3D-printed nano-hydroxyapatite/poly(lactic-co-glycolic acid) scaffolds with adipose-derived mesenchymal stem cells enhance bone regeneration in rat model of bone defects

Abstract

Three-dimensional (3D) printing has huge potential in the medical field, including bone tissue engineering scaffolds. In our study, the 3D-printed poly (lactic-co-glycolic acid) (PLGA)/nano-hydroxyapatite (HA) scaffolds carrying adipose-derived mesenchymal stem cells (ADMSCs) were constructed, and whether such scaffolds have therapeutic potential in bone defects was investigated. For in vitro assays, rat ADMSCs were implanted into blank cell wells (Blank) and PLGA/nHA and ADMSCs/PLGA/nHA scaffolds. The vitality and proliferation of ADMSCs were detected through calcein-AM/PI staining and CCK-8 assay to assess the biocompatibility of the scaffolds. ADMSCs in three groups were incubated in osteogenic induction medium, and ALP and ARS staining were performed after 7 days and 21 days, respectively. Runx2, Osterix, OCN, and OPN mRNA expression in ADMSCs was detected through RT-qPCR. For in vivo assays, rat models of radius defects were implanted by PLGA/nHA scaffolds or ADMSCs/PLGA/nHA scaffolds, and micro-CT scan analysis was conducted at week 12 after implantation. Bone marrow cell formation and Runx2 expression in rat radius tissues were evaluated through H&E and immunohistochemical staining, respectively. The results showed that ADMSCs/PLGA/nHA scaffolds provided transplanted cells with a stable carrier as well as maintained their activity and facilitated their proliferation. ADMSCs/PLGA/nHA promoted ADMSC osteogenic differentiation in vitro. Besides, the implantation of ADMSCs/PLGA/nHA scaffolds improved bone regeneration, enhanced bone marrow cell formation, and increased Runx2 expression in rat models of radius defects. Collectively, the 3D-printed ADMSCs/PLGA/nHA scaffolds effectively promote ADMSC osteogenic differentiation and exhibit significant bone repair effects, suggesting its therapeutical potential for bone defects.