Effects of Metformin Delivery via Biomaterials on Bone and Dental Tissue Engineering

Abstract

Bone tissue engineering is a promising approach that uses seed-cell-scaffold drug delivery systems to reconstruct bone defects caused by trauma, tumors, or other diseases (e.g., periodontitis). Metformin, a widely used medication for type II diabetes, has the ability to enhance osteogenesis and angiogenesis by promoting cell migration and differentiation. Metformin promotes osteogenic differentiation, mineralization, and bone defect regeneration via activation of the AMP-activated kinase (AMPK) signaling pathway. Bone tissue engineering depends highly on vascular networks for adequate oxygen and nutrition supply. Metformin also enhances vascular differentiation via the AMPK/mechanistic target of the rapamycin kinase (mTOR)/NLR family pyrin domain containing the 3 (NLRP3) inflammasome signaling axis. This is the first review article on the effects of metformin on stem cells and bone tissue engineering. In this paper, we review the cutting-edge research on the effects of metformin on bone tissue engineering. This includes metformin delivery via tissue engineering scaffolds, metformin-induced enhancement of various types of stem cells, and metformin-induced promotion of osteogenesis, angiogenesis, and its regulatory pathways. In addition, the dental, craniofacial, and orthopedic applications of metformin in bone repair and regeneration are also discussed.

Interaction between apical periodontitis and systemic disease (Review)

“…Moreover, the imbalance of calcium homeostasis associated with insulin deficiency leads to bone loss ( 48 , 49 ). Metformin, a classical diabetic prescription drug, improves hyperglycemic conditions and enhances osteogenesis by regulating glucose metabolism, promoting cell migration and increasing angiogenesis ( 50 , 51 ). In addition, metformin could activate the proliferation and osteogenic differentiation of dental pulp and periodontal ligament stem cells, which serve an important role in the repair and mineralization of oral-associated bone defects ( 52 , 53 ).…”

3D Elastomeric Stent Functionalized with Antioxidative and Perivascular Tissue Regenerative Activities Ameliorated PVT Deprivation‐Induced Vein Graft Failure

“…It was known that metformin promoted tissue regeneration such as osteogenesis, angiogenesis, and periodontium regeneration. [46][47][48] What is more, administering metformin can activate and regulate the differentiation of adipose-derived stem cells. [49] In this study, we found the adventitia and PVAT was well regenerated around MET 3D-stent vein grafts.…”

Ag2O‐TiO2‐NTs enhance osteogenic activity in vitro by modulating TNF‐α/β‐catenin signaling in bone marrow‐derived mesenchymal stem cells

“…Bones are the basic structures that support the body, act as levers for the muscles to achieve the body movement, and protect internal organs (Sun et al., 2022). However, the incidence of bone‐related disorders, including fractures, osteoporosis, and intervertebral disc diseases continues to increase with advancing age (Zhu et al., 2022). Studies have shown that more than 200,000 individuals worldwide are affected by trauma‐ or disease‐induced bone tissue loss each year.…”