Nazir Abubakar, Nazir Awais, Khan Naseer, Jamal Muhammad Shah Wali, Shubietah Abdalhakim, Naqvi Imran, Rafay Hussain Zaidi Syed, Khan Behram, Ghumman Ghulam Mujtaba, Jamal Chaudhary Ahmed, Ali Syed Sohail
Department of Medicine, King Edward Medical University, Pakistan.
Department of Medicine, The Jewish Hospital of Cincinnati, Cincinnati, OH, USA.
Ann Med Surg (Lond). 2025 Nov 18;88(1):401-411. doi: 10.1097/MS9.0000000000004284. eCollection 2026 Jan.
Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide, necessitating advanced therapeutic strategies for cardiac repair. Conventional treatments often fail to restore cardiac function effectively, highlighting the need for innovative biomaterials. Smart bioactive hydrogels have emerged as promising candidates due to their ability to provide structural support, controlled drug delivery, electroconductivity, and real-time biosensing capabilities.
This review explores the multifunctional role of smart bioactive hydrogels in MI repair, focusing on their stimuli-responsive drug delivery, electroconductive properties, and biosensing potential.
This narrative review synthesized recent advances in multifunctional smart bioactive hydrogels for MI repair, focusing on systems integrating stimuli-responsive drug delivery, electroconductivity, and real-time biosensing. A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for studies published between 2010 and 2025 using relevant keywords. Articles were included if they addressed hydrogel-based platforms featuring at least one of the following: responsive drug release (e.g., pH, temperature, and enzymatic), conductive components (e.g., carbon nanotubes and graphene), or embedded biosensing technologies. Studies limited to conventional hydrogels without multifunctionality were excluded. Relevant data were extracted and thematically categorized by material composition, functional properties, regenerative potential, and translational applicability, with emphasis on preclinical cardiac models. No quantitative synthesis was performed due to heterogeneity across study designs.
Smart bioactive hydrogels have demonstrated significant potential for MI repair by integrating stimuli-responsive drug delivery, electroconductivity, and biosensing within a single therapeutic platform. pH-, ROS-, and enzyme-sensitive systems enable localized, on-demand release of angiogenic factors or cardioprotective drugs, leading to 20-45% infarct size reduction and 1.5-2.3-fold increases in neovascular density in preclinical models. Incorporation of conductive materials such as graphene oxide (GO), polypyrrole, or carbon nanotubes (CNT) has been shown to restore electrical coupling, improve connexin-43 expression, and enhance left ventricular ejection fraction by 8-15%, while narrowing QRS complex duration by ~15 ms in large-animal studies. Emerging biosensing-enabled hydrogels permit real-time monitoring of local biochemical cues, such as pH, oxygen levels, and inflammatory cytokines, maintaining stable signal fidelity for up to 4 weeks without adverse tissue reactions. Advances in 3D/4D bioprinting now allow spatially patterned integration of these functionalities, enabling region-specific therapeutic release and conductivity optimization. Collectively, these multifunctional hydrogels exhibit superior regenerative outcomes compared to conventional scaffolds and hold strong translational promise, although variability in experimental design, lack of standardized endpoints, and limited long-term clinical data remain challenges to widespread adoption.
Smart bioactive hydrogels represent a transformative approach in MI repair by combining structural support with multifunctional properties. Their ability to deliver therapeutics on demand, enhance electroconductivity, and enable real-time biosensing offers new possibilities for precision cardiac medicine.
心肌梗死（MI）仍然是全球发病和死亡的主要原因，需要先进的心脏修复治疗策略。传统治疗往往无法有效恢复心脏功能，这凸显了对创新生物材料的需求。智能生物活性水凝胶因其能够提供结构支持、可控药物递送、导电性和实时生物传感能力而成为有前景的候选材料。
本综述探讨智能生物活性水凝胶在心肌梗死修复中的多功能作用，重点关注其刺激响应性药物递送、导电特性和生物传感潜力。
本叙述性综述综合了用于心肌梗死修复的多功能智能生物活性水凝胶的最新进展，重点关注整合刺激响应性药物递送、导电性和实时生物传感的系统。使用相关关键词在PubMed、Scopus、Web of Science和谷歌学术上对2010年至2025年间发表的研究进行了全面的文献检索。如果文章涉及基于水凝胶的平台，且具有以下至少一项特征，则纳入研究：响应性药物释放（如pH、温度和酶）、导电成分（如碳纳米管和石墨烯）或嵌入式生物传感技术。仅限于无多功能性的传统水凝胶的研究被排除。提取相关数据，并按材料组成、功能特性、再生潜力和转化适用性进行主题分类，重点是临床前心脏模型。由于研究设计的异质性，未进行定量综合分析。
智能生物活性水凝胶通过在单一治疗平台中整合刺激响应性药物递送、导电性和生物传感，已显示出在心肌梗死修复中的巨大潜力。pH、活性氧和酶敏感系统能够实现血管生成因子或心脏保护药物的局部按需释放，在临床前模型中使梗死面积减少20 - 45%，新生血管密度增加1.5 - 2.3倍。已证明掺入氧化石墨烯（GO）、聚吡咯或碳纳米管（CNT）等导电材料可恢复电偶联、改善连接蛋白43表达，并在大型动物研究中将左心室射血分数提高8 - 15%，同时使QRS波群持续时间缩短约15 ms。新兴的具有生物传感功能的水凝胶允许对局部生化线索（如pH、氧水平和炎性细胞因子）进行实时监测，在长达4周的时间内保持稳定的信号保真度，且无不良组织反应。3D/4D生物打印技术的进步现在允许对这些功能进行空间模式化整合，实现区域特异性治疗释放和电导率优化。总体而言，与传统支架相比，这些多功能水凝胶表现出卓越的再生效果，并具有很强的转化前景，尽管实验设计的可变性、缺乏标准化终点以及有限的长期临床数据仍然是广泛应用的挑战。
智能生物活性水凝胶通过将结构支持与多功能特性相结合，代表了心肌梗死修复中的一种变革性方法。它们按需递送治疗药物、增强导电性和实现实时生物传感的能力为精准心脏医学提供了新的可能性。
