Glycosaminoglycan-based hydrogels with programmable host reactions.
Glycosaminoglycan-based hydrogels with programmable host reactions.
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DOI：
10.1016/j.biomaterials.2019.119557
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发表时间：
2019
期刊：
影响因子：
14
通讯作者：
Lucas Schirmer;K. Chwalek;M. Tsurkan;U. Freudenberg;C. Werner
中科院分区：
文献类型：
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作者：
Lucas Schirmer;K. Chwalek;M. Tsurkan;U. Freudenberg;C. Werner
基于糖胺聚糖（GAG）的生物杂化水凝胶对其物理和生物分子信号特性具有深远的控制作用，已成功地应用于各种细胞和组织培养。为了探索这种材料在病毒载体中的适用性，我们研究了在免疫功能正常的C57BL/6J小鼠皮下植入后，宿主对PEG -GAG水凝胶变体的反应长达28天。具体来说，我们研究了具有系统变化的细胞因子功能化、物理网络（和机械）特性、细胞粘附性和酶降解性的水凝胶的免疫反应和血管生成反应。与类似植入的医用级硅胶相比，基于gag的水凝胶仅引起轻微的异物反应，免疫细胞浸润和胶原沉积较少。通过调整物理特性、生物功能和可降解性，可以在几天内将凝胶支架从几乎没有降解和浸润到快速整合到组织中，从而对宿主反应进行编程。结果表明，通过调整水凝胶体系，可以有效地控制异物反应和starPEG-GAG水凝胶组织整合，这表明它们的原位组装材料在体内组织工程应用中是安全有效的。
Glycosaminoglycan (GAG)-based, biohybrid hydrogels offering far-reaching control over their physical and biomolecular signaling properties have been successfully used in various cell and tissue culture applications. To explore the suitability of the materials forin vivouse, we herein studied the host reaction toin situ-assembling star(PEG)-GAG hydrogel variants upon subcutaneous implantation in immunocompetent C57BL/6J mice for up to 28 days. Specifically, we investigated the immune reaction and the angiogenic response to hydrogels with systematically varied cytokine functionalizations, physical network (and mechanical) properties, cell adhesiveness, and enzymatic degradability. The GAG-based hydrogel elicited only minor foreign body reaction with low immune cell infiltration and collagen deposition compared to similarly implanted medical grade silicone. Adjusting of the physical properties, biofunctionalization, and degradability allowed to program the host response from nearly no degradation and infiltration to fast integration of the gel scaffolds into the tissue within days. The results demonstrate that foreign body reactions and starPEG-GAG hydrogel tissue integration can be effectively controlled by defined adjustments of the hydrogel system, suggesting thein situ-assembling materials as safe and effective forin vivotissue engineering applications.