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Modular tissue engineering approaches open up exciting perspectives for the biofabrication of vascularized tissues from the bottom-up, using micro-sized units such as spheroids as building blocks. While several techniques for 3D spheroid formation from multiple cell types have been reported, strategies to elicit the extra-spheroid assembly of complex vascularized tissues are still scarce. Here we describe an injectable approach to generate vascularized dermal tissue, as an example application, from spheroids combining fibroblasts and endothelial progenitors (OEC) in a xeno-free (XF) setting. Short-term cultured spheroids (1 day) were selected over mature spheroids (7 days), as they showed significantly higher angiogenic sprouting potential. Embedding spheroids in fibrin was crucial for triggering cell migration into the external milieu, while providing a 3D framework for in-gel extra-spheroid morphogenesis. Migrating fibroblasts proliferated and produced endogenous ECM forming a dense tissue, while OEC self-assembled into stable capillaries with lumen and basal lamina. Massive in vitro interconnection between sprouts from neighbouring spheroids rapidly settled an intricate vascular plexus. Upon injection into the chorioallantoic membrane of chick embryos, fibrin-entrapped pre-vascularized XF spheroids developed into a macrotissue with evident host vessel infiltration. After only 4 days, perfused chimeric capillaries with human cells were present in proximal areas, showing fast and functional inosculation between host and donor vessels. This method for generating dense vascularized tissue from injectable building blocks is clinically relevant and potentially useful for a range of applications., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Polycaprolactone (PCL) is widely used in tissue engineering due to its interesting properties, namely biocompatibility, biodegradability, elastic nature, availability, cost efficacy, and the approval of health authorities such as the American Food and Drug Administration (FDA). The PCL degradation rate is not the most adequate for specific applications such as skin regeneration due to the hydrophobic nature of bulk PCL. However, PCL electrospun fiber meshes, due to their low diameters resulting in high surface area, are expected to exhibit a fast degradation rate. In this work, in vitro and in vivo degradation studies were performed over 90 days to evaluate the potential of electrospun PCL as a wound dressing. Enzymatic and hydrolytic degradation studies in vitro, performed in a static medium, demonstrated the influence of lipase, which promoted a rate of degradation of 97% for PCL meshes. In an in vivo scenario, the degradation was slower, although the samples were not rejected, and were well-integrated in the surrounding tissues inside the subcutaneous pockets specifically created. [ABSTRACT FROM AUTHOR]