Κυριακή 18 Σεπτεμβρίου 2022

Immunomodulatory fibrous hyaluronic acid‐Fmoc‐diphenylalanine‐based hydrogel induces bone regeneration

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Abstract

Aim

To investigate the potential of an ultra-short aromatic peptide hydrogelator integrated with hyaluronic acid (HA) to serve as a scaffold for bone regeneration.

Materials and methods

Fluorenylmethyloxycarbonyl-diphenylalanine (FmocFF)/HA hydrogel was prepared and characterized using microscopy and rheology. Osteogenic differentiation of MC3T3-E1 preosteoblasts was investigated using Alizarin red, alkaline phosphatase and calcium deposition assays. In vivo, 5-mm diameter calvarial critical-sized defects were prepared in 20 Sprague-Dawley rats and filled with either FmocFF/HA hydrogel, deproteinized bovine bone mineral, FmocFF/Alginate (Alg) hydrogel or left unfilled. 8 weeks following implantation, histology and micro-CT analyses were performed. Immunohistochemistry was performed in 6 rats to assess the hydrogel's immunomodulatory effect.

Results

A nanofibrous FmocFF/HA hydrogel with a high storage modulus of 46KPa was prepared. It supported osteogenic differentiation of MC3T3-E1 preosteoblasts and facilitated calcium deposition. In vivo, the hydrogel implantation resulted in approximately 93% bone restoration. It induced bone deposition not only around the margins, but also generated bony islets along the defect. Elongated M2 macrophages lining at the periosteum-hydrogel interface were observed 1 week after implantation. After 3 weeks, these macrophages were dispersed through the regenerating tissue surrounding the newly formed bone.

Conclusion

FmocFF/HA hydrogel can serve as a cell-free, biomimetic, immunomodulatory scaffold for bone regeneration.

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