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Polymeric nanofibrous scaffolds laden with cell-derived extracellular matrix for bone regeneration.

ABSTRACT: Bone tissue engineering aims to alleviate the shortage of available autograft material and the biological/mechanical incompatibility of allografts through fabrication of bioactive synthetic bone graft substitutes. However, these substitute grafting materials have insufficient biological potency that limits their clinical efficacy in regenerating large defects. Extracellular matrix, a natural tissue scaffold laden with biochemical and structural cues regulating cell adhesion and tissue morphogenesis, may be a versatile supplement that can extend its biological functionality to synthetic grafts. Embedding decellularized extracellular matrix (dECM) into synthetic polymers offers a promising strategy to enhance cellular response to synthetic materials, mitigate physical and mechanical limitations of dECMs, and improve clinical utility of synthetic bone grafts. Enriched with dECM biochemical cues, synthetic polymers can be readily fabricated into complex biocomposite grafts that mimic bone structure and stimulate endogenous cells to regenerate bone. In this study, cell-derived dECMs from osteoblast and endothelial cells were incorporated into polycaprolactone (PCL) solutions for electrospinning dual-layer nanofibrous scaffolds with osteogenic and vascular cues. The study examined the bioactivity of dECM scaffolds in osteoblast cultures for cell number, mineral deposits, and osteogenic markers, as well as regeneration of cortical bone defect in a rat femur. Scaffolds with osteoblast dECM had a significantly robust osteoblast proliferation, Alizarin Red staining/concentration, and osteopontin-positive extracellular deposits. Implanted scaffolds increased bone growth in femoral defects, and constructs with both osteogenic and vascular cues significantly improved cortical width. These findings demonstrate the potential to fabricate tailored biomimetic grafts with dECM cues and fibrous architecture for bone applications.

SUBMITTER: Junka R

PROVIDER: S-EPMC7292471 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Cell-derived extracellular matrix (ECM) has been employed as scaffolds for tissue engineering, creating a biomimetic microenvironment that provides physical, chemical and mechanical cues for cells and supports cell adhesion, proliferation, migration and differentiation by mimicking their in vivo microenvironment. Despite the enhanced bioactivity of cell-derived ECM, its application as a scaffold to regenerate hard tissues such as bone is still hampered by its insufficient mechanical properties. The combination of cell-derived ECM with synthetic biomaterials might result in an effective strategy to enhance scaffold mechanical properties and structural support. Electrospinning has been used in bone tissue engineering to fabricate fibrous and porous scaffolds, mimicking the hierarchical organized fibrillar structure and architecture found in the ECM. Although the structure of the scaffold might be similar to ECM architecture, most of these electrospun scaffolds have failed to achieve functionality due to a lack of bioactivity and osteoinductive factors. In this study, we developed bioactive cell-derived ECM electrospun polycaprolactone (PCL) scaffolds produced from ECM derived from human mesenchymal stem/stromal cells (MSC), human umbilical vein endothelial cells (HUVEC) and their combination based on the hypothesis that the cell-derived ECM incorporated into the PCL fibers would enhance the biofunctionality of the scaffold. The aims of this study were to fabricate and characterize cell-derived ECM electrospun PCL scaffolds and assess their ability to enhance osteogenic differentiation of MSCs, envisaging bone tissue engineering applications. Our findings demonstrate that all cell-derived ECM electrospun scaffolds promoted significant cell proliferation compared to PCL alone, while presenting similar physical/mechanical properties. Additionally, MSC:HUVEC-ECM electrospun scaffolds significantly enhanced osteogenic differentiation of MSCs as verified by increased ALP activity and osteogenic gene expression levels. To our knowledge, these results describe the first study suggesting that MSC:HUVEC-ECM might be developed as a biomimetic electrospun scaffold for bone tissue engineering applications.

Project description:Tissue engineering has become a promising therapeutic approach for bone regeneration. Nanofibrous scaffolds have attracted great interest mainly due to their structural similarity to natural extracellular matrix (ECM). Poly(lactide-co-?-caprolactone) (PLCL) has been successfully used in bone regeneration, but PLCL polymers are inert and lack natural cell recognition sites, and the surface of PLCL scaffold is hydrophobic. Silk fibroin (SF) is a kind of natural polymer with inherent bioactivity, and supports mesenchymal stem cell attachment, osteogenesis, and ECM deposition. Therefore, we fabricated hybrid nanofibrous scaffolds by adding different weight ratios of SF to PLCL in order to find a scaffold with improved properties for bone regeneration.Hybrid nanofibrous scaffolds were fabricated by blending different weight ratios of SF with PLCL. Human adipose-derived stem cells (hADSCs) were seeded on SF/PLCL nanofibrous scaffolds of various ratios for a systematic evaluation of cell adhesion, proliferation, cytotoxicity, and osteogenic differentiation; the efficacy of the composite of hADSCs and scaffolds in repairing critical-sized calvarial defects in rats was investigated.The SF/PLCL (50/50) scaffold exhibited favorable tensile strength, surface roughness, and hydrophilicity, which facilitated cell adhesion and proliferation. Moreover, the SF/PLCL (50/50) scaffold promoted the osteogenic differentiation of hADSCs by elevating the expression levels of osteogenic marker genes such as BSP, Ocn, Col1A1, and OPN and enhanced ECM mineralization. In vivo assays showed that SF/PLCL (50/50) scaffold improved the repair of the critical-sized calvarial defect in rats, resulting in increased bone volume, higher trabecular number, enhanced bone mineral density, and increased new bone areas, compared with the pure PLCL scaffold.The SF/PLCL (50/50) nanofibrous scaffold facilitated hADSC proliferation and osteogenic differentiation in vitro and further promoted new bone formation in vivo, suggesting that the SF/PLCL (50/50) nanofibrous scaffold holds great potential in bone tissue regeneration.

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Polymeric nanofibrous scaffolds laden with cell-derived extracellular matrix for bone regeneration.

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