Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Biomaterials. 2010 Apr;31(10):2788-97. doi: 10.1016/j.biomaterials.2009.12.033. Epub 2010 Jan 4.
We developed a chondroitin sulfate-polyethylene glycol (CS-PEG) adhesive hydrogel with numerous potential biomedical applications. The carboxyl groups on chondroitin sulfate (CS) chains were functionalized with N-hydroxysuccinimide (NHS) to yield chondroitin sulfate succinimidyl succinate (CS-NHS). Following purification, the CS-NHS molecule can react with primary amines to form amide bonds. Hence, using six arm polyethylene glycol amine PEG-(NH2)6 as a crosslinker we formed a hydrogel which was covalently bound to proteins in tissue via amide bonds. By varying the initial pH of the precursor solutions, the hydrogel stiffness, swelling properties, and kinetics of gelation could be controlled. The sealing/adhesive strength could also be modified by varying the damping and storage modulus properties of the material. The adhesive strength of the material with cartilage tissue was shown to be ten times higher than that of fibrin glue. Cells encapsulated or in direct contact with the material remained viable and metabolically active. Furthermore, CS-PEG material produced minimal inflammatory response when implanted subcutaneously in a rat model and enzymatic degradation was demonstrated in vitro. This work establishes an adhesive hydrogel derived from biological and synthetic components with potential application in wound healing and regenerative medicine.
我们开发了一种硫酸软骨素-聚乙二醇（CS-PEG）胶粘剂水凝胶，具有许多潜在的生物医学应用。硫酸软骨素（CS）链上的羧基基团用 N-羟基琥珀酰亚胺（NHS）进行了功能化，得到硫酸软骨素琥珀酰亚胺酯（CS-NHS）。经过纯化后，CS-NHS 分子可以与伯胺反应形成酰胺键。因此，我们使用六臂聚乙二醇胺 PEG-（NH2）6 作为交联剂，形成了一种水凝胶，该水凝胶通过酰胺键与组织中的蛋白质共价结合。通过改变前体溶液的初始 pH 值，可以控制水凝胶的硬度、溶胀性能和凝胶化动力学。通过改变材料的阻尼和储能模量特性，还可以调整密封/胶接强度。该材料与软骨组织的胶接强度比纤维蛋白胶高 10 倍。包封或直接与材料接触的细胞保持存活和代谢活性。此外，CS-PEG 材料在大鼠皮下植入模型中产生的炎症反应最小，并且在体外进行了酶降解。这项工作建立了一种由生物和合成成分衍生的胶粘剂水凝胶，具有在伤口愈合和再生医学中的潜在应用。
