Chondroitinase ABC in spinal cord injury: advances in delivery strategies and therapeutic synergies.

IF 4.3 3区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Frontiers in Bioengineering and Biotechnology Pub Date : 2025-06-09 eCollection Date: 2025-01-01 DOI:10.3389/fbioe.2025.1604502
Rachel Santana Cunha, Erik Aranha Rossi, Thaís Alves de Santana, Zaquer Suzana Munhoz Costa-Ferro, Bruno Solano de Freitas Souza
{"title":"Chondroitinase ABC in spinal cord injury: advances in delivery strategies and therapeutic synergies.","authors":"Rachel Santana Cunha, Erik Aranha Rossi, Thaís Alves de Santana, Zaquer Suzana Munhoz Costa-Ferro, Bruno Solano de Freitas Souza","doi":"10.3389/fbioe.2025.1604502","DOIUrl":null,"url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a debilitating condition that leads to permanent neurological deficits due to the formation of a glial scar and the accumulation of chondroitin sulfate proteoglycans (CSPGs), which inhibit axonal regeneration. Chondroitinase ABC (ChABC), a bacterial enzyme capable of degrading CSPGs, has emerged as a promising therapeutic strategy for enhancing neural plasticity and functional recovery after SCI. However, clinical translation remains challenging due to the enzyme's thermal instability, short half-life, and limited penetration into the lesion site. This review provides a comprehensive overview of current strategies for ChABC delivery, including direct infusion, nanoparticles, hydrogels, scaffolds, viral vectors, and stem cell-based approaches. We highlight recent technological advances that improve enzyme stability, targeting, and sustained release, as well as combinatorial therapies that enhance tissue regeneration. Although ChABC monotherapy has shown limited efficacy, its association with other regenerative approaches has demonstrated significant potential in preclinical models. Finally, we discuss the translational challenges and future directions required to bring ChABC-based therapies closer to clinical application in SCI patients.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1604502"},"PeriodicalIF":4.3000,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183185/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Bioengineering and Biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.3389/fbioe.2025.1604502","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Spinal cord injury (SCI) is a debilitating condition that leads to permanent neurological deficits due to the formation of a glial scar and the accumulation of chondroitin sulfate proteoglycans (CSPGs), which inhibit axonal regeneration. Chondroitinase ABC (ChABC), a bacterial enzyme capable of degrading CSPGs, has emerged as a promising therapeutic strategy for enhancing neural plasticity and functional recovery after SCI. However, clinical translation remains challenging due to the enzyme's thermal instability, short half-life, and limited penetration into the lesion site. This review provides a comprehensive overview of current strategies for ChABC delivery, including direct infusion, nanoparticles, hydrogels, scaffolds, viral vectors, and stem cell-based approaches. We highlight recent technological advances that improve enzyme stability, targeting, and sustained release, as well as combinatorial therapies that enhance tissue regeneration. Although ChABC monotherapy has shown limited efficacy, its association with other regenerative approaches has demonstrated significant potential in preclinical models. Finally, we discuss the translational challenges and future directions required to bring ChABC-based therapies closer to clinical application in SCI patients.

脊髓损伤中的软骨素酶ABC:递送策略和治疗协同作用的进展。
脊髓损伤(SCI)是一种衰弱性疾病,由于神经胶质瘢痕的形成和硫酸软骨素蛋白聚糖(CSPGs)的积累,导致永久性神经功能缺损,从而抑制轴突再生。软骨素酶ABC (ChABC)是一种能够降解CSPGs的细菌酶,已成为增强脊髓损伤后神经可塑性和功能恢复的一种有前景的治疗策略。然而,由于酶的热不稳定性、半衰期短以及对病变部位的渗透有限,临床翻译仍然具有挑战性。这篇综述提供了目前ChABC给药策略的全面概述,包括直接输注、纳米颗粒、水凝胶、支架、病毒载体和基于干细胞的方法。我们强调了最近的技术进步,提高酶的稳定性,靶向性和持续释放,以及组合疗法,提高组织再生。尽管ChABC单药治疗的疗效有限,但其与其他再生方法的关联在临床前模型中显示出巨大的潜力。最后,我们讨论了使基于chabc的疗法更接近于SCI患者的临床应用所需的转化挑战和未来方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Frontiers in Bioengineering and Biotechnology
Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering
CiteScore
8.30
自引率
5.30%
发文量
2270
审稿时长
12 weeks
期刊介绍: The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信