, the clinical success of ACL reconstructive surgeries depends on graft fixation and the formation of a functional interface between bone and soft tissue. The native ACL-bone insertion zone is comprised of four different regions: ligament, non-mineralized fibrocartilage, mineralized fibrocartilage, and bone. Our approach to engineering a functional interface is through the novel co-culture of osteoblasts and ligament fibroblasts on a multi-phased scaffold system with a gradient of structural and functional properties that mimic those of the native insertion zones. These design parameters are chosen because multiple types of cells and an inherent increase in mineral content are both observed across the insertion zone. Our hypothesis is that the co-culture of osteoblasts and ligament fibroblasts on a multi-phased scaffold with a biomimetic calcium phosphate (Ca-P) composition will result in the formation of a fibrocartilage-like interracial zone in the scaffold. To test this hypothesis, the specific aims of this proposal are: Aim 1. To characterize the mineral content (Ca-P distribution, Ca/P ratio) across the native ACL-bone interface. Aim 2. To develop a multi-phased scaffold with a biomimetic compositional variation of Ca-P and to examine the effects of osteoblast-ligament fibroblast co-culture on the development of interfacial zone specific markers (proteoglycan, types II & X collagen) on this scaffold. The global hypothesis of our approach is that the compositional and structural distributions in the native tissue are correlated with functionality. The proposed evaluation of the ACL-bone interface will provide previously unavailable insight into the organizational characteristics at the insertion zone, and identify design objectives for scaffolds with controlled inhomogeneity. By implementing both osteoblast- fibroblast co-culture and the appropriate zonal dependent variations in mineral content into the design of multi-phased scaffolds, we seek to lay the foundation for the development of functional biomimetic scaffolds which can promote healing and facilitate soft tissue graft and bone integration in vivo.

描述（由申请人提供）：前交叉韧带（ACL）是最常见的膝盖韧带，每年在美国进行约75,000张韧带手术。自体骨肌腱骨移植和腿筋肌腱移植是ACL重建手术最常用的移植物。在术后早期愈合期间，骨隧道中的移植接触部位在机械上代表了最弱点。因此，ACL重建手术的临床成功取决于移植物的固定以及骨骼和软组织之间功能界面的形成。 天然ACL骨插入区由四个不同的区域组成：韧带，非矿化纤维球杆菌，矿化纤维球橄榄球和骨骼。我们的工程界面方法是通过在多型支架系统上具有成骨细胞和韧带成纤维细胞的新型共培养，具有模仿天然插入区域的结构和功能性能的梯度。选择这些设计参数是因为在整个插入区域都观察到多种类型的细胞和矿物含量的固有增加。我们的假设是，成骨细胞和韧带成纤维细胞的共培养在多型脚手架上，磷酸钙（CA-P）成分（CA-P）成分将导致在脚手架中形成纤维球杆菌样的异地区。为了检验这一假设，该提案的具体目的是： 目的1。表征跨天然ACL骨界面上的矿物含量（CA-P分布，CA/P比）。 目的2。开发具有CA-P的仿生成分变化的多型支架，并检查成骨细胞韧带成纤维细胞共培养对界面区特异性标记（Proteoglycan，proteoglycan，型II型和X胶原）的影响。 我们方法的全球假设是，天然组织中的组成和结构分布与功能相关。对ACL骨接口的拟议评估将提供以前无法获得插入区组织特征的洞察力，并确定具有控制不均匀性的脚手架的设计目标。通过将成骨细胞成纤维细胞共培养和适当的矿物含量依赖性变化实施到基于多型支架的设计中，我们试图为开发功能性仿生型支架的发展奠定基础，这些脚手架可以促进愈合并促进软组织移植物和骨骼整合体内的Vivo。

项目成果

Orthopedic interface tissue engineering for the biological fixation of soft tissue grafts.

• DOI: 10.1016/j.csm.2008.08.006
• 发表时间: 2009-01
• 期刊: CLINICS IN SPORTS MEDICINE
• 影响因子: 2
• 作者: Moffat, Kristen L.;Wang, I-Ning Elaine;Rodeo, Scott A.;Lu, Helen H.
• 通讯作者: Lu, Helen H.

Role of cell-cell interactions on the regeneration of soft tissue-to-bone interface.

细胞间相互作用对软组织与骨界面再生的作用。

• DOI: 10.1109/iembs.2006.259456
• 发表时间: 2006
• 期刊: Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference
• 作者: Wang,I-NingE;Lu,HelenH
• 通讯作者: Lu,HelenH

In vivo evaluation of a tri-phasic composite scaffold for anterior cruciate ligament-to-bone integration.

用于前十字韧带骨整合的三相复合支架的体内评估。

• DOI: 10.1109/iembs.2006.259296
• 发表时间: 2006
• 期刊: Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference
• 作者: Spalazzi,JeffreyP;Dagher,Elias;Doty,StephenB;Guo,XEdward;Rodeo,ScottA;Lu,HelenH
• 通讯作者: Lu,HelenH

Cellular interactions regulate stem cell differentiation in tri-culture.

• DOI: 10.1080/03008207.2016.1230106
• 发表时间: 2016-11
• 期刊: Connective tissue research
• 影响因子: 2.9
• 作者: Wang IE;Bogdanowicz DR;Mitroo S;Shan J;Kala S;Lu HH
• 通讯作者: Lu HH

Biomimetic scaffold design for functional and integrative tendon repair.

• DOI: 10.1016/j.jse.2011.11.016
• 发表时间: 2012-02
• 期刊: JOURNAL OF SHOULDER AND ELBOW SURGERY
• 影响因子: 3
• 作者: Zhang, Xinzhi;Bogdanowicz, Danielle;Erisken, Cevat;Lee, Nancy M.;Lu, Helen H.
• 通讯作者: Lu, Helen H.