Mendes Maria C, Santos Sara C, Custódio Catarina A, Silva A Sofia, Mano João F
Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, Aveiro, 3810-193, Portugal.
Metatissue, Edifício Central, PCI Creative Science Park Aveiro Region, Via do Conhecimento, Ílhavo, 3830-352, Portugal.
Adv Healthc Mater. 2025 Jul 14:e2500977. doi: 10.1002/adhm.202500977.
The development of effective cell delivery therapies faces challenges regarding cell viability and retention after injection. Hydrogel-based materials, designed to mimic extracellular matrix components for cell protection during injection and to enhance local availability, often rely on animal-derived components that raise immunogenicity concerns. Alternatively, those employing polysaccharides and synthetic polymers may exhibit suboptimal cell adhesive properties. This study showcases the development of injectable human protein-derived cell carrier microgels made from methacryloyl platelet lysates. These microgels sustain cell viability by providing an enriched and cost-effective environment of growth factors and proteins while promoting the outward migration of mesenchymal stem cells through controlled enzyme-mediated degradation. Employing a solvent-free and reproducible method using superhydrophobic surfaces, human-derived microgels are successfully fabricated via light irradiation, with sizes adjustable by varying droplet volume. Additionally, the incorporation of collagenase facilitates enzyme-mediated cell migration without compromising viability. Injectability tests confirm that microgel administration preserves both size and morphology, and their effectiveness in filling irregular defects in a porcine tissue highlights their suitability for therapeutic applications. Ultimately, these microgels can be modified to include magnetic nanoparticles, enabling spatial control and fixation using an external magnetic field, and potential imaging capabilities, positioning them as promising candidates for personalized cell therapies.
有效的细胞递送疗法的发展在注射后的细胞活力和留存方面面临挑战。基于水凝胶的材料旨在模仿细胞外基质成分，以便在注射过程中保护细胞并提高局部可用性，但其通常依赖动物来源的成分，这引发了对免疫原性的担忧。另外，那些使用多糖和合成聚合物的材料可能表现出次优的细胞粘附特性。本研究展示了由甲基丙烯酰化血小板裂解物制成的可注射的人源蛋白衍生细胞载体微凝胶的开发。这些微凝胶通过提供富含生长因子和蛋白质且经济高效的环境来维持细胞活力，同时通过可控的酶介导降解促进间充质干细胞向外迁移。采用使用超疏水表面的无溶剂且可重复的方法，通过光照射成功制备了人源微凝胶，其尺寸可通过改变液滴体积进行调节。此外，加入胶原酶可促进酶介导的细胞迁移而不影响细胞活力。可注射性测试证实微凝胶给药可保持其大小和形态，并且它们在填充猪组织中的不规则缺陷方面的有效性突出了它们在治疗应用中的适用性。最终，这些微凝胶可以进行修饰以包含磁性纳米颗粒，从而能够使用外部磁场进行空间控制和固定，并具有潜在的成像能力，使其成为个性化细胞疗法的有前景的候选者。
