Special Issue: Tissue Engineering Review Bioactive Glasses: Sprouting Angiogenesis in Tissue Engineering Saeid Kargozar, 1,9 Francesco Baino, 2,9 Sepideh Hamzehlou, 3,4 Robert G. Hill, 5, * and Masoud Mozafari 6,7,8, * The biggest strategic challenge for tissue engineering is the development of efficient vascularized networks in engineered tissues and organs. Bioactive glasses (BGs) are potent biomaterials for inducing angiogenesis in hard and soft tissue engineering applications. Because tissue-healing processes strongly depend on angiogenesis, recent interest in BGs has increased dra- matically. BGs with improved angiogenetic properties can be developed by adding a range of metallic ions (e.g., Cu 2+ , Co 2+ ) into their structure, but further development of BGs with improved angiogenic activity is required, and many crucial questions remain to be answered. We introduce here the salient fea- tures, the hurdles that must be overcome, and the hopes and constraints for the development of this approach. Importance of BGs in Tissue Engineering Bioactive glasses (BGs; see Glossary) have gained much attention in biomedical science owing to their ability to enhance osteogenesis and angiogenesis [1]. BGs were first intro- duced by Hench and coworkers in the late 1960s [2]. 45S5 Bioglass 1 , composed of a quaternary SiO 2 –CaO–Na 2 O–P 2 O 5 oxide system, was the first man-made inorganic material that was able to bond to living bone and create a stable and tightly bonded interface [3]. By mixing different percentages of these four oxides, several types of BGs have been devel- oped to improve their inherent properties; other oxides can also be added to impart specific therapeutic actions [4] (Box 1 and Table 1). The term ‘bioactivity’ in the context of these glasses traditionally refers to the formation of a hydroxycarbonated apatite (HCA) layer on the glass surface [5] upon contact with solutions mimicking human plasma such as Kokubo’s simulated body fluid (SBF) [6]. The bioactivity of the glasses is crucial to allow bonding to the bone tissue, which expedites bone repair process. Glass bioactivity depends on both composition (a maximum SiO 2 content of 60 mol% is recommended for melt-derived BGs with a specific surface area below 1 m 2 /g) and texture (BGs with 90 mol% of SiO 2 may be highly bioactive if they are produced by a sol-gel method leading to a specific surface area above 100 m 2 /g) [7]. In the field of tissue engineering and regenerative medicine, BGs have been extensively used for hard tissue engineering applications [8] because BGs satisfy three crucial require- ments for optimal bone regeneration: osteoconductivity, osteoinductivity, and osteointe- grativity [9]. It has been previously proposed that the ionic dissolution products released from BGs are the main determinant of the overexpression of genes involved in osteogenesis and angiogenesis that facilitate bone repair (Figure 1 and Table 2). BGs are already commonly used in clinical settings, for example as bone fillers for cavity defects that have been surgically created due to cyst and bone cancer removal [10]. BGs have been introduced to the market in various shapes and sizes, and it has been estimated that more than 1.5 million patients worldwide were Highlights The most successful tissue engineer- ing strategies rely on the formation of vascular networks in newly developed tissues and organs to supply nutrients and oxygen. A series of elements can be incorpo- rated into the structure of BGs that induce specific characteristics for tis- sue engineering applications. Newly developed BGs are able to pro- mote angiogenic activities in hard and soft tissue engineering applications through the release of specific ions. This class of biomaterials offers new sug- gestions for overcoming the challenges associated with neovascularization within engineered tissue constructs. 1 Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 2 Institute of Materials Physics and Engineering, Department of Applied Science and Technology (DISAT), Politecnico di Torino, Torino, Italy 3 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 4 Medical Genetics Network (MeGeNe), Universal Scientific Education and Research Network (USERN), Tehran, Iran 5 Unit of Dental Physical Sciences, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Mile End Road, London E1 4NS, UK 6 Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), PO Box 14155-4777, Tehran, Iran 430 Trends in Biotechnology, April 2018, Vol. 36, No. 4 https://doi.org/10.1016/j.tibtech.2017.12.003 © 2017 Elsevier Ltd. All rights reserved.