Scalable and Uniform Fabrication of Dexamethasone-Eluting Depot-Engineered Stem Cell Spheroids as a Microtissue Construct to Target Bone Regeneration

Abstract

Potentiation of stem cell potency is critical for successful tissue engineering, especially for bone regeneration. Three-dimensional cell culture and bioactive molecule co-delivery with cells have been proposed to achieve this effect. Here, we provide a uniform and scalable fabrication of osteogenic microtissue constructs of mesenchymal stem cell (MSC) spheroids surfaceengineered with dexamethasone-releasing polydopamine-coated microparticles (PD-DEXA/MPs) to target bone regeneration. The microparticle conjugation process was rapid and cell-friendly and did not affect the cell viability or key functionalities. The incorporation of DEXA in the conjugated system significantly enhanced the osteogenic differentiation of MSC spheroids, as evidenced by upregulating osteogenic gene expression and intense alkaline phosphatase and alizarin red S staining. In addition, the migration of MSCs from spheroids was tested on a biocompatible macroporous fibrin scaffold (MFS). The result showed that PD-DEXA/MPs were stably anchored on MSCs during cell migration over time. Finally, the implantation of PD-DEXA/MP-conjugated spheroid-loaded MFS into a calvarial defect in a mouse model showed substantial bone regeneration. In conclusion, the uniform fabrication of microtissue constructs containing MSC spheroids with drug depots shows a potential to improve the performance of MSCs in tissue engineering.

Injectable Nano‐Micro Composites with Anti‐bacterial and Osteogenic Capabilities for Minimally Invasive Treatment of Osteomyelitis

“…We further utilized alkaline phosphatase (ALP) staining to detect ALP expression. [ 59 , 60 ] The results of ALP staining after 7 days of induction culture are shown in Figure 5f . The CaP@MS and CaP@MS‐Oligo‐Van groups exhibited more blue nodules and a darker color.…”