About this Research Topic

Background

Tissue engineering aims at developing biological substitutes to replace traumatic, neoplastic or degenerative tissue loss, by the in vitro culture of appropriate progenitor cells with suitable material scaffolds to regenerate the function of physiological tissue. However, upon implantation in vivo, a major challenge for clinically relevant large‐size grafts is the maintenance of cell viability in the core of the scaffold, which critically depends on the rapid invasion of the construct by the host blood vessels. In fact, diffusion from the surrounding blood vascular bed only reaches the outer shell of the graft, resulting in cell death in the central core of the implants and limiting tissue ingrowth to the outer 1-2 millimeters. Furthermore, the presence of a functional vasculature also allows the recruitment of highly specialized cells, like circulating tissue progenitors or myeloid cells, which can contribute to tissue regeneration and remodeling. The regulation of vascular growth and tissue regeneration by immune cells is also an emerging area of significant interest. Finally, removal of interstitial fluid (extravasated cells, proteins, lipds) through uptake by lymphatic capillaries and return to the blood stream by larger lymphatic vessels represents one of the challenges in vascular engineering and regeneration.

Therefore, rapid vascularization is of vital importance for survival and function of tissue-engineered grafts of clinically relevant size and one of the major limiting factors towards their implementation for the treatment of patients. Oxygen and nutrient supply, as well as waste removal and control of interstitial fluid composition and oncotic pressure, are ensured by the formation of pervasive microcapillary networks derived from blood and lymphatic vascular endothelial cells that need to connect with the systemic arterio-venous circulation. Further, functional vascularization needs to be established within days of in vivo implantation to allow survival of progenitors and effective tissue formation.

Angiogenesis and lymphangiogenesis are complex and highly regulated processes. The design of rational therapeutic approaches stands to greatly benefit from a thorough understanding of the cellular and molecular mechanisms underlying the physiological growth and remodeling of vascular structures under therapeutic conditions.

Within this Research Topic, we envisage submissions on current in vitro and in vivo strategies for successful vascularization of artificial tissues, linking vascular biology principles to bio-inspired technological approaches and to translational aspects. Topics will include (but will not be limited to): 1) angiogenesis and lymphangiogenesis mechanisms and control of biological signals; 2) gene transfer for angiogenesis and lymphangiogenesis; 3) biomaterial-based control of vascularization, including de- and re-cellularized matrices; 4) pre-vascularization strategies, including co-culture systems of endothelial cells with other supporting cell types and surgical approaches.

Keywords: angiogenesis, tissue engineering, cell therapy, growth factors, gene therapy, extracellular matrix, biomaterials

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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