Dahiya Aditi, Chaudhari Vishal Sharad, Kushram Priya, Bose Susmita
Department of Chemistry, Washington State University, Pullman, Washington 99164, United States.
W. M. Keck Biomedical Materials Research Laboratory, School of Mechanical and Materials Engineering, Washington State University, Pullman, Washington 99164, United States.
J Med Chem. 2024 Feb 22;67(4):2745-2757. doi: 10.1021/acs.jmedchem.3c01884. Epub 2023 Dec 26.
Bone damage resulting from trauma or aging poses challenges in clinical settings that need to be addressed using bone tissue engineering (BTE). Carvacrol (CA) possesses anti-inflammatory, anticancer, and antibacterial properties. Limited solubility and physicochemical stability restrict its biological activity, requiring a stable carrier system for delivery. Here, we investigate the utilization of a three-dimensional printed (3DP) SiO-doped tricalcium phosphate (TCP) scaffold functionalized with carvacrol-loaded lipid nanoparticles (CA-LNPs) to improve bone health. It exhibits a negative surface charge with an entrapment efficiency of ∼97% and size ∼129 nm with polydispersity index (PDI) and zeta potential values of 0.18 and -16 mV, respectively. CA-LNPs exhibit higher and long-term release over 35 days. The CA-LNP loaded SiO-doped TCP scaffold demonstrates improved antibacterial properties against and by >90% reduction in bacterial growth. Functionalized scaffolds result in 3-fold decrease and 2-fold increase in osteosarcoma and osteoblast cell viability, respectively. These findings highlight the therapeutic potential of the CA-LNP loaded SiO-doped TCP scaffold for bone defect treatment.
由创伤或衰老导致的骨损伤在临床环境中构成了挑战,需要通过骨组织工程(BTE)来解决。香芹酚(CA)具有抗炎、抗癌和抗菌特性。有限的溶解度和物理化学稳定性限制了其生物活性,需要一个稳定的载体系统来递送。在此,我们研究利用三维打印(3DP)的掺杂二氧化硅的磷酸三钙(TCP)支架,该支架用负载香芹酚的脂质纳米颗粒(CA-LNPs)进行功能化,以改善骨骼健康。它呈现负表面电荷,包封率约为97%,尺寸约为129 nm,多分散指数(PDI)和zeta电位值分别为0.18和 -16 mV。CA-LNPs在35天内表现出更高的长期释放。负载CA-LNPs的掺杂二氧化硅的TCP支架对[具体细菌名称1]和[具体细菌名称2]表现出改善的抗菌性能,细菌生长减少>90%。功能化支架分别使骨肉瘤和成骨细胞活力降低3倍和增加2倍。这些发现突出了负载CA-LNPs的掺杂二氧化硅的TCP支架在骨缺损治疗中的治疗潜力。