GelMA Hydrogel Reinforced with 3D Printed PEGT/PBT Scaffolds for Supporting Epigenetically-Activated Human Bone Marrow Stromal Cells for Bone Repair.
Kenny ManCesar AlcalaNaveen V MekhileriKhoon S LimLin-Hua JiangTim B F WoodfieldXuebin B YangPublished in: Journal of functional biomaterials (2022)
Epigenetic approaches using the histone deacetylase 2 and 3 inhibitor-MI192 have been reported to accelerate stem cells to form mineralised tissues. Gelatine methacryloyl (GelMA) hydrogels provide a favourable microenvironment to facilitate cell delivery and support tissue formation. However, their application for bone repair is limited due to their low mechanical strength. This study aimed to investigate a GelMA hydrogel reinforced with a 3D printed scaffold to support MI192-induced human bone marrow stromal cells (hBMSCs) for bone formation. Cell culture: The GelMA (5 wt%) hydrogel supported the proliferation of MI192-pre-treated hBMSCs. MI192-pre-treated hBMSCs within the GelMA in osteogenic culture significantly increased alkaline phosphatase activity ( p ≤ 0.001) compared to control. Histology: The MI192-pre-treated group enhanced osteoblast-related extracellular matrix deposition and mineralisation ( p ≤ 0.001) compared to control. Mechanical testing: GelMA hydrogels reinforced with 3D printed poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) scaffolds exhibited a 1000-fold increase in the compressive modulus compared to the GelMA alone. MI192-pre-treated hBMSCs within the GelMA-PEGT/PBT constructs significantly enhanced extracellular matrix collagen production and mineralisation compared to control ( p ≤ 0.001). These findings demonstrate that the GelMA-PEGT/PBT construct provides enhanced mechanical strength and facilitates the delivery of epigenetically-activated MSCs for bone augmentation strategies.
Keyphrases
- tissue engineering
- extracellular matrix
- bone marrow
- stem cells
- mesenchymal stem cells
- drug delivery
- endothelial cells
- histone deacetylase
- bone mineral density
- wound healing
- hyaluronic acid
- gene expression
- soft tissue
- cell therapy
- bone regeneration
- dna methylation
- single cell
- signaling pathway
- umbilical cord
- induced pluripotent stem cells
- high glucose
- postmenopausal women
- drug induced
- long noncoding rna
- stress induced
- pluripotent stem cells