A Bottom-Up Assembly Of Vascularized Bioartificial Constructs Using Ecm Based Microscale Modules

Tissue engineering aims to create functional biological tissues to treat diseases and damaged organs. A primary goal is to fabricate a 3D construct that can promote cell-cell interaction, extra cellular matrix (ECM) deposition and tissue level organization. Accomplishing these prerequisites with the currently available conventional scaffolds and fabrication techniques still remains a challenge. To reproduce the full functionality there is a need to engineer tissue constructs that mimic the innate architecture and complexity of natural tissues. The limited ability to vascularize and perfuse thick, cell-laden tissue constructs has hindered efforts to engineer complex tissues and organs, including liver, heart and kidney. The emerging field of modular tissue engineering aims to address this limitation by fabricating constructs from the bottom up, with the objective of recreating native tissue architecture and promoting extensive vascularization. Here, we report the elements of a simple yet efficient method for fabricating vascularized tissue constructs by fusing biodegradable microcapsules with tunable interior environments. Parenchymal cells of various types, (i.e. trophoblasts, vascular smooth muscle cells, hepatocytes) were suspended in glycosaminoglycan (GAG) solutions (4%/1.5% chondroitin sulfate/carboxymethyl cellulose, or 1.5 wt% hyaluronan) and encapsulated by forming chitosan-GAG polyelectrolyte complex membranes around droplets of the cell suspension. The interior capsule environment could be further tuned by blending collagen with or suspending microcarriers in the GAG solution. These capsule modules were seeded externally with vascular endothelial cells (VEC), and subsequently fused into tissue constructs possessing VEC-lined, inter-capsule channels. The microcapsules supported high density growth achieving clinically significant cell densities. Fusion of the endothelialized capsules generated 3D constructs with an embedded network of interconnected channels that enabled long-term perfusion in-vitro and accelerated neovascularization in-vivo. A prototype, engineered liver tissue, formed by fusion of hepatocyte-containing capsules exhibited urea synthesis rates and albumin synthesis rates comparable to standard collagen sandwich hepatocyte cultures. Our modular approach has the potential to allow rapid assembly of liver constructs with clinically significant cell densities, uniform cell distribution, and endothelialized, perfusable channels

Trends in Photopolymerizable Bioinks for 3D Bioprinting of Tumor Models

Three-dimensional (3D) bioprinting technologies involving photopolymerizable bioinks (PBs) have attracted enormous attention in recent times owing to their ability to recreate complex structures with high resolution, mechanical stability, and favorable printing conditions that are suited for encapsulating cells. 3D bioprinted tissue constructs involving PBs can offer better insights into the tumor microenvironment and offer platforms for drug screening to advance cancer research. These bioinks enable the incorporation of physiologically relevant cell densities, tissue-mimetic stiffness, and vascularized channels and biochemical gradients in the 3D tumor models, unlike conventional two-dimensional (2D) cultures or other 3D scaffold fabrication technologies. In this perspective, we present the emerging techniques of 3D bioprinting using PBs in the context of cancer research, with a specific focus on the efforts to recapitulate the complexity of the tumor microenvironment. We describe printing approaches and various PB formulations compatible with these techniques along with recent attempts to bioprint 3D tumor models for studying migration and metastasis, cell-cell interactions, cell-extracellular matrix interactions, and drug screening relevant to cancer. We discuss the limitations and identify unexplored opportunities in this field for clinical and commercial translation of these emerging technologies

Additive manufacturing of bioactive glass biomaterials

Tissue engineering (TE) and regenerative medicine have held great promises for the repair and regeneration of damaged tissues and organs. Additive manufacturing has recently appeared as a versatile technology in TE strategies that enables the production of objects through layered printing. By applying 3D printing and bioprinting, it is now possible to make tissue-engineered constructs according to desired thickness, shape, and size that resemble the native structure of lost tissues. Up to now, several organic and inorganic materials were used as raw materials for 3D printing; bioactive glasses (BGs) are among the most hopeful substances regarding their excellent properties (e.g., bioactivity and biocompatibility). In addition, the reported studies have confirmed that BG-reinforced constructs can improve osteogenic, angiogenic, and antibacterial activities. This review aims to provide an up-to-date report on the development of BG-containing raw biomaterials that are currently being employed for the fabrication of 3D printed scaffolds used in tissue regeneration applications with a focus on their advantages and remaining challenges

4D Printing for Vascular Tissue Engineering: Progress and Challenges

The hierarchical network of blood vessels comprises the larger vessels (veins and arteries), the smaller ones (venules and arterioles), and the thinnest capillaries. The proper functioning of most tissues in the body relies on vascularization, which is meant for the diffusion of gases, nutrients, and harmful waste. However, it is known that cell survival is compromised as the diffusion of oxygen is limited beyond 100–200 µm and damage can occur at any level of the complex system of the vascular network, as is the case in cardiovascular, musculoskeletal, and neurovascular diseases that recur and progress with age. These may prove fatal, hence the need for vascular tissue engineering (VTE) arises. VTE mainly focuses on the fabrication of vascular constructs using natural, synthetic material, or a combination of both using various techniques. The construct is expected to integrate and anastomose with the host vasculature. 4D bioprinting is an emerging field that allows the fabrication of hollow tubes employing different materials that respond to different stimuli. This review is a comprehensive summary of the major techniques employed in VTE and the recent technique of 4D bioprinting foreseen to revolutionize the field