Sonaye Surendrasingh Y, Bohara Smriti, Welsh Breanne L, Ertugral Elif G, Kothapalli Chandrasekhar R, Richter Hanz, Garg Koyal, Sikder Prabaha
Mechanical Engineering, Cleveland State University, Cleveland, Ohio, USA.
Chemical and Biomedical Engineering, Cleveland State University, Cleveland, Ohio, USA.
Adv Wound Care (New Rochelle). 2025 Mar;14(3):143-158. doi: 10.1089/wound.2024.0073. Epub 2024 Jul 26.
This study focuses on developing bioactive piezoelectric scaffolds that could deliver bioelectrical cues to potentially treat injuries to soft tissues such as skeletal muscles and promote active regeneration. To address the underexplored aspect of bioelectrical cues in skeletal muscle tissue engineering (SMTE), we developed piezoelectric bioink based on natural bioactive materials such as sodium alginate, gelatin, and chitosan. Extrusion-based 3D bioprinting was utilized to develop scaffolds that mimic muscle stiffness and generate electrical stimulation (E-stim) when subjected to forces. The biocompatibility of these scaffolds was tested with the C2C12 muscle cell line. The bioink demonstrated suitable rheological properties for 3D bioprinting, resulting in high-resolution composite sodium alginate-gelatin-chitosan scaffolds with good structural fidelity. The scaffolds exhibited a 42-60 kPa stiffness, similar to muscle. When a controlled force of 5N was applied to the scaffolds at a constant frequency of 4 Hz, they generated electrical fields and impulses (charge), indicating their suitability as a stand-alone scaffold to generate E-stim and instill bioelectrical cues in the wound region. The cell viability and proliferation test results confirm the scaffold's biocompatibility with C2C12s and the benefit of piezoelectricity in promoting muscle cell growth kinetics. Our study indicates that our piezoelectric bioink and scaffolds offer promise as autonomous E-stim-generating regenerative therapy for SMTE. A novel approach for treating skeletal muscle wounds was introduced by developing a bioactive electroactive scaffold capable of autonomously generating E-stim without stimulators and electrodes. This scaffold offers a unique approach to enhancing skeletal muscle regeneration through bioelectric cues, addressing a major gap in the SMTE, that is, fibrotic tissue formation due to delayed muscle regeneration. A piezoelectric scaffold was developed, providing a promising solution for promoting skeletal muscle regeneration. This development can potentially address skeletal muscle injuries and offers a unique approach to facilitating skeletal muscle wound healing.
本研究聚焦于开发具有生物活性的压电支架，该支架能够传递生物电信号，从而有可能治疗诸如骨骼肌等软组织损伤并促进积极再生。为解决骨骼肌组织工程（SMTE）中生物电信号这一尚未充分探索的方面，我们基于海藻酸钠、明胶和壳聚糖等天然生物活性材料开发了压电生物墨水。利用基于挤出的3D生物打印技术来开发模仿肌肉硬度并在受力时产生电刺激（E-stim）的支架。用C2C12肌肉细胞系测试了这些支架的生物相容性。该生物墨水表现出适合3D生物打印的流变学特性，从而得到具有良好结构保真度的高分辨率复合海藻酸钠-明胶-壳聚糖支架。这些支架表现出42 - 60千帕的硬度，与肌肉相似。当以4赫兹的恒定频率对支架施加5牛的受控力时，它们会产生电场和脉冲（电荷），表明它们适合作为独立的支架来产生E-stim并在伤口区域灌输生物电信号。细胞活力和增殖测试结果证实了该支架与C2C12细胞的生物相容性以及压电性在促进肌肉细胞生长动力学方面的益处。我们的研究表明，我们的压电生物墨水和支架有望作为用于SMTE的自主产生E-stim的再生疗法。通过开发一种能够在没有刺激器和电极情况下自主产生E-stim的生物活性电活性支架，引入了一种治疗骨骼肌伤口的新方法。这种支架提供了一种独特的方法，通过生物电信号增强骨骼肌再生，解决了SMTE中的一个主要差距，即由于肌肉再生延迟导致的纤维化组织形成。开发了一种压电支架，为促进骨骼肌再生提供了一个有前景的解决方案。这一进展有可能解决骨骼肌损伤问题，并提供一种独特的方法来促进骨骼肌伤口愈合。
