Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan, Kwei-San 33302, Taiwan.
Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital at Keelung, Keelung 20401, Taiwan.
ACS Biomater Sci Eng. 2024 Oct 14;10(10):6425-6440. doi: 10.1021/acsbiomaterials.4c00774. Epub 2024 Sep 3.
We fabricated three-dimensional (3D)-printed polycaprolactone (PCL) and PCL/graphene oxide (GO) (PGO) scaffolds for bone tissue engineering. An anti-inflammatory and pro-osteogenesis drug dexamethasone (DEX) was adsorbed onto GO and a 3D-printed PGO/DEX (PGOD) scaffold successfully improved drug delivery with a sustained release of DEX from the scaffold up to 1 month. The physicochemical properties of the PCL, PGO, and PGOD scaffolds were characterized by various analytical techniques. The biological response of these scaffolds was studied for adherence, proliferation, and osteogenic differentiation of seeded rabbit adipose-derived stem cells (ASCs) from DNA assays, alkaline phosphatase (ALP) production, calcium quantification, osteogenic gene expression, and immunofluorescence staining of osteogenic marker proteins. The PGOD scaffold was demonstrated to be the best scaffold for maintaining cell viability, cell proliferation, and osteogenic differentiation of ASCs in vitro. In vivo biocompatibility of PGOD was confirmed from subcutaneous implantation in nude mice where ASC-seeded PGOD can form ectopic bones, demonstrated by microcomputed tomography (micro-CT) analysis and immunofluorescence staining. Furthermore, implantation of PGOD/ASCs constructs into critical-sized cranial bone defects in rabbits form tissue-engineered bones at the defect site, observed using micro-CT and histological analysis.
我们制备了用于骨组织工程的三维（3D）打印聚己内酯（PCL）和 PCL/氧化石墨烯（GO）（PGO）支架。将抗炎和促成骨药物地塞米松（DEX）吸附到 GO 上，并成功地通过 3D 打印的 PGO/DEX（PGOD）支架实现了药物输送，DEX 从支架中的持续释放长达 1 个月。通过各种分析技术对 PCL、PGO 和 PGOD 支架的物理化学性质进行了表征。通过 DNA 分析、碱性磷酸酶（ALP）产生、钙定量、成骨基因表达和成骨标记蛋白的免疫荧光染色，研究了这些支架对种子兔脂肪来源干细胞（ASCs）黏附、增殖和成骨分化的生物学反应。PGOD 支架被证明是体外维持细胞活力、细胞增殖和成骨分化的最佳支架。通过裸鼠皮下植入证实了 PGOD 的体内生物相容性，在裸鼠皮下植入 PGOD 后，ASCs 可以形成异位骨，通过微计算机断层扫描（micro-CT）分析和免疫荧光染色证实了这一点。此外，将 PGOD/ASCs 构建体植入兔颅骨临界尺寸缺损中，在缺损部位形成组织工程骨，通过 micro-CT 和组织学分析观察到这一点。
