Engineered Vasculature for Cancer Research and Regenerative Medicine.

Engineered human tissues created by three-dimensional cell culture of human cells in a hydrogel are becoming emerging model systems for cancer drug discovery and regenerative medicine. Complex functional engineered tissues can also assist in the regeneration, repair, or replacement of human tissues. However, one of the main hurdles for tissue engineering, three-dimensional cell culture, and regenerative medicine is the capability of delivering nutrients and oxygen to cells through the vasculatures. Several studies have investigated different strategies to create a functional vascular system in engineered tissues and organ-on-a-chips. Engineered vasculatures have been used for the studies of angiogenesis, vasculogenesis, as well as drug and cell transports across the endothelium. Moreover, vascular engineering allows the creation of large functional vascular conduits for regenerative medicine purposes. However, there are still many challenges in the creation of vascularized tissue constructs and their biological applications. This review will summarize the latest efforts to create vasculatures and vascularized tissues for cancer research and regenerative medicine.

Vascularized adipose tissue engineering: moving towards soft tissue reconstruction.

Soft tissue defects are a common clinical challenge mostly caused by trauma, congenital anomalies and oncological surgery. Current soft tissue reconstruction options include synthetic materials (fillers and implants) and autologous adipose tissue transplantation through flap surgery and/or lipotransfer. Both reconstructive options hold important disadvantages to which vascularized adipose tissue engineering (VATE) strategies could offer solutions. In this review, we first summarized pivotal characteristics of functional adipose tissue such as the structure, function, cell types, development and extracellular matrix (ECM). Next, we discussed relevant cell sources and how they are applied in different state-of-the-art VATE techniques. Herein, biomaterial scaffolds and hydrogels, ECMs, spheroids, organoids, cell sheets, three dimensional printing and microfluidics are overviewed. Also, we included extracellular vesicles and emphasized their potential role in VATE. Lastly, current challenges and future perspectives in VATE are pointed out to help to pave the road towards clinical applications.

High-throughput fabrication of vascularized adipose microtissues for 3D bioprinting.

For patients with soft tissue defects, repair with autologous in vitro engineered adipose tissue could be a promising alternative to current surgical therapies. A volume-persistent engineered adipose tissue construct under in vivo conditions can only be achieved by early vascularization after transplantation. The combination of 3D bioprinting technology with self-assembling microvascularized units as building blocks can potentially answer the need for a microvascular network. In the present study, co-culture spheroids combining adipose-derived stem cells (ASC) and human umbilical vein endothelial cells (HUVEC) were created with an ideal geometry for bioprinting. When applying the favourable seeding technique and condition, compact viable spheroids were obtained, demonstrating high adipogenic differentiation and capillary-like network formation after 7 and 14 days of culture, as shown by live/dead analysis, immunohistochemistry and RT-qPCR. Moreover, we were able to successfully 3D bioprint the encapsulated spheroids, resulting in compact viable spheroids presenting capillary-like structures, lipid droplets and spheroid outgrowth after 14 days of culture. This is the first study that generates viable high-throughput (pre-)vascularized adipose microtissues as building blocks for bioprinting applications using a novel ASC/HUVEC co-culture spheroid model, which enables both adipogenic differentiation while simultaneously supporting the formation of prevascular-like structures within engineered tissues in vitro.