Department of Pharmaceutical Technology, University of Regensburg, Regensburg, Germany.
Biomaterials. 2010 May;31(14):3957-66. doi: 10.1016/j.biomaterials.2010.01.128. Epub 2010 Feb 18.
Adipose tissue engineering requires biomaterials that promote the differentiation of seeded adipocytes. Here, we report on the development and characterization of in situ forming, poly(ethylene glycol) (PEG) based hydrogels for soft tissue augmentation. Branched PEG-amines were modified with collagenase-sensitive peptides and cross-linked with branched PEG-succinimidyl propionates without the use of free-radical initiators (enzymatically degradable hydrogels). Alanine-modified PEG-amines were used for the preparation of non-degradable gels. Depending on the used polymer concentration, the strength of degradable gels after swelling ranged from 1708 to 7412 Pa; the strength of non-degradable hydrogels varied between 1496 and 7686 Pa. Enzyme mediated gel degradation occurred within 10, 16, and 19 days (5%, 10%, and 15% initial polymer content). To evaluate their suitability as scaffold materials for adipose tissue engineering, the hydrogels were functionalized with the laminin-derived adhesion peptide YIGSR, and seeded with 3T3-L1 preadipocytes. Compared to a standard two-dimensional cell culture model, the developed hydrogels significantly enhanced the intracellular triglyceride accumulation of encapsulated adipocytes. Functionalization with YIGSR further enhanced lipid synthesis within differentiating adipocytes. Long-term studies suggested that enzymatically degradable hydrogels furthermore promote the formation of coherent adipose tissue-like structures featuring many mature unilocular fat cells.
脂肪组织工程需要能够促进种子脂肪细胞分化的生物材料。在这里，我们报告了用于软组织增强的原位形成的聚乙二醇（PEG）基水凝胶的开发和特性。支化 PEG-胺用胶原酶敏感肽进行修饰，并与支化 PEG-琥珀酰亚胺丙酸酯交联，而无需使用自由基引发剂（可酶降解水凝胶）。丙氨酸修饰的 PEG-胺用于制备不可降解的凝胶。根据使用的聚合物浓度，溶胀后可降解凝胶的强度范围为 1708 至 7412 Pa；不可降解水凝胶的强度在 1496 至 7686 Pa 之间变化。酶介导的凝胶降解在 10、16 和 19 天内发生（初始聚合物含量为 5%、10%和 15%）。为了评估它们作为脂肪组织工程支架材料的适用性，将水凝胶用层粘连蛋白衍生的粘附肽 YIGSR 功能化，并接种 3T3-L1 前体脂肪细胞。与标准二维细胞培养模型相比，开发的水凝胶显著增强了包封脂肪细胞的细胞内甘油三酯积累。用 YIGSR 进行功能化进一步增强了分化脂肪细胞中的脂质合成。长期研究表明，可酶降解水凝胶还促进了具有许多成熟单腔脂肪细胞的连贯脂肪组织样结构的形成。
