Pérez-Davila Sara, Potel-Alvarellos Carmen, Carballo Raquel, González-Rodríguez Laura, López-Álvarez Miriam, Serra Julia, Díaz-Rodríguez Patricia, Landín Mariana, González Pío
CINTECX, Universidade de Vigo, Grupo Novos Materiais, 36310 Vigo, Spain.
Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36213 Vigo, Spain.
Polymers (Basel). 2023 Oct 28;15(21):4250. doi: 10.3390/polym15214250.
The regeneration of bone remains one of the main challenges in the biomedical field, with the need to provide more personalized and multifunctional solutions. The other persistent challenge is related to the local prevention of infections after implantation surgery. To fulfill the first one and provide customized scaffolds with complex geometries, 3D printing is being investigated, with polylactic acid (PLA) as the biomaterial mostly used, given its thermoplastic properties. The 3D printing of PLA in combination with hydroxyapatite (HA) is also under research, to mimic the native mechanical and biological properties, providing more functional scaffolds. Finally, to fulfill the second one, antibacterial drugs locally incorporated into biodegradable scaffolds are also under investigation. This work aims to develop vancomycin-loaded 3D-printed PLA-HA scaffolds offering a dual functionality: local prevention of infections and personalized biodegradable scaffolds with osseointegrative properties. For this, the antibacterial drug vancomycin was incorporated into 3D-printed PLA-HA scaffolds using three loading methodologies: (1) dip coating, (2) drop coating, and (3) direct incorporation in the 3D printing with PLA and HA. A systematic characterization was performed, including release kinetics, antibacterial/antibiofilm activities and cytocompatibility. The results demonstrated the feasibility of the vancomycin-loaded 3D-printed PLA-HA scaffolds as drug-releasing vehicles with significant antibacterial effects for the three methodologies. In relation to the drug release kinetics, the (1) dip- and (2) drop-coating methodologies achieved burst release (first 60 min) of around 80-90% of the loaded vancomycin, followed by a slower release of the remaining drug for up to 48 h, while the (3) 3D printing presented an extended release beyond 7 days as the polymer degraded. The cytocompatibility of the vancomycin-loaded scaffolds was also confirmed.
骨再生仍然是生物医学领域的主要挑战之一，需要提供更具个性化和多功能的解决方案。另一个长期存在的挑战与植入手术后局部感染的预防有关。为了满足第一个需求并提供具有复杂几何形状的定制支架，人们正在研究3D打印技术，其中聚乳酸（PLA）因其热塑性而成为最常用的生物材料。聚乳酸与羟基磷灰石（HA）结合的3D打印也在研究中，以模拟天然的机械和生物学特性，提供更具功能性的支架。最后，为了满足第二个需求，局部掺入可生物降解支架中的抗菌药物也在研究中。这项工作旨在开发负载万古霉素的3D打印PLA-HA支架，该支架具有双重功能：局部预防感染和具有骨整合特性的个性化可生物降解支架。为此，使用三种负载方法将抗菌药物万古霉素掺入3D打印的PLA-HA支架中：（1）浸涂，（2）滴涂，以及（3）在PLA和HA的3D打印中直接掺入。进行了系统的表征，包括释放动力学、抗菌/抗生物膜活性和细胞相容性。结果表明，负载万古霉素的3D打印PLA-HA支架作为药物释放载体是可行的，这三种方法都具有显著的抗菌效果。关于药物释放动力学，（1）浸涂和（2）滴涂方法在最初60分钟内实现了约80-90%负载万古霉素的突发释放，随后剩余药物的释放速度较慢，长达48小时，而（3）3D打印随着聚合物降解呈现出超过7天的延长释放。负载万古霉素支架的细胞相容性也得到了证实。
