Functionalized 3D Hydroxyapatite Scaffold by Fusion Peptides-Mediated Small Extracellular Vesicles of Stem Cells for Bone Tissue Regeneration

Abstract

3D printing technology offers extensive applications in tissue engineering and regenerative medicine (TERM) because it can create a threedimensional porous structure with acceptable porosity and fine mechanical qualities that can mimic natural bone. Hydroxyapatite (HA) is commonly used as a bone repair material due to its excellent biocompatibility and osteoconductivity. Small extracellular vesicles (sEVs) derived from bone marrow mesenchymal stem cells (BMSCs) can regulate bone metabolism and stimulate the osteogenic differentiation of stem cells. This study has designed a functionalized bone regeneration scaffold (3D H-P-sEVs) by combining the biological activity of BMSCs-sEVs and the 3D-HA scaffold to improve bone regeneration. The scaffold utilizes the targeting of fusion peptides to increase the loading efficiency of sEVs. The composition, structure, mechanical properties, and in vitro degradation performance of the 3D H-P-sEVs scaffolds were examined. The composite scaffold demonstrated good biocompatibility, substantially increased the expression of osteogenic-related genes and proteins, and had a satisfactory bone integration effect in the critical skull defect model of rats. In conclusion, the combination of EVs and 3D-HA scaffold via fusion peptide provides an innovative composite scaffold for bone regeneration and repair, improving osteogenic performance.

Biomimetic Mineralized 3D-Printed Polycaprolactone Scaffold Induced by Self-Adaptive Nanotopology to Accelerate Bone Regeneration

“…Large bone defects resulting from trauma, degenerative diseases, tumors, etc. have long been a vital clinical threat to human health. , Despite their widespread use, autologous and allogeneic bone grafts suffer from drawbacks, such as sacrificial bone donor sites, insufficient supply, and other surgical complications. − Three-dimensional (3D) printing, also known as additive manufacturing, is an innovative technique for boosting the development of bone tissue engineering, − because it can meet the clinical needs for personalized design and spatial porous constructs. , Among the available material choices, biodegradable polymers are identified as a preferred candidate due to their excellent biocompatibility, suitable mechanical properties, and good processability. , Numerous clinically approved biodegradable polymers, such as polycaprolactone (PCL), poly­(lactic acid) (PLA), and poly­(lactides- co -glycolides) (PLGA), etc., have been employed as the matrices to produce 3D-printed scaffolds. ,− Unfortunately, the bioinert nature of these biodegradable polymers results in insufficient biofunctions, hindering cellular activities and bone regeneration. , Thus, endowing 3D-printed scaffolds with osteoconductivity and osteogenesis is highly required to ensure their orthopedic applications.…”

Shear Flow-Assembled Janus Membrane with Bifunctional Osteogenic and Antibacterial Effects for Guided Bone Regeneration

“…Bone repair, a complex multifactorial process, is crucial for skeletal system health. − Guided bone regeneration (GBR) membranes that reside at the interface between the bone and surrounding soft tissues have attracted increasing attention in bone repair and regeneration. , GBR membranes can serve as a barrier to prevent the invasion of soft tissue cells into the bone defect while promoting osteogenic differentiation. − Recent research efforts about GBR membranes have focused on the enhancement of osteogenic differentiation and antibacterial effects. For instance, Bottino and collaborators doped β-tricalcium phosphate to fabricate a GBR membrane with a uniform porous network, which increased cell attachment, proliferation, mineralization, and osteogenic gene expression .…”