Investigation on Adaptability and Applicability of Polymer-Mediated Cell Surface Engineering by Ligation with Transglutaminase.

Polymer-mediated cell surface engineering can be a powerful tool to modify the cell's biological behavior, but a simple ligation strategy must be identified. This manuscript assessed the use of transglutamination as a versatile and adaptable approach for cell surface engineering in various cellular models relevant to biomedical applications. This enzymatic approach was evaluated for its feasibility and potential for conjugating polymers to diverse cell surfaces and its biological effects.

Ex vivo enzymatic treatment converts blood type A donor lungs into universal blood type lungs.

Donor organ allocation is dependent on ABO matching, restricting the opportunity for some patients to receive a life-saving transplant. The enzymes FpGalNAc deacetylase and FpGalactosaminidase, used in combination, have been described to effectively convert group A (ABO-A) red blood cells (RBCs) to group O (ABO-O). Here, we study the safety and preclinical efficacy of using these enzymes to remove A antigen (A-Ag) from human donor lungs using ex vivo lung perfusion (EVLP).

Prevention of vascular-allograft rejection by protecting the endothelial glycocalyx with immunosuppressive polymers.

Systemic immunosuppression for the mitigation of immune rejection after organ transplantation causes adverse side effects and constrains the long-term benefits of the transplanted graft. Here we show that protecting the endothelial glycocalyx in vascular allografts via the enzymatic ligation of immunosuppressive glycopolymers under cold-storage conditions attenuates the acute and chronic rejection of the grafts after transplantation in the absence of systemic immunosuppression. In syngeneic and allogeneic mice that received kidney transplants, the steric and immunosuppressive properties of the ligated polymers largely protected the transplanted grafts from ischaemic reperfusion injury, and from immune-cell adhesion and thereby immunocytotoxicity.

Biomimetically Mineralized Alginate Nanocomposite Fibers for Bone Tissue Engineering: Mechanical Properties and in Vitro Cellular Interactions.

We report herein the structural and mechanical properties and in vitro cellular response of hydroxyapatite (HAp)/alginate nanocomposite fibrous scaffolds mimicking the mineralized collagen fibrils of bone tissue. The biomimetically "" nanocomposites, fabricated by electrospinning and in situ synthesis strategy, were compared with pure alginate nanofibers and micrometer-level HAp/alginate composite fibers. The tensile strength and elastic modulus of the nanocomposites increased by 79.

An enzymatic pathway in the human gut microbiome that converts A to universal O type blood.

Access to efficient enzymes that can convert A and B type red blood cells to 'universal' donor O would greatly increase the supply of blood for transfusions. Here we report the functional metagenomic screening of the human gut microbiome for enzymes that can remove the cognate A and B type sugar antigens. Among the genes encoded in our library of 19,500 expressed fosmids bearing gut bacterial DNA, we identify an enzyme pair from the obligate anaerobe Flavonifractor plautii that work in concert to efficiently convert the A antigen to the H antigen of O type blood, via a galactosamine intermediate.

Surface Engineering for Cell-Based Therapies: Techniques for Manipulating Mammalian Cell Surfaces.

The introduction of cell-based therapies has provided new and unique strategies to treat many diseases and disorders including the recent approval of CAR-T cell therapy for the leukemia. Cell surface engineering is a methodology in which the cell surface is tailored to modulate cellular function and interactions. In addition to genetic engineering of cell surface proteins, a wide array of robust, innovative and elegant approaches have been developed to selectively target the cell surface.

Novel grooved substrata stimulate macrophage fusion, CCL2 and MMP-9 secretion.

Rough surface topographies on implants attract macrophages but the influence of topography on macrophage fusion to produce multinucleated giant cells (MGC) and foreign body giant cells (FBGC) is unclear. Two rough novel grooved substrata, G1 and G2, fabricated by anisotropic etching of Silicon <110> crystals without the use of photolithographic patterning, and a control smooth surface (Pol) were produced and replicated in epoxy. The surfaces were compared for their effects on RAW264.