Negi Ankita, Verma Aakash, Garg Megha, Goswami Kajal, Mishra Vedante, Singh Arun Kumar, Agrawal Garima, Murab Sumit
School of Biosciences & Bioengineering, IIT Mandi, HP, India.
School of Chemical Sciences, IIT Mandi, HP, India.
Int J Biol Macromol. 2024 Dec;282(Pt 3):136968. doi: 10.1016/j.ijbiomac.2024.136968. Epub 2024 Oct 28.
25 % of the patients who receive orthopedic implants have been reported with implant-associated osteomyelitis, which can result in inflammation, osteolysis, and aseptic loosening of implants. Current treatment methods doesn't ensure defect healing and prevention from reinfection. Thermoplastic-based 3D-printed scaffolds offer a bioresorbable, biocompatible, and mechanical strong implant system. However, the hydrophobicity and bio-inertness of these polymers prevent their use in clinics. In this study, we developed dual functionalized scaffolds with osteogenic and antibacterial properties by immobilizing citric acid-linked chitosan on oxygen plasma etched 3D-printed PLA scaffolds through an EDC-NHS coupling reaction. Acellular mineralization of these scaffolds in DMEM demonstrated the deposition of crystalline hydroxyapatite. In addition, the antibacterial properties of these surface-modified scaffolds have been determined against E. coli and S. aureus, where the citric-linked chitosan biofunctionalized 3D-printed PLA scaffolds showed significantly higher antibacterial activity in comparison to oxygen-etched PLA and PLA scaffolds due to the synergistic effect of citric acid and chitosan functionalities. MG-63 cells exhibited increased proliferation and osteogenic activity on the modified scaffolds compared to the PLA and OP-PLA. These 3D-printed scaffolds, coated with citric-linked chitosan, can be a potential solution to orthopedic complications such as critical-sized bone defects and implant-associated osteomyelitis.
据报道，接受骨科植入物的患者中有25%会发生与植入物相关的骨髓炎，这可能导致炎症、骨溶解和植入物无菌性松动。目前的治疗方法无法确保缺损愈合和预防再次感染。基于热塑性塑料的3D打印支架提供了一种可生物吸收、生物相容且机械强度高的植入系统。然而，这些聚合物的疏水性和生物惰性阻碍了它们在临床上的应用。在本研究中，我们通过EDC-NHS偶联反应将柠檬酸连接的壳聚糖固定在氧等离子体蚀刻的3D打印PLA支架上，开发了具有成骨和抗菌性能的双功能化支架。这些支架在DMEM中的无细胞矿化证明了结晶羟基磷灰石的沉积。此外，还测定了这些表面改性支架对大肠杆菌和金黄色葡萄球菌的抗菌性能，由于柠檬酸和壳聚糖功能的协同作用，柠檬酸连接的壳聚糖生物功能化3D打印PLA支架与氧蚀刻PLA和PLA支架相比，显示出显著更高的抗菌活性。与PLA和OP-PLA相比，MG-63细胞在改性支架上表现出更高的增殖和成骨活性。这些涂有柠檬酸连接壳聚糖的3D打印支架可能是解决诸如临界尺寸骨缺损和植入物相关骨髓炎等骨科并发症的潜在解决方案。
