Multifunctional Biomaterial Strategies to Regulate Inflammation and Promote Kidney Repair.

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Nephrology

Background:

• Chronic kidney disease (CKD) is characterized by inflammation, fibrosis, and poor regeneration.
• Current treatments for CKD have limitations in addressing these pathological hallmarks.

Purpose of the Study:

• To develop and evaluate a biofunctional hybrid scaffold (PMEAR/MM/uEV) for kidney regeneration.
• To assess the scaffold's antioxidant, anti-inflammatory, and pro-regenerative properties.

Main Methods:

• Fabrication of a hybrid scaffold integrating poly(lactic-co-glycolic acid)-porcine extracellular matrix, magnesium hydroxide, specific cells, and extracellular vesicles.
• Incorporation of resveratrol and adapalene for enhanced therapeutic effects.
• In vitro assays for epithelial wound closure and cytokine profiling.
• In vivo studies using a 5/6 nephrectomy mouse model to evaluate renal function and histology.
• mRNA sequencing for comprehensive pathway analysis.

Main Results:

• The PMEAR/MM/uEV scaffold demonstrated uniform porosity, pH-buffering, and reactive oxygen species scavenging.
• In vitro studies showed accelerated wound closure, reduced oxidative stress, and an anti-inflammatory cytokine shift.
• In vivo, the scaffold improved kidney function markers (blood urea nitrogen, creatinine), reduced collagen deposition, and upregulated key podocyte and developmental markers.
• Transcriptomic analysis revealed activation of angiogenesis, ECM remodeling, oxidative defense, and immune modulation pathways.

Conclusions:

• The PMEAR/MM/uEV scaffold is an effective multimodal platform for kidney regeneration.
• This approach holds promise for treating chronic kidney disease by addressing inflammation, fibrosis, and impaired regeneration.