A Porous Hydrogel Scaffold Mimicking The Extracellular Matrix With Swim Bladder-derived Collagen For Renal Tissue Regeneration

BackgroundThe chronic kidney disease(CKD)is growingly identified as a public health issue due to the high incidence and prevalence globally,affecting approximate 8～16%of people worldwide.Despite the constantly rising incidence,the available treatment for CKD is still limited.Dialysis has the capability to partially substitute renal filtration function through clearing certain metabolic wastes from the blood,but dialysis frequently gives rise to an inferior life’s quality for patients and is poorly tolerated.When CKD develops into end-stage renal disease(ESRD),kidney transplantation is the only effective therapeutic approach,but the shortage of donated organs and the adverse effects in long-term usage of immunosuppressants restrict its extensive clinical practice.To address these problems,in situ regeneration strategy through offering an inductive template to guide cellular behaviors,recellularization and functional organ recovery in the injured area may be a promising renal placement therapy.ObjectiveBy in situ regeneration strategy,the hydrogel scaffold was implanted into partially nephrectomized rat as a functional induction template to recellularize the resected area and promote repair after renal injury.Methods1.The extracellular matrix-mimicking hydrogel scaffolds were developed through chemical cross-linking between swim bladder-derived natural collagen(COL)and chondroitin sulfate(CS)derivatives,and the prepared hydrogels were characterized by SEM and the detection of the swelling and mechanical properties.2.Detect the biocompatibility of biomimetic hydrogel;F-actin staining,immunofluorescence and western blot were used to study the effects of different hydrogels on the morphology and function of mesangial cells.3.Hydrogel scaffolds were implanted into the resected site of the left renal in 4/6 nephrectomized rats,and the effects of different hydrogel scaffolds on the repair after renal injury were investigated by renal function detection,H&E and Masson staining.Results1.The prepared 1COL/2CS hydrogel has high porosity with average pore size of about 100 μm,uniform pore distribution,good thermal stability and appropriate swelling and mechanical properties.2.1COL/2CS hydrogel showed high biocompatibility,and the expression levels of fibronectin and α-SMA secreted by the cells in the 1COL/2CS hydrogel were lower than those in the pure 2COL hydrogel.3.At 8 weeks after being implanted in partially nephrectomized rat model,the 1COL/2CS scaffold enabled it recruit more native kidney cells,reduce the tubular damage,and even induce the regeneration of renal tubular-like tissue and restore renal metabolic function more effectively comparing with the pure 2COL and 2CS scaffold.ConclusionIn this study,we developed an extracellular matrix-mimicking hydrogel using polysaccharide CS and COL I extracted from grass carp swim bladder.We found that the 1COL/2CS hydrogel exhibited excellent biocompatibility in vitro and helped to guide cell behaviors in vivo,and the developed 1COL/2CS bionic hydrogel could be severed as an in situ tissue engineering platform for renal repair.In summary,this study highlighted a functional scaffold for kidney tissue repair.