Development of carboxymethyl cellulose/gelatin hybrid hydrogels via radiation-induced cross-linking as novel anti-adhesion barriers
Development of carboxymethyl cellulose/gelatin hybrid hydrogels via radiation-induced cross-linking as novel anti-adhesion barriers
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DOI：
10.1016/j.polymdegradstab.2022.109856
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发表时间：
2022-02
影响因子：
5.9
通讯作者：
Ahmed E. Swilem;T. Oyama;K. Oyama;Atsushi Kimura;M. Taguchi
中科院分区：
文献类型：
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作者：
Ahmed E. Swilem;T. Oyama;K. Oyama;Atsushi Kimura;M. Taguchi
腹部和盆腔手术后粘连导致严重的临床结局，并对患者的生活质量产生负面影响。植入防粘连材料是预防术后粘连的常用策略，非粘性羧甲基纤维素（CMC）是一种广泛使用的防粘连材料。在此，我们提出CMC/明胶（CMC/G）杂化水凝胶作为新型屏障材料，其目的是通过结合明胶的生物相容性和生物降解性以及CMC的非生物相容性，并通过实现与宿主组织的机械匹配来减少异物反应（FBR）。采用无试剂γ射线辐照交联法制备了羧甲基纤维素（CMC）-明胶水凝胶。通过改变初始混合比来控制水凝胶组成。明胶组分在含量≥ 40%时具有酶介导的降解性，降解速率受辐射剂量控制。通过10-30 kGy的辐射，将水凝胶的压缩模量调整为与目标腹部器官的压缩模量相同（几十kPa）。由于CMC的非粘附能力超过了水凝胶中明胶的高细胞粘附性，水凝胶充分防止了3 T3-Swiss成纤维细胞的粘附。另一方面，添加的明胶显著提高了粘附在水凝胶上的少数细胞的活力。我们发现由60%CMC和40%明胶组成的水凝胶表现出显著更高的细胞活力，同时保持作为屏障材料所期望的非粘附性。体外评价结果表明，该水凝胶具有良好的生物相容性，促进伤口愈合，并通过实现与宿主腹部器官的机械匹配来降低FBR，特别是当其由60% CMC和40%明胶组成并在10-30 kGy下交联以赋予20-100 kPa的压缩模量时，其作为新型屏障材料的潜力。
Adhesion after abdominal and pelvic surgery results in severe clinical outcomes and a negative impact on the quality of life of a patient. Implanting barrier materials is a common strategy for preventing postoperative adhesion, and non-adhesive carboxymethylcellulose (CMC) is a widely used material for such purpose. Herein, we present CMC/gelatin (CMC/G) hybrid hydrogels as novel barrier materials that aim to reduce the foreign body response (FBR) by combining the biocompatibility and biodegradability of gelatin and the non-adhesiveness of CMC and by realizing mechanical matching with the host tissue. The hydrogels were prepared by the simple reagent-free γ-ray irradiation-induced cross-linking of CMC and gelatin. The hydrogel composition was controlled by varying the initial mixing ratio. The gelatin fraction provided enzyme-mediated degradability at a content ≥ 40%, and the degradation rate was controlled by the radiation dose. The compressive moduli of the hydrogels were tuned to be identical to that of target abdominal organs (several tens of kPa) via 10–30 kGy radiation. The hydrogels sufficiently prevented adhesion of 3T3-Swiss fibroblast cells owing to the non-adhesive capability of CMC which surpassed the high cell adhesiveness of gelatin in the hydrogels. On the other hand, the added gelatin significantly improved the viability of the few cells that adhered to the hydrogels. We found that hydrogels composed of 60% CMC and 40% gelatin exhibited significantly higher cell viabilities while maintaining the non-adhesiveness which is desirable as barrier materials. Thein vitroassessments demonstrated the potential of the hydrogel as a novel barrier material with excellent biocompatibility, wound healing promoting effect, and FBR reducing effect by realizing mechanical matching with the host abdominal organs, especially when it was composed of 60% CMC and 40% gelatin and cross-linked at 10–30 kGy to impart compressive modulus of 20–100 kPa.