Decellularized PLGA-based scaffolds and their osteogenic potential with bone marrow stromal cells

Abstract

A cell-derived extracellular matrix (ECM) was naturally obtained and its effect on the induction of osteogenesis of bone marrow stromal cells (BMSCs) was investigated. Once porous composite scaffolds made of poly(Llactic-co-glycolic acid) (PLGA), hydroxyapatite (HA), and β-tricalcium phosphate (β-TCP) were fabricated, these scaffolds were seeded with fibroblasts or preosteoblasts and cultured in vitro. They were then subjected to decellularization, resulting in fibroblasts-decellularized scaffolds (FDS) or preosteoblasts-decellularized scaffolds (PDS). Both fibronectin and type I collagen were clearly detected from the immunofluorescent staining of FDS and PDS, respectively. When the rabbit BMSCs-loaded scaffolds were cultured in the osteogenic medium for 4 weeks, the osteogenic potential of FDS and PDS was much greater than the PLGA/HA/β-TCP (control), as identified by histological staining and the alkaline phosphatase (ALP) activity. Meanwhile, when BMSC-seeded FDS was implanted subcutaneously into the nude mice, the results also indicated more upregulated osteogenic differentiation of BMSCs in vivo compared to the control. This study suggests that the microenvironment created by cell-derived ECM can provide a favorable template in prompting the osteogenesis of BMSCs.

Cell-derived matrices for tissue engineering and regenerative medicine applications

“…Subcutaneous implants of polyesterurethane scaffolds coated with mineralized osMSC-derived ECM induced the ingrowth of host cells and the formation of a mineralized matrix that stained positive for bone sialoprotein (BSP), whereas no mineralization or BSP was found in the uncoated polymer scaffold explants 31 . Similarly, Hong et al demonstrated enhanced osteogenic differentiation of naïve MSCs implanted on PLGA/HA/β-TCP scaffolds coated with fibroblast-CDM using a subcutaneous ectopic bone formation model 28 . Explanted matrix-coated scaffolds had greater collagen and calcium deposition and ALP expression than uncoated scaffolds 28 .…”

“…Similarly, Hong et al demonstrated enhanced osteogenic differentiation of naïve MSCs implanted on PLGA/HA/β-TCP scaffolds coated with fibroblast-CDM using a subcutaneous ectopic bone formation model 28 . Explanted matrix-coated scaffolds had greater collagen and calcium deposition and ALP expression than uncoated scaffolds 28 . The increased osteogenic differentiation of implanted MSCs was attributed primarily to instructive cues present in the CDM, as the MSC were not treated with soluble exogenous osteogenic factors prior to implantation.…”

“…Decellularized matrices derived from fibroblasts and pre-osteoblasts yielded similar MSC osteogenic differentiation on composite poly(lactic-co-glycolic acid; PLGA)/hydroxyapatite(HA)/β-tricalcium(β-TCP) scaffolds 28 . The CDM-coated composite scaffolds contained fibronectin and collage type I, and stimulated increased ALP activity and mineralization when reseeded with MSC in osteogenic media, compared to uncoated PLGA/HA/β-TCP scaffolds 28 .…”

“…The CDM-coated composite scaffolds contained fibronectin and collage type I, and stimulated increased ALP activity and mineralization when reseeded with MSC in osteogenic media, compared to uncoated PLGA/HA/β-TCP scaffolds 28 . Decaris et al demonstrated that osteogenic CDM generated as 2D culture substrates could be coated onto a 3D scaffold, while retaining their capacity to modulate osteogenic differentiation 29, 30 .…”

Three-Dimensional Vascularized Lung Cancer-on-a-Chip with Lung Extracellular Matrix Hydrogels for In Vitro Screening

“…Decellularization involves the removal of cells, keeping intact the other ECM components in tissues or organs [15]. Decellularized ECM (dECM) produced by this technique has been used in tissue engineering applications because it mimics the natural tissue microenvironment by providing bioactive components, such as growth factors and cytokines [16][17][18][19][20]. dECM has also been used in various cancer studies as a scaffold to provide a microenvironment for the 3D culture of cancer cells.…”