5 research outputs found
Preclinical evaluation of the safety and effectiveness of a new bioartificial cornea
Cross-linking agents are frequently used to restore corneal properties after decellularization, and it is especially important to select an appropriate method to avoid excessive cross-linking. In addition, how to promote wound healing and how to improve scar formation require further investigation. To ensure the safety and efficacy of animal-derived products, we designed bioartificial corneas (BACs) according to the criteria for Class III medical devices. Our BACs do not require cross-linking agents and increase mechanical strength via self-cross-linking of aldehyde-modified hyaluronic acid (AHA) and carboxymethyl chitosan (CMC) on the surface of decellularized porcine corneas (DPCs). The results showed that the BACs had good biocompatibility and transparency, and the modification enhanced their antibacterial and anti-inflammatory properties in vitro. Preclinical animal studies showed that the BACs can rapidly regenerate the epithelium and restore vision within a month. After 3 months, the BACs were gradually filled with epithelial, stromal, and neuronal cells, and after 6 months, their transparency and histology were almost normal. In addition, side effects such as corneal neovascularization, conjunctival hyperemia, and ciliary body hyperemia rarely occur in vivo. Therefore, these BACs show promise for clinical application for the treatment of infectious corneal ulcers and as a temporary covering for corneal perforations to achieve the more time
Construction of Antithrombotic Tissue-Engineered Blood Vessel <i>via</i> Reduced Graphene Oxide Based Dual-Enzyme Biomimetic Cascade
Thrombosis
is one of the biggest obstacles in the clinical application
of small-diameter tissue-engineered blood vessels (TEBVs). The implantation
of an unmodified TEBV will lead to platelet aggregation and further
activation of the coagulation cascade, in which the high concentration
of adenosine diphosphate (ADP) that is released by platelets plays
an important role. Inspired by the phenomenon that endothelial cells
continuously generate endogenous antiplatelet substances <i>via</i> enzymatic reactions, we designed a reduced graphene oxide (RGO)
based dual-enzyme biomimetic cascade to successively convert ADP into
adenosine monophosphate (AMP) and AMP into adenosine. We used RGO
as a support and bound apyrase and 5′-nucleotidase (5′-NT)
on the surface of RGO through covalent bonds, and then, we modified
the surface of the collagen-coated decellularized vascular matrix
with the RGO-enzyme complexes, in which RGO functions as a platform
with a large open surface area and minimal diffusion barriers for
substrates/products to integrate two catalytic systems for cascading
reactions. The experimental results demonstrate that the two enzymes
can synergistically catalyze procoagulant ADP into anticoagulant AMP
and adenosine successively under physiological conditions, thus reducing
the concentration of ADP. AMP and adenosine can weaken or even reverse
the platelet aggregation induced by ADP, thereby inhibiting thrombosis.
Adenosine can also accelerate the endothelialization of TEBVs by regulating
cellular energy metabolism and optimizing the microenvironment, thus
ensuring the antithrombotic function and patency of TEBVs even after
the RGO-enzyme complex loses its activity