Decellularized kidney extracellular matrix-based hydrogels for renal tissue engineering.

Kidney regeneration is hindered by the limited pool of intrinsic reparative cells. Advanced therapies targeting renal regeneration have the potential to alleviate the clinical and financial burdens associated with kidney disease. Delivery systems for cells, extracellular vesicles, or growth factors aimed at enhancing regeneration can benefit from vehicles enabling targeted delivery and controlled release. Hydrogels, optimized to carry biological cargo while promoting regeneration, have emerged as promising candidates for this purpose. This study aims to develop a hydrogel from decellularized kidney extracellular matrix (DKECM) and explore its biocompatibility as a biomaterial for renal regeneration. The resulting hydrogel crosslinks with temperature and exhibits a high concentration of extracellular matrix. The decellularization process efficiently removes detergent residues, yielding a pathogen-free biomaterial that is non-hemolytic and devoid of α-gal epitope. Upon interaction with macrophages, the hydrogel induces differentiation into both pro-inflammatory and anti-inflammatory phenotypes, suggesting an adequate balance to promote biomaterial functionality in vivo. Renal progenitor cells encapsulated in the DKECM hydrogel demonstrate higher viability and proliferation than in commercial collagen-I hydrogels, while also expressing tubular cells and podocyte markers in long-term culture. Overall, the injectable biomaterial derived from porcine DKECM is anticipated to elicit minimal host reaction while fostering progenitor cell bioactivity, offering a potential avenue for enhancing renal regeneration in clinical settings. STATEMENT OF SIGNIFICANCE: The quest to improve treatments for kidney disease is crucial, given the challenges faced by patients on dialysis or waiting for transplants. Exciting new therapies combining biomaterials with cells can revolutionize kidney repair. In this study, researchers created a hydrogel from pig kidney. This gel could be used to deliver cells and other substances that help in kidney regeneration. Despite coming from pigs, it's safe for use in humans, with no harmful substances and reduced risk of immune reactions. Importantly, it promotes a balanced healing response in the body. This research not only advances our knowledge of kidney repair but also offers hope for more effective treatments for kidney diseases.

Biomimetic Surface Topography from the Rubus fruticosus Leaf as a Guidance of Angiogenesis in Tissue Engineering Applications.

The promotion of angiogenesis is a fundamental step for efficient organ/tissue reconstitution and replacement. Thus, several strategies to promote vascularization of scaffolds were studied to satisfy this unsolved clinical need. The interface between cells and substrates is a determinant for the success of tissue engineering (TE) strategies. Substrate's topography is reported to play a key role in influencing endothelial cell behavior, namely, on its proliferation, metabolic activity, morphology, migration, and secretion of cytokines and chemokines. Therefore, surface topography of the biomaterial-based grafts is a crucial property that is considered in the development of a new TE approach. Herein, we hypothesize that the surface of Rubus fruticosus leaf plays a crucial role in driving angiogenesis since its architecture resembles the vascular structures at a biologically relevant size scale. For this, we produced biomimetic polycaprolactone (PCL) membranes (BpMs) replicating the surface topography of a R. fruticosus leaf by replica molding and nanoimprint lithography. Our results showed an enhanced performance in terms of proliferation of the human endothelial cell line on top of the BpM. Moreover, an asymmetric cellular spatial distribution among the surface of the BpM was observed. These cells seem to have higher density for longer time periods in the region that replicates the leaf veins. Finally, we assess the angiogenic capacity through a chick chorioallantoic membrane assay, revealing that BpMs are more prone to support angiogenesis than flat PCL membranes. We strongly believe that this strategy can bring new insights into developing TE strategies with an enhanced performance in terms of the vascular integration between the host and the scaffolds implanted.