Post-transplant recurrence of focal segmental glomerular sclerosis: consensus statements.

Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review.

Acute kidney injury in pediatric hematopoietic cell transplantation: critical appraisal and consensus.

Hematopoietic cell transplantation (HCT) is a common therapy for the treatment of neoplastic and metabolic disorders, hematological diseases, and fatal immunological deficiencies. HCT can be subcategorized as autologous or allogeneic, with each modality being associated with their own benefits, risks, and post-transplant complications. One of the most common complications includes acute kidney injury (AKI). However, diagnosing HCT patients with AKI early on remains quite difficult. Therefore, this evidence-based guideline, compiled by the Pediatric Continuous Renal Replacement Therapy (PCRRT) working group, presents the various factors that contribute to AKI and recommendations regarding optimization of therapy with minimal complications in HCT patients.

Bicyclic RGD peptides enhance nerve growth in synthetic PEG-based Anisogels.

Nerve regeneration scaffolds often consist of soft hydrogels modified with extracellular matrix (ECM) proteins or fragments, as well as linear and cyclic peptides. One of the commonly used integrin-mediated cell adhesive peptide sequences is Arg-Gly-Asp (RGD). Despite its straightforward coupling mechanisms to artificial extracellular matrix (aECM) constructs, linear RGD peptides suffer from low stability towards degradation and lack integrin selectivity. Cyclization of RGD improves the affinity towards integrin subtypes but lacks selectivity. In this study, a new class of short bicyclic peptides with RGD in a cyclic loop and 'random screened' tri-amino acid peptide sequences in the second loop is investigated as a biochemical cue for cell growth inside three-dimensional (3D) synthetic poly(ethylene glycol) (PEG)-based Anisogels. These peptides impart high integrin affinity and selectivity towards either αvß3 or α5ß1 integrin subunits. Enzymatic conjugation of such bicyclic peptides to the PEG backbone enables the formulation of an aECM hydrogel that supports nerve growth. Furthermore, different proteolytic cleavable moieties are incorporated and compared to promote cell migration and proliferation, resulting in enhanced cell growth with different degradable peptide crosslinkers. Mouse fibroblasts and primary nerve cells from embryonic chick dorsal root ganglions (DRGs) show superior growth in bicyclic RGD peptide conjugated gels selective towards αvß3 or α5ß1, compared to monocyclic or linear RGD peptides, with a slight preference to αvß3 selective bicyclic peptides in the case of nerve growth. Synthetic Anisogels, modified with bicyclic RGD peptides and containing short aligned, magneto-responsive fibers, show oriented DRG outgrowth parallel to the fibers. This report shows the potential of PEG hydrogels coupled with bicyclic RGD peptides as an aECM model and paves the way for a new class of integrin selective biomolecules for cell growth and nerve regeneration.

Synthetic 3D PEG-Anisogel Tailored with Fibronectin Fragments Induce Aligned Nerve Extension.

An enzymatically cross-linked polyethylene glycol (PEG)-based hydrogel was engineered to promote and align nerve cells in a three-dimensional manner. To render the injectable, otherwise bioinert, PEG-based material supportive for cell growth, its mechanical and biochemical properties were optimized. A recombinant fibronectin fragment (FNIII9*-10/12-14) was coupled to the PEG backbone during gelation to provide cell adhesive and growth factor binding domains in close vicinity. Compared to full-length fibronectin, FNIII9*-10/12-14 supports nerve growth at similar concentrations. In a 3D environment, only the ultrasoft 1 w/v% PEG hydrogels with a storage modulus of ∼10 Pa promoted neuronal growth. This gel was used to establish the first fully synthetic, injectable Anisogel by the addition of magnetically aligned microelements, such as rod-shaped microgels or short fibers. The Anisogel led to linear neurite extension and represents a large step in the direction of clinical translation with the opportunity to treat acute spinal cord injuries.

Metal-Organic Gels Based on a Bisamide Tetracarboxyl Ligand for Carbon Dioxide, Sulfur Dioxide, and Selective Dye Uptake.

A metal-organic gel (metallogel) based on the new tetracarboxyl ligand N1, N4-(diterephthalic acid)terephthalamide in combination with chromium(III) has been converted into its xero- and aerogel and demonstrated to have excellent specific sorption properties for dyes in its metallogel state, where fuchsine is adsorbed faster than the two other dyes, calcein and disulfine blue, and for water, sulfur dioxide and carbon dioxide in its xero- and aerogel state. The metallogel showed very good shape retention and could be extruded from molds in designed shapes. In a rheology experiment, the storage modulus was determined to be 1440 Pa, and the metallogel is elastic up to 3 Hz, breaking at strains higher than 0.3%. Additional metallogels utilizing the same ligand with a wide range of metal ions (Al(III), Fe(III), Co(III), In(III), and Hg(II)) have also been synthesized, and the aluminum and mixed aluminum-chromium derivative were also converted into its aerogel. The highly porous Cr, Al, and AlCr metal-organic aerogels proved stable against water vapor in a physisorption experiment and were used to model breakthrough curves for SO2/CO2 gas mixtures with the idealized adsorbed solution theory from their physisorption isotherms. The breakthrough simulation utilized SO2/CO2 equivalencies from a real world application and showed effective retention of SO2 from the gas mixture. Furthermore, the materials in this work exhibit the highest SO2 uptake values for metal-organic aerogels so far (up to 116.8 cm3 g-1, or 23.4 wt %).

Biofunctionalized aligned microgels provide 3D cell guidance to mimic complex tissue matrices.

Natural healing is based on highly orchestrated processes, in which the extracellular matrix plays a key role. To resemble the native cell environment, we introduce an artificial extracellular matrix (aECM) with the capability to template hierarchical and anisotropic structures in situ, allowing a minimally-invasive application via injection. Synthetic, magnetically responsive, rod-shaped microgels are locally aligned and fixed by a biocompatible surrounding hydrogel, creating a hybrid anisotropic hydrogel (Anisogel), of which the physical, mechanical, and chemical properties can be tailored. The microgels are rendered cell-adhesive with GRGDS and incorporated either inside a cell-adhesive fibrin or bioinert poly(ethylene glycol) hydrogel to strongly interact with fibroblasts. GRGDS-modified microgels inside a fibrin-based Anisogel enhance fibroblast alignment and lead to a reduction in fibronectin production, indicating successful replacement of structural proteins. In addition, YAP-translocation to the nucleus increases with the concentration of microgels, indicating cellular sensing of the overall anisotropic mechanical properties of the Anisogel. For bioinert surrounding PEG hydrogels, GRGDS-microgels are required to support cell proliferation and fibronectin production. In contrast to fibroblasts, primary nerve growth is not significantly affected by the biomodification of the microgels. In conclusion, this approach opens new opportunities towards advanced and complex aECMs for tissue regeneration.

Physical Polyurethane Hydrogels via Charge Shielding through Acids or Salts.

Physical hydrogels with tunable stress-relaxation and excellent stress recovery are formed from anionic polyurethanes via addition of acids, monovalent salts, or divalent salts. Gel properties can be widely adjusted through pH, salt valence, salt concentration, and monomer composition. We propose and investigate a novel gelation mechanism based on a colloidal system interacting through charge repulsion and chrage shielding, allowing a broad use of the material, from acidic (pH 4-5.5) to pH-neutral hydrogels with Young's moduli ranging from 10 to 140 kPa.