Tissue Engineering of the Anterior Cruciate Ligament on Resorbable Embroidered Scaffolds: Design of a Hybrid Scaffold Structure Composed of a Biomechanical Unit , a Bio-Functional Unit and a Vital Unit

可吸收刺绣支架上前十字韧带的组织工程：由生物力学单元、生物功能单元和生命单元组成的混合支架结构的设计

• 批准号: 352112919
• 负责人: Dr.-Ing. Annette Breier
• 金额: --
• 依托单位: Leibniz-Institut für Polymerforschung Dresden (IPF)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/352112919?language=en
• 关键词: Tissue; Engineering; Anterior; Cruciate; Ligament

The replacement of the anterior cruciate ligament (ACL) by a tissue engineering approach could be the favored surgical practice in future superseding the transplantation of autologous tendons with limited availability. An essential requirement for the application is a sufficient biomechanical resistance of the surrogate structure. The proposed project focusses on the design of a hybrid scaffold structure capable for ACL tissue engineering. The hybrid structure is composed of a biomechanical unit for the compensation of forces, a bio-functional unit to support an enhanced bio-integration and a vital unit including tissue-specific cells of the mid-substance and enthesis to accelerate tissue regeneration. The approach is based on the tailored triphasic scaffold structure, subsequent functionalization and cell seeding strategies already established in the parent project.To complement the embroidered scaffolds, further functional units such as cell barriers or control structures are included requiring technological advancement, adaption and optimization of the embroidery process along with the applied materials. Bio-integration could be enhanced by a novel method of fluorinating the surface of the synthetic polymer in a gaseous phase as well as by infiltrating collagen preparations into the textile structure. The collagen preparations are processed to stable foams performing an interconnected and aligned pore system inside the textile structure. A scientific question addressed here is the enhanced cell adherence on the fluorinated surfaces of the synthetic polymers. The novel hybrid structures will be seeded with small spheroids prepared by the hanging-drop method already established in the parent project. The hybrid structures seeded with different cell types will be mechanically stimulated and an optimized protocol will be established to the benefit of all cell types of ACL enthesis and mid-substance. Co-cultivation with osteogen and chondrogen differentiated as well as ligament cells will be performed in vitro. Additionally, the positive effect of a cell barrier on the prevention of cell migration and the formation of an enthesis will be studied. An optimized procedure will be chosen and evaluated for ligamentogenesis in a dynamic nude mice model as well as in an orthotopic rabbit ACL reconstruction model.At the end of the project a procedure, comprising the manufacturing of the biomechanical, the bio-functional and the bio-integrative units as well as the cell seeding and cultivation strategies, will be determined directly applicable for a subsequent large animal testing.

通过组织工程方法替代前交叉韧带（ACL）可能是未来替代可用性有限的自体肌腱移植的首选手术实践。应用的基本要求是替代结构具有足够的生物力学抗性。该项目的重点是设计一种能够用于ACL组织工程的混合支架结构。混合结构由用于力补偿的生物力学单元、用于支持增强的生物整合的生物功能单元和包括中间物质和附着点的组织特异性细胞以加速组织再生的生命单元组成。该方法基于母项目中已经建立的定制三相支架结构、后续功能化和细胞接种策略。为了补充刺绣支架，还包括其他功能单元，如细胞屏障或控制结构，这些功能单元需要技术进步，适应和优化刺绣工艺沿着应用材料。可以通过在气相中对合成聚合物表面进行氟化的新方法以及将胶原蛋白制剂渗透到纺织结构中来增强生物整合。将胶原蛋白制剂加工成稳定的泡沫，在纺织品结构内形成互连和对齐的孔隙系统。这里解决的一个科学问题是合成聚合物的氟化表面上的增强的细胞粘附。新的混合结构将播种小球体制备的悬滴方法已经建立在母项目。将对接种有不同细胞类型的混合结构进行机械刺激，并将建立优化方案，以使ACL附着点和中间物质的所有细胞类型受益。将在体外与分化的成骨细胞和软骨细胞以及韧带细胞进行共培养。此外，将研究细胞屏障对防止细胞迁移和附着点形成的积极作用。将选择并评估一种优化的程序，用于动态裸鼠模型以及原位兔ACL重建模型中的韧带生成。在项目结束时，将确定一种程序，包括生物力学、生物功能和生物整合单元的制造以及细胞接种和培养策略，直接适用于随后的大型动物试验。

项目成果

Enhanced Growth of Lapine Anterior Cruciate Ligament-Derived Fibroblasts on Scaffolds Embroidered from Poly(L-lactide-co-ε-caprolactone) and Polylactic Acid Threads Functionalized by Fluorination and Hexamethylene Diisocyanate Cross-Linked Collagen Foams

• DOI: 10.3390/ijms21031132
• 发表时间: 2020-02-01
• 期刊: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• 影响因子: 5.6
• 作者: Goegele, Clemens;Hahn, Judith;Schulze-Tanzil, Gundula
• 通讯作者: Schulze-Tanzil, Gundula

Gas-Phase Fluorination on PLA Improves Cell Adhesion and Spreading

• DOI: 10.1021/acsomega.0c00126
• 发表时间: 2020-03
• 期刊: ACS Omega
• 影响因子: 4.1
• 作者: Michaela Schroepfer;F. Junghans;Diana Voigt;M. Meyer;Anette Breier;G. Schulze-Tanzil;I. Prade

Migrating Myofibroblastic Iliotibial Band-Derived Fibroblasts Represent a Promising Cell Source for Ligament Reconstruction

迁移肌纤维母细胞髂胫束衍生的成纤维细胞是韧带重建的有前途的细胞来源

• DOI: 10.3390/ijms20081972
• 发表时间: 1972
• 期刊: International Journal of Molecular Sciences
• 影响因子: 5.6
• 作者: S. Schwarz;C. Gögele;B. Ondruschka;N. Hammer;B. Kohl;G. Schulze-Tanzil
• 通讯作者: G. Schulze-Tanzil

Viscoelastic Behavior of Embroidered Scaffolds for ACL Tissue Engineering Made of PLA and P(LA-CL) After In Vitro Degradation

• DOI: 10.3390/ijms20184655
• 发表时间: 2019-09-02
• 期刊: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• 影响因子: 5.6
• 作者: Hahn, Judith;Schulze-Tanzil, Gundula;Breier, Annette
• 通讯作者: Breier, Annette