The Role of Vasculature and Angiogenic Strategies in Bone Regeneration

The Role of Vasculature and Angiogenic Strategies in Bone Regeneration

26 January 2024 | Hye-Jeong Jang and Jeong-Kee Yoon
This review discusses the critical role of vasculature and angiogenic strategies in bone regeneration. Bone regeneration involves the formation of a vascular network that provides nutrients and oxygen, promoting osteogenesis. The review highlights recent advancements in bone tissue engineering, emphasizing the importance of angiogenesis in bone regeneration. It examines the role of angiogenesis in bone regeneration, including in vitro and in vivo applications that have achieved accelerated bone regeneration through angiogenesis. The review also identifies remaining challenges and outlines future directions for research in vascularized bone regeneration. Bone regeneration occurs spontaneously in response to bone injury, involving multiple factors such as growth factors, osteoblasts, osteoclasts, inflammatory cytokines, and the extracellular matrix. The process of bone regeneration is a dynamic and organized procedure that typically consists of three phases: the inflammatory phase, the bone production phase, and the bone remodeling phase. During the bone production phase, vascularization occurs, and MSCs differentiate into osteoprogenitor cells. The bone remodeling phase then restores the structural and mechanical properties of the bone. Conventional bone tissue engineering methods primarily rely on autologous or allogenic bone grafts, but these have limitations such as poor availability and donor site morbidity. Artificial bone substitutes made from synthetic materials have emerged as a viable alternative. These materials, such as metals, bioceramics, and biodegradable polymers, are designed to mimic natural bone in terms of mechanical and biological properties. Angiogenic strategies for bone regeneration include the delivery of angiogenic growth factors, such as VEGF and BMP-2, which promote the formation of new bone tissue and blood vessels. Cell delivery strategies involve the co-culturing of different cell types, such as endothelial cells and mesenchymal stem cells, to enhance osteogenesis and angiogenesis. Gene delivery methods involve the targeted delivery and expression of angiogenic or osteogenic genes within the defect site. Perfusable 3D vascular networks are crucial for bone regeneration, as they mimic the natural environment of bone tissue and support the growth of viable tissue constructs. Hydrogels inducing angiogenesis are used to create vascularized bone models that mimic the natural bone extracellular matrix. Extracellular vesicle (EV) delivery is another strategy that involves the use of EVs to promote angiogenesis and bone regeneration. Three-dimensional-bioprinted models enable the precise fabrication of bone tissue with integrated vascular networks. Other synthetic models, such as microfluidic vascularized bone models, are emerging as in vitro platforms for studying the interactions between bone cells and blood vessels. The review concludes that ongoing research into the development and application of angiogenesis in bone regeneration holds tremendous potential for advancing the relevant fields and establishing novel strategies for targeted and efficient therapeutic interventions.This review discusses the critical role of vasculature and angiogenic strategies in bone regeneration. Bone regeneration involves the formation of a vascular network that provides nutrients and oxygen, promoting osteogenesis. The review highlights recent advancements in bone tissue engineering, emphasizing the importance of angiogenesis in bone regeneration. It examines the role of angiogenesis in bone regeneration, including in vitro and in vivo applications that have achieved accelerated bone regeneration through angiogenesis. The review also identifies remaining challenges and outlines future directions for research in vascularized bone regeneration. Bone regeneration occurs spontaneously in response to bone injury, involving multiple factors such as growth factors, osteoblasts, osteoclasts, inflammatory cytokines, and the extracellular matrix. The process of bone regeneration is a dynamic and organized procedure that typically consists of three phases: the inflammatory phase, the bone production phase, and the bone remodeling phase. During the bone production phase, vascularization occurs, and MSCs differentiate into osteoprogenitor cells. The bone remodeling phase then restores the structural and mechanical properties of the bone. Conventional bone tissue engineering methods primarily rely on autologous or allogenic bone grafts, but these have limitations such as poor availability and donor site morbidity. Artificial bone substitutes made from synthetic materials have emerged as a viable alternative. These materials, such as metals, bioceramics, and biodegradable polymers, are designed to mimic natural bone in terms of mechanical and biological properties. Angiogenic strategies for bone regeneration include the delivery of angiogenic growth factors, such as VEGF and BMP-2, which promote the formation of new bone tissue and blood vessels. Cell delivery strategies involve the co-culturing of different cell types, such as endothelial cells and mesenchymal stem cells, to enhance osteogenesis and angiogenesis. Gene delivery methods involve the targeted delivery and expression of angiogenic or osteogenic genes within the defect site. Perfusable 3D vascular networks are crucial for bone regeneration, as they mimic the natural environment of bone tissue and support the growth of viable tissue constructs. Hydrogels inducing angiogenesis are used to create vascularized bone models that mimic the natural bone extracellular matrix. Extracellular vesicle (EV) delivery is another strategy that involves the use of EVs to promote angiogenesis and bone regeneration. Three-dimensional-bioprinted models enable the precise fabrication of bone tissue with integrated vascular networks. Other synthetic models, such as microfluidic vascularized bone models, are emerging as in vitro platforms for studying the interactions between bone cells and blood vessels. The review concludes that ongoing research into the development and application of angiogenesis in bone regeneration holds tremendous potential for advancing the relevant fields and establishing novel strategies for targeted and efficient therapeutic interventions.
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