Transcriptome Analysis Revealed the Symbiosis Niche of 3D Scaffolds to Accelerate Bone Defect Healing

Abstract

Three dimension (3D) printed scaffolds have been shown to be superior in promoting tissue repair, but the cell-level specific regulatory network activated by 3D printing scaffolds with different material components to form a symbiosis niche have not been systematically revealed. Here, three typical 3D printed scaffolds, including natural polymer hydrogel (gelatin-methacryloyl, GelMA), synthetic polymer material (polycaprolactone, PCL), and bioceramic (𝜷-tricalcium phosphate, 𝜷-TCP), are fabricated to explore the regulating effect of the symbiotic microenvironment during bone healing. Enrichment analysis show that hydrogel promotes tissue regeneration and reconstruction by improving blood vessel generation by enhancing oxygen transport and red blood cell development. The PCL scaffold regulates cell proliferation and differentiation by promoting cellular senescence, cell cycle and deoxyribonucleic acid (DNA) replication pathways, accelerating the process of endochondral ossification, and the formation of callus. The 𝜷-TCP scaffold can specifically enhance the expression of osteoclast differentiation and extracellular space pathway genes to promote the differentiation of osteoclasts and promote the process of bone remodeling. In these processes, specific biomaterial properties can be used to guide cell behavior and regulate molecular network in the symbiotic microenvironment to reduce the barriers of regeneration and repair.

3D bioprinting of in situ vascularized tissue engineered bone for repairing large segmental bone defects

“…However, although 3D-printed scaffolds have been shown to be superior in promoting bone defect repair, the cell-level specific regulatory network had not yet been revealed, limiting their further application. In recent years, RNA-sequencing analysis has been developed as an effective analytical method and is widely used in biology and medicine [ 52 , 53 ]. In this study, 3D bioprinting of an in situ vascularized scaffold was performed, and RNA-sequencing analysis was used to explore the regulatory effect on both BMSCs and RAOECs compared with that for a control group.…”

Bioinspired sandwich-like hybrid surface functionalized scaffold capable of regulating osteogenesis, angiogenesis, and osteoclastogenesis for robust bone regeneration

“…To achieve effective bone repair, bioactive scaffolds used for bone regeneration should be nontoxic or slightly toxic and exhibit good cytocompatibility, which is a fundamental prerequisite in bone regeneration applications [ 39 ]. In this study, MC3T3-E1 cells were selected as the model cells due to their stable performance and good experimental reproducibility and are widely used in cytotoxicity evaluation, osteoblastic differentiation, osteoblastic mechanisms, and mineralization in vitro [ 6 , 40 ].…”

Construction of biomimetic cell-sheet-engineered periosteum with a double cell sheet to repair calvarial defects of rats

“…Bone defects caused by various aetiologies are common clinical problems that impose huge burden on society and severely affect patients' quality of life [ 46 ]. Over the past two decades, the rapid development of tissue engineering has brought new direction for bone regeneration.…”