Bone Microenvironment‐Mimetic Scaffolds with Hierarchical Microstructure for Enhanced Vascularization and Bone Regeneration

Abstract

Microchannel networks within engineered 3D scaffold can allow nutrient exchange and rapid blood vessels formation. However, fabrication of a bone microenvironment‐mimicking scaffold with hierarchical micro/nanofibrous and microchannel structures is still a challenge. Herein, inspired by structural and functional cues of bone remodeling, a microchannel networks‐enriched nanofibrous scaffold by using 3D printing and thermally induced phase separation techniques, which can facilitate cells migration and nutrients transportation, is developed. The customizable vascular‐like structure of polycaprolactone within the nanofibrous gelatin‐silica scaffold is fabricated using 3D‐printed sacrificial templates, while dimethyloxalylglycine (DMOG)‐loaded mesoporous silica nanoparticles (MSNs) located on the scaffold surface and bone forming peptide‐1 (BFP)‐loaded MSNs embedded in the scaffold are implemented for sequential release of DMOG and BFP. The cell experiments show that dual‐drug delivery scaffold (DBM/GP) promotes angiogenesis by stimulating migration, tube formation, and angiogenesis‐related genes/protein expression of endothelial cells, and osteogenesis by promoting osteo‐related genes expression and mineral deposition of osteoblasts. Additionally, DBM/GP scaffold facilitates the angiogenic activity of osteoblasts by activating phosphatidylinositol 3‐kinase/protein kinase B/hypoxia inducible factor‐1α pathway. Furthermore, enhanced vascularization and bone regeneration of DBM/GP scaffold are demonstrated via subcutaneous and skull defect models. Overall, this study reveals that the bone microenvironment‐mimetic dual‐drug delivery scaffold provides a promising strategy for bone defects treatment.

Inhibition of Sympathetic Activation by Delivering Calcium Channel Blockers from a 3D Printed Scaffold to Promote Bone Defect Repair

“…[ 13 ] Therefore, RT‐qPCR and western blot were carried out to evaluate the effect of SGL‐NP@Eth scaffold on the osteogenic activities of BMSCs grown on the scaffold, and the effect of osteoclastic activity of BMMCs was also assessed. [ 51 ] Figure A–D shows the expression levels of osteogenic genes of BMSCs, including runt‐related transcription factor 2 (RUNX2), Osterix, OPN, and collagen type I (Col1a). The expressions levels of RUNX2 and Osterix were significantly increased in SGL‐NP@Eth (ISO (+)) and SGL (ISO (+)) groups compared to SG (ISO (+)) group at day 7.…”

Biomaterials to promote vascularization in tissue engineering organs and ischemic fibrotic diseases

“…59 Microchannel scaffolds loaded with osteogenic peptide-1 bone forming peptide can significantly stimulate vascular EC migration, tube formation, and angiogenesis-related gene/protein expression to promote angiogenesis (Figure 3A). 60 Cryodeposition modeling low-temperature deposition modeling-printed sponges containing MSCs significantly promoted vascularized bone regeneration (Figure 3B). 61 The porous structure of the microspheres facilitates cell adhesion and provides a large surface area for cell proliferation.…”

“…(A) Hollow polycaprolactone (PCL) scaffold with interconnected microchannel networks could promote angiogenesis and osteogenesis. Copyright permission from Ha et al 60 (B) Schematic illustration of highly interconnected porous structure to achieve vascularized bone regeneration. Copyright permission from Lian et al 61 (C) Microspheres and cell morphology observed under scanning electron microscope (SEM) for human umbilical vein endothelial cells (HUVECs) cultured on microspheres for 7 days.…”

Biomedical Applications of MXene‐Integrated Composites: Regenerative Medicine, Infection Therapy, Cancer Treatment, and Biosensing

“…[62,63] As an alternative, many scaffolds or bonesubstitute biomaterials have been developed to reconstruct the defects and regenerate bone tissues. [63,64] One of the key requirements of bone tissue engineering is the design and development of tissue engineering scaffolds that recapitulate important characteristics of bone to mimic native bone tissue function and therefore regenerate the damaged tissues. [65][66][67] In addition to the antibacterial and biocompatibility of Ti 3 C 2 MXene, they have Ca 2+ binding sites which promote osteogenesis.…”