Tondera Christoph, Hauser Sandra, Krüger-Genge Anne, Jung Friedrich, Neffe Axel T, Lendlein Andreas, Klopfleisch Robert, Steinbach Jörg, Neuber Christin, Pietzsch Jens
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany;; Technische Universität Dresden, Department of Chemistry and Food Chemistry, Dresden, Germany.
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany.
Theranostics. 2016 Sep 12;6(12):2114-2128. doi: 10.7150/thno.16614. eCollection 2016.
Hydrogels based on gelatin have evolved as promising multifunctional biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI) and the molar ratio of gelatin and LDI in the starting material mixture determines elastic properties of the resulting hydrogel. In order to investigate the clinical potential of these biopolymers, hydrogels with different ratios of gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral implantation). Degradation and biomaterial-tissue-interaction were investigated (MRI, optical imaging, PET) and (autoradiography, histology, serum analysis). Multimodal imaging revealed that the number of covalent net points correlates well with degradation time, which allows for targeted modification of hydrogels based on properties of the tissue to be replaced. Importantly, the degradation time was also dependent on the number of implants per animal. Despite local mechanisms of tissue remodeling no adverse tissue responses could be observed neither locally nor systemically. Finally, this preclinical investigation in immunocompetent mice clearly demonstrated a complete restoration of the original healthy tissue.
基于明胶的水凝胶已发展成为有前景的多功能生物材料。明胶与赖氨酸二异氰酸酯乙酯（LDI）交联，起始材料混合物中明胶与LDI的摩尔比决定了所得水凝胶的弹性特性。为了研究这些生物聚合物的临床潜力，将具有不同明胶与二异氰酸酯比例（异氰酸酯基团摩尔过量3倍（G10_LNCO3）和8倍（G10_LNCO8））的水凝胶皮下植入小鼠体内（单侧或双侧植入）。通过（MRI、光学成像、PET）以及（放射自显影、组织学、血清分析）研究降解情况和生物材料与组织的相互作用。多模态成像显示共价网点数量与降解时间密切相关，这使得能够根据待替代组织的特性对水凝胶进行有针对性的改性。重要的是，降解时间还取决于每只动物的植入物数量。尽管存在局部组织重塑机制，但在局部和全身均未观察到不良组织反应。最后，在具有免疫活性的小鼠中进行的这项临床前研究清楚地证明了原始健康组织的完全恢复。
