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评估一种热敏水凝胶递送抗胶原蛋白抗体以减少骨科组织创伤后瘢痕形成的疗效。

Evaluating the Efficacy of a Thermoresponsive Hydrogel for Delivering Anti-Collagen Antibodies to Reduce Posttraumatic Scarring in Orthopedic Tissues.

作者信息

Steplewski Andrzej, Fertala Jolanta, Cheng Lan, Wang Mark L, Rivlin Michael, Beredjiklian Pedro, Fertala Andrzej

机构信息

Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Department of Neurosciences, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.

出版信息

Gels. 2023 Dec 12;9(12):971. doi: 10.3390/gels9120971.

Abstract

Excessive posttraumatic scarring in orthopedic tissues, such as joint capsules, ligaments, tendons, muscles, and peripheral nerves, presents a significant medical problem, resulting in pain, restricted joint mobility, and impaired musculoskeletal function. Current treatments for excessive scarring are often ineffective and require the surgical removal of fibrotic tissue, which can aggravate the problem. The primary component of orthopedic scars is collagen I-rich fibrils. Our research team has developed a monoclonal anti-collagen antibody (ACA) that alleviates posttraumatic scarring by inhibiting collagen fibril formation. We previously established the safety and efficacy of ACA in a rabbit-based arthrofibrosis model. In this study, we evaluate the utility of a well-characterized thermoresponsive hydrogel (THG) as a delivery vehicle for ACA to injury sites. Crucial components of the hydrogel included N-isopropylacrylamide, poly(ethylene glycol) diacrylate, and hyaluronic acid. Our investigation focused on in vitro ACA release kinetics, stability, and activity. Additionally, we examined the antigen-binding characteristics of ACA post-release from the THG in an in vivo context. Our preliminary findings suggest that the THG construct exhibits promise as a delivery platform for antibody-based therapeutics to reduce excessive scarring in orthopedic tissues.

摘要

骨科组织(如关节囊、韧带、肌腱、肌肉和周围神经)创伤后过度瘢痕形成是一个重大的医学问题,会导致疼痛、关节活动受限以及肌肉骨骼功能受损。目前针对过度瘢痕形成的治疗方法往往无效,且需要手术切除纤维化组织,这可能会使问题恶化。骨科瘢痕的主要成分是富含I型胶原蛋白的纤维。我们的研究团队开发了一种单克隆抗胶原蛋白抗体(ACA),通过抑制胶原纤维形成来减轻创伤后瘢痕形成。我们之前在基于兔子的关节纤维化模型中确定了ACA的安全性和有效性。在本研究中,我们评估一种特性明确的热响应水凝胶(THG)作为ACA输送载体至损伤部位的效用。水凝胶的关键成分包括N - 异丙基丙烯酰胺、聚(乙二醇)二丙烯酸酯和透明质酸。我们的研究重点是体外ACA释放动力学、稳定性和活性。此外,我们在体内环境中检测了从THG释放后ACA的抗原结合特性。我们的初步研究结果表明,THG构建体有望作为基于抗体的治疗药物的输送平台,以减少骨科组织中的过度瘢痕形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9999/10742524/d8681bc7cfc2/gels-09-00971-g001.jpg

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