FOR 2180: Graded Implants for Tendon-Bone Junctions (“Graded Implants”)

FOR 2180：肌腱-骨连接处的分级植入物（“分级植入物”）

• 批准号: 251503496
• 金额: --
• 依托单位: Institut für Pharmazeutische Technologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/251503496?language=en
• 关键词: 2180; Graded; Implants; Tendon; Bone

Implant research recently focusses on functional tissue implants forhomogenous tissues. Less well elaborated are implants for regionsbetween tissues with strongly differing properties, e. g. tendon-bonejunctions. Natural tissue junctions exhibit gradients: gradients instructure, composition, and resulting functionality which are reflectedby alterations in biomechanical properties. This complex situation isaddressed by the novel, graded cell-free implant presented by theresearch unit. Endogenous stem cells from the host shall be activatedand instructed by the implant to rebuild a tendon-bone junction and toachieve a functional (“regenerated”) junction after degradation of theimplant. Aim of the research unit is to demonstrate the principlefeasibility and to generate a model of a graded implant for futureapplications at the tendon-bone junction of the rotator cuff. As basicmaterial, electrospun fibre mats from biodegradable polymers (mainlybased on polycaprolactone) with isotropic (“on the tendon side”) oranisotropic (“on the bone side”) fibre orientation will be used. The fibremats will be equipped with appropriate porosity and permeability toallow for the survival and functionality of immigrating cells as well asthe exchange of nutrients and products of metabolism. In addition, themechanical properties will be tailored according to the in vivosituation.Fibre surfaces will be modified and equipped with varyingdegrees of nanoparticles: polymeric nanoparticles will serve asrelease systems for biologically active proteins. Apart from BoneMorphogenetic Protein (BMP)-2 and Transforming Growth Factor(TGF)-β, the novel factor Smad8 Linker region + Mad homologyregion 2 (Smad8 L+MH2) will be used. This is a modified transcriptionfactor inducing differentiation of cells into tendon cells and tendontissue. By targeted design of the nanoparticles and by use of methodsfor their (graded) immobilization on the fibre mat release kinetics ofthe factors will be adjusted according to biological needs. In order toachieve long-term release also BMP2-aggregates and amyloidvariants of Smad8 L+MH2 will be produced. Fixation of the implant onthe bone side will by performed by commercially available boneanchors. At the tendon side, sutures will be used. The formation of aregenerated tissue junction after use of the implant will be verified inthe research unit by use of small and large animal models. Inconclusion, gradients existent in vivo will be translated into gradientsof mechanical properties in combination with spatially and temporallycontrolled release of biologically active proteins within FOR 2180.

近年来，种植体研究主要集中在均质组织的功能性组织种植体上。在组织之间具有强烈不同特性的区域，如肌腱-骨连接处，植入物的设计就不那么完善了。自然组织连接点表现出梯度：梯度的基础结构、组成和由此产生的功能，这些都是通过生物力学特性的改变来反映的。该研究小组提出的新型、分级无细胞植入物解决了这一复杂情况。来自宿主的内源性干细胞应被植入物激活并指示重建肌腱-骨连接，并在植入物降解后实现功能性（“再生”）连接。该研究单位的目的是证明原理可行性，并为将来在肌腱-骨交界处的肌腱-骨连接处应用生成分级植入物模型。作为基础材料，将使用由可生物降解聚合物（主要基于聚己内酯）制成的具有各向同性（“在肌腱一侧”）或各向异性（“在骨骼一侧”）纤维取向的静电纺纤维垫。纤维纤维将配备适当的孔隙度和渗透性，以允许迁移细胞的生存和功能，以及营养物质和代谢产物的交换。此外，机械性能将根据体内情况量身定制。纤维表面将被修改并配备不同程度的纳米颗粒：聚合纳米颗粒将作为生物活性蛋白质的释放系统。除了骨形态发生蛋白(BMP)-2和转化生长因子(TGF)-β外，还将使用新的因子Smad8连接区+ Mad同源区2 （Smad8 L+MH2）。这是一种修饰的转录因子，可诱导细胞分化为肌腱细胞和肌腱组织。通过纳米颗粒的目标设计和使用方法将其（分级）固定在纤维垫上，这些因子的释放动力学将根据生物需要进行调整。为了实现长期释放，还会产生bmp2聚集体和Smad8 L+MH2的淀粉样变异体。种植体在骨侧的固定将由市售的骨锚进行。在肌腱一侧，将使用缝合线。使用植入物后再生组织连接的形成将在研究单位通过使用小型和大型动物模型进行验证。综上所述，体内存在的梯度将转化为力学性能的梯度，并结合生物活性蛋白在空间和时间上的控制释放。