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Type 1 diabetic patients with severe hypoglycemia unawareness have benefitted from cellular therapies, such as pancreas or islet transplantation; however, donor shortage and the need for immunosuppression limits widespread clinical application. We previously developed an intravascular bioartificial pancreas (iBAP) using silicon nanopore membranes (SNM) for immunoprotection. To ensure ample nutrient delivery, the iBAP will need a cell scaffold with high hydraulic permeability to provide mechanical support and maintain islet viability and function. Here, we examine the feasibility of superporous agarose (SPA) as a potential cell scaffold in the iBAP. SPA exhibits 66-fold greater hydraulic permeability than the SNM along with a short (<10 μm) diffusion distance to the nearest islet. SPA also supports short-term functionality of both encapsulated human islets and stem-cell-derived enriched β-clusters in a convection-based system, demonstrated by high viability (>95%) and biphasic insulin responses to dynamic glucose stimulus. These findings suggest that the SPA scaffold will not limit nutrient delivery in a convection-based bioartificial pancreas and merits continued investigation., (© 2021 Wiley Periodicals LLC.)

Type 1 diabetes (T1D) is an autoimmune disorder in which the body's own immune system selectively attacks beta cells within pancreatic islets resulting in insufficient insulin production and loss of the ability to regulate blood glucose (BG) levels. Currently, the standard of care consists of BG level monitoring and insulin administration, which are essential to avoid the consequences of dysglycemia and long-term complications. Although recent advances in continuous glucose monitoring and automated insulin delivery systems have resulted in improved clinical outcomes for users, nearly 80% of people with T1D fail to achieve their target hemoglobin A1c (HbA1c) levels defined by the American Diabetes Association. Intraportal islet transplantation into immunosuppressed individuals with T1D suffering from impaired awareness of hypoglycemia has resulted in lower HbA1c, elimination of severe hypoglycemic events, and insulin independence, demonstrating the unique potential of beta cell replacement therapy (BCRT) in providing optimal glycemic control and a functional cure for T1D. BCRTs need to maximize cell engraftment, long-term survival, and function in the absence of immunosuppression to provide meaningful clinical outcomes to all people living with T1D. One innovative technology that could enable widespread translation of this approach into the clinic is three-dimensional (3D) bioprinting. Herein, we review how bioprinting could facilitate translation of BCRTs as well as the current and forthcoming techniques used for bioprinting of a BCRT product. We discuss the strengths and weaknesses of 3D bioprinting in this context in addition to the road ahead for the development of BCRTs. Impact statement Significant research developments in beta cell replacement therapies show its promise in providing a functional cure for type 1 diabetes (T1D); yet, their widespread clinical use has been difficult to achieve. This review provides a brief overview of the requirements for a beta cell replacement product followed by a discussion on both the promise and limitations of three-dimensional bioprinting in facilitating the fabrication of such products to enable translation into the clinic. Advancements in this area could be a key component to unlocking the safety and effectiveness of beta cell therapy for T1D.

Mitigation of the foreign body response (FBR) and successful tissue integration are essential to ensuring the longevity of implanted devices and biomaterials. The use of porous materials and coatings has been shown to have an impact, as the textured surfaces can mediate macrophage interactions with the implant and influence the FBR, and the pores can provide space for vascularization and tissue integration. In this study, we use a new class of implantable porous biomaterials templated from bicontinuous interfacially jammed emulsion gels (bijels), which offer a fully percolating, non-constricting porous network with a uniform pore diameter on the order of tens of micrometers, and surfaces with consistent curvature. We demonstrate that these unique morphological features, inherent to bijel-templated materials (BTMs), can enhance tissue integration and vascularization, and reduce the FBR. Cylindrical polyethylene glycol diacrylate (PEGDA) BTMs, along with PEGDA particle-templated materials (PTMs), and non-templated materials (NTMs), were implanted into the subcutaneous space of athymic nude mice. After 28 days, implants were retrieved and analyzed via histological techniques. Within BTMs, blood vessels of increased size and depth, changes in collagen deposition, and increased presence of pro-healing macrophages were observed compared to that of PTM and NTM implants. Bijel templating offers a new route to biomaterials that can improve the function and longevity of implantable devices. STATEMENT OF SIGNIFICANCE: All implanted biomaterials are subject to the foreign body response (FBR) which can have a detrimental effect on their efficacy. Altering the surface chemistry can decrease the FBR by limiting the amount of proteins adsorbed to the implant. This effect can be enhanced by including pores in the biomaterial to allow new tissue growth as the implant becomes integrated in the body. Here, we introduce a new class of self-assembled biomaterials comprising a fully penetrating, non-constricting pore phase with hyperbolic (saddle) surfaces for enhanced tissue integration. These unique morphological characteristics result in dense blood vessel formation and favorable tissue response properties demonstrated in a four-week implantation study., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Success of cell therapy in avascular sites will depend on providing sufficient blood supply to transplanted tissues. A popular strategy of providing blood supply is to embed cells within a functionalized hydrogel implanted within the host to stimulate neovascularization. However, hydrogel systems are not always amenable for removal post-transplantation; thus, it may be advantageous to implant a device that contains cells while also providing access to the circulation so retrieval is possible. Here we investigate one instance of providing access to a vessel network, a thin sheet with through-cut slits, and determine if it can be vascularized from autologous materials. We compared the effect of slit width on vascularization of a thin sheet following subcutaneous implantation into an animal model. Polydimethylsiloxane sheets with varying slit widths (approximately 150, 300, 500, or 1500 µm) were fabricated from three-dimensional printed molds. Subcutaneous implantation of sheets in immunodeficient mice revealed that smaller slit widths have evidence of angiogenesis and new tissue growth, while larger slit widths contain native mature tissue squeezing into the space. Our results show that engineered slit sheets may provide a simple approach to cell transplantation by providing a prevascularized and innervated environment., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.