Abstract
Tissue engineering has been shown to offer promising approaches for bone regeneration, mostly based on replacement with biomaterials that provide specific environments and support for bone growth. In this context, we previously showed that mesenchymal stem cells (MSCs) and their derivatives, such as conditioned medium (CM) and extracellular vesicles (EV), when seeded on collagen membranes (COL) or polylactide (PLA) biomaterials, are able to favor bone tissue regeneration, especially evidenced in animal model calvary defects. In the present study, we investigated whether the enrichment of a rat calvary defect site with CM, EVs and polyethylenimine (PEI)-engineered EVs could substantially modify the bone remodeling kinetics during defect healing, as these products were reported to favor bone regeneration. In particular, we focused the study, performed by synchrotron radiation-based high-resolution tomography, on the analysis of the bone mass density distribution. We proved that the enrichment of a defect site with CM, EVs and PEI-EVs substantially modifies, often accelerating, bone remodeling kinetics and the related mineralization process during defect healing. Moreover, different biomaterials (COL or PLA) in combination with stem cells of different origin (namely, human periodontal ligament stem cells-hPDLSCs and human gingival mesenchymal stem cells-hGMSCs) and their own CM, EVs and PEI-EVs products were shown to exhibit different mineralization kinetics.
Highlights
Mineralized bone is a fundamental connective tissue because it supports locomotion, protects the soft tissues and is the reserve of calcium and phosphate in the human body
We have shown that these mesenchymal stem cells (MSCs) and their derivatives, such as conditioned medium (CM) and extracellular vesicles (EV), when seeded on appropriate biomaterials, are able to regenerate bone tissues, especially in calvary defects [16,17,18,19,20]
The aim of this study was the investigation of the bone density distribution in-vivo, on rat calvaria defects, grafted with two alternative constructs: (a) collagen membranes (COL) scaffold seeded with human PDLSCs and hPDLSCs-derived CM or hPDLSCs-derived EVs or hPDLSCs-derived PEI-EVs; (b)
Summary
Mineralized bone is a fundamental connective tissue because it supports locomotion, protects the soft tissues and is the reserve of calcium and phosphate in the human body. It is highly remodeled thanks to a process that combines resorption due to osteoclasts and bone formation due to osteoblasts [1]. When large bone defects are present due to trauma or skeletal anomalies or when a disease causes an unbalanced regenerative process, as in the case of osteoporosis, bone regeneration is an important issue that requires specific treatments. In these cases, tissue engineering has been shown to offer promising approaches for bone regeneration, most of which are based on replacement with biomaterials that provide specific environments that promote bone formation. The ideal biomaterial should be biocompatible and safe, but should be osteoinductive and osteoconductive, improving cell viability, adhesion, proliferation and osteogenic differentiation [2,3].
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