{"title":"Enhanced Biodegradation of Silk Fibroin Hydrogel for Preventing Postoperative Adhesion.","authors":"Yusuke Kambe, Yusuke Kawano, Makoto Sasaki, Maito Koga, Nobuyuki Fujita, Tsunenori Kameda","doi":"10.1021/acsbiomaterials.4c01805","DOIUrl":null,"url":null,"abstract":"<p><p>An absorbable adhesion barrier is a medical device that prevents postoperative adhesion and matches its biodegradation time with the regeneration period of its target tissues, which is important for antiadhesion effects. Physical hydrogels of <i>Bombyx mori</i> silk fibroin (SF) proteins are degradable <i>in vivo</i>. However, their biodegradation time is too long to exert antiadhesion effects. To shorten the biodegradation time of the SF hydrogels, we decreased the molecular weight (MW) of the SF proteins by alkaline treatment and prepared low-MW (LMW) SF hydrogels. The hydrogels contained less β-sheet crystalline and more amorphous structures than conventional, high-MW (HMW) SF hydrogels. Because of the potential loosened SF molecular structures in the hydrogel networks, the LMW SF hydrogels showed enhanced biodegradation (i.e., shorter <i>in vitro</i> enzymatic biodegradation time and faster <i>in vivo</i> biodegradation rate) as well as a lower affinity for plasma proteins and fibroblasts, which are involved in postoperative adhesion formation. An antiadhesion test using a rat abdominal adhesion model demonstrated that the LMW SF hydrogel applied to the abraded cecum was almost completely degraded within two weeks postimplantation, with a significantly lower adhesion severity score than that in the untreated model rat group. Conversely, the HMW SF hydrogel remained between the cecum and abdominal wall, with the same adhesion severity as that of the untreated model rat group. Therefore, we concluded that the antiadhesion effects of SF hydrogels were induced by enhanced biodegradation. The results of this study indicate the potential of LMW SF hydrogels as absorbable adhesion barriers.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Biomaterials Science & Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1021/acsbiomaterials.4c01805","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
An absorbable adhesion barrier is a medical device that prevents postoperative adhesion and matches its biodegradation time with the regeneration period of its target tissues, which is important for antiadhesion effects. Physical hydrogels of Bombyx mori silk fibroin (SF) proteins are degradable in vivo. However, their biodegradation time is too long to exert antiadhesion effects. To shorten the biodegradation time of the SF hydrogels, we decreased the molecular weight (MW) of the SF proteins by alkaline treatment and prepared low-MW (LMW) SF hydrogels. The hydrogels contained less β-sheet crystalline and more amorphous structures than conventional, high-MW (HMW) SF hydrogels. Because of the potential loosened SF molecular structures in the hydrogel networks, the LMW SF hydrogels showed enhanced biodegradation (i.e., shorter in vitro enzymatic biodegradation time and faster in vivo biodegradation rate) as well as a lower affinity for plasma proteins and fibroblasts, which are involved in postoperative adhesion formation. An antiadhesion test using a rat abdominal adhesion model demonstrated that the LMW SF hydrogel applied to the abraded cecum was almost completely degraded within two weeks postimplantation, with a significantly lower adhesion severity score than that in the untreated model rat group. Conversely, the HMW SF hydrogel remained between the cecum and abdominal wall, with the same adhesion severity as that of the untreated model rat group. Therefore, we concluded that the antiadhesion effects of SF hydrogels were induced by enhanced biodegradation. The results of this study indicate the potential of LMW SF hydrogels as absorbable adhesion barriers.
可吸收粘连屏障是一种防止术后粘连的医疗设备,其生物降解时间与目标组织的再生期相匹配,这对于抗粘连效果非常重要。蚕丝纤维蛋白(SF)的物理水凝胶可在体内降解。然而,它们的生物降解时间太长,无法发挥抗粘连效果。为了缩短 SF 水凝胶的生物降解时间,我们通过碱处理降低了 SF 蛋白的分子量(MW),制备出了低分子量(LMW)SF 水凝胶。与传统的高分子量(HMW)SF 水凝胶相比,这种水凝胶含有较少的β片状结晶和较多的无定形结构。由于水凝胶网络中可能存在松散的 SF 分子结构,低分子量 SF 水凝胶显示出更强的生物降解性(即更短的体外酶生物降解时间和更快的体内生物降解率),以及对血浆蛋白和成纤维细胞更低的亲和力,而血浆蛋白和成纤维细胞参与了术后粘连的形成。使用大鼠腹部粘连模型进行的抗粘连测试表明,应用于磨损盲肠的 LMW SF 水凝胶在植入后两周内几乎完全降解,粘连严重程度评分明显低于未经处理的模型大鼠组。相反,HMW SF 水凝胶仍留在盲肠和腹壁之间,粘附严重程度与未处理的模型大鼠组相同。因此,我们得出结论,SF 水凝胶的抗粘连作用是由生物降解增强引起的。本研究结果表明了低分子量 SF 水凝胶作为可吸收粘附屏障的潜力。
期刊介绍:
ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics:
Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology
Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions
Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis
Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering
Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends
Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring
Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration
Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials
Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture