Abstract
One of the key challenges in engineering three-dimensional tissue constructs is the development of a mature microvascular network capable of supplying sufficient oxygen and nutrients to the tissue. Recent angiogenic therapeutic strategies have focused on vascularization of the constructed tissue, and its integration in vitro; these strategies typically combine regenerative cells, growth factors (GFs) with custom-designed biomaterials. However, the field needs to progress in the clinical translation of tissue engineering strategies. The article first presents a detailed description of the steps in neovascularization and the roles of extracellular matrix elements such as GFs in angiogenesis. It then delves into decellularization, cell, and GF-based strategies employed thus far for therapeutic angiogenesis, with a particularly detailed examination of different methods by which GFs are delivered in biomaterial scaffolds. Finally, interdisciplinary approaches involving advancement in biomaterials science and current state of technological development in fabrication techniques are critically evaluated, and a list of remaining challenges is presented that need to be solved for successful translation to the clinics.
Highlights
Cardiovascular disease is one of the major causes of mortality, accounting for approximately 30% of adult fatalities in developed countries.[1]
It delves into decellularization, cell, and growth factors (GFs)-based strategies employed far for therapeutic angiogenesis, with a detailed examination of different methods by which GFs are delivered in biomaterial scaffolds
When vascular endothelial growth factor (VEGF) was encapsulated in hydrophobic degradable PLGA microspheres prior to fabrication into PLGA scaffolds, this approach led to prolonged and sustained GF release, and higher local angiogenesis in vitro and in vivo compared to VEGF that was directly incorporated into PLGA scaffolds.[122]
Summary
Cardiovascular disease is one of the major causes of mortality, accounting for approximately 30% of adult fatalities in developed countries.[1]. Regenerative medicine aims to circumvent issues associated with organ transplants such as graft-vs-host disease (GvHD) and organ shortage.[3] Several avascular tissues, such as cartilage, bladder, and skin, have already been constructed successfully and been used in clinics.[4,5,6] tissue engineering strategies for larger vascularized organs and thick tissues have far proven limited, due to the lack of standardized protocols for generating a robust microvascular network with a mean diffusion distance of 150–200 lm, a critical diffusion limit This diffusion range is critical for sufficient nutrient and gas exchange in more complex tissues and organs such as liver, heart, muscle, and bone.[7] Therapeutic angiogenesis aims to address this issue by enhancing the formation of new blood vessels (neovascularization) in engineered tissues. Combination of important parameters approach is required to utilize tissue engineering techniques (cells, decellularized tissue, and GFs) and inter-disciplinary systems (functionalized-biomaterials and fabrication techniques) together to develop a successful system for clinical translation of engineered tissues/organs (Fig. 1)
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