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Characterization of silk-hyaluronic acid composite hydrogels towards vitreous humor substitutes.
Biomaterials ( IF 12.8 ) Pub Date : 2019-12-27 , DOI: 10.1016/j.biomaterials.2019.119729
Nicole R Raia 1 , Di Jia 2 , Chiara E Ghezzi 3 , Murugappan Muthukumar 2 , David L Kaplan 1
Affiliation  

Multiple ophthalmic pathologies, such as retinal detachment and diabetic retinopathy, require the removal and replacement of the vitreous humor. Clinical tamponades such as silicone oil and fluorinated gases are utilized but limited due to complications and toxicity. Therefore, there is a need for biocompatible, stable, vitreous humor substitutes. In this study, enzymatically crosslinked silk-hyaluronic acid (HA) hydrogels formed using horseradish peroxidase and H2O2 were characterized for use as vitreous humor substitutes. The composite network structure was characterized with dynamic light scattering. In addition, the rheological, optical, and swelling properties of hydrogels with varying silk to HA ratios and crosslinking densities controlled via H2O2 were determined over time. Hydrogels had refractive indexes of 1.336 and were clear with 75-91% light transmission. Hydrogel shear storage modulus ranged between ~6 and 240 Pa where increased H2O2 increased the modulus. After 1 month of aging, there were no changes in modulus for hydrogels with lower silk ratios, while those with higher silk ratios exhibited a significant increase in modulus. Decreasing H2O2 concentration in the reactions led to increased hydrogel volume during swelling, with higher silk ratios returning to their original size after 15 days. Dynamic light scattering results show three diffusive modes, revealing the possible structures of the hydrogel composite and are consistent with the mechanical properties and swelling results. The normalized intraocular pressure of ex vivo porcine eyes after injecting hydrogels were comparable with those treated with silicone oil showing the potential clinical utility of the hydrogels as vitreous substitutes. The versatility of the silk-HA hydrogel system, the tunable swelling properties, and the stability of hydrogels with lower silk ratios show the benefit of utilizing silk-HA hydrogels as vitreous substitutes.

中文翻译:


丝-透明质酸复合水凝胶对玻璃体液替代品的表征。



多种眼科病变,例如视网膜脱离和糖尿病视网膜病变,需要去除和更换玻璃体液。临床上使用了硅油和氟化气体等填塞剂,但由于并发症和毒性而受到限制。因此,需要生物相容的、稳定的玻璃体替代物。在这项研究中,使用辣根过氧化物酶和 H2O2 形成的酶交联丝-透明质酸 (HA) 水凝胶的特征是用作玻璃体液替代品。通过动态光散射对复合网络结构进行了表征。此外,随着时间的推移,还确定了具有不同丝与HA比率和通过H2O2控制的交联密度的水凝胶的流变学、光学和溶胀特性。水凝胶的折射率为1.336,透明,透光率为75-91%。水凝胶剪切储能模量范围在 ~6 至 240 Pa 之间,其中 H2O2 的增加会增加模量。老化1个月后,丝比率较低的水凝胶的模量没有变化,而丝比率较高的水凝胶的模量显着增加。反应中 H2O2 浓度的降低导致溶胀期间水凝胶体积增加,较高的丝比率在 15 天后恢复到原始尺寸。动态光散射结果显示了三种扩散模式,揭示了水凝胶复合材料的可能结构,并且与机械性能和溶胀结果一致。注射水凝胶后离体猪眼的标准化眼压与用硅油处理的眼压相当,这表明水凝胶作为玻璃体替代品的潜在临床实用性。 丝-HA 水凝胶系统的多功能性、可调节的溶胀特性以及具有较低丝比率的水凝胶的稳定性显示了利用丝-HA 水凝胶作为玻璃体替代品的好处。
更新日期:2019-12-27
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