Prevented Cell Clusters' Migration Via Microdot Biomaterials for Inhibiting Scar Adhesion

Cluster-like collective cell migration of fibroblasts is one of the main factors of adhesion in injured tissues. In this research, a microdot biomaterial system is constructed using alpha-helical polypeptide nanoparticles and anti-inflammatory micelles, which are prepared by ring-opening polymerization of alpha-amino acids-N-carboxylic anhydrides (NCAs) and lactide, respectively. The microdot biomaterial system slowly releases functionalized polypeptides targeting mitochondria and promoting the influx of extracellular calcium ions under the inflammatory environment, thus inhibiting the expression of N-cadherin mediating cell-cell interaction, and promoting apoptosis of cluster fibroblasts, synergistically inhibiting the migration of fibroblast clusters at the site of tendon injury. Meanwhile, the anti-inflammatory micelles are celecoxib (Cex) solubilized by PEG/polyester, which can improve the inflammatory microenvironment at the injury site for a long time. In vitro, the microdot biomaterial system can effectively inhibit the migration of the cluster fibroblasts by inhibiting the expression of N-cadherin between cell-cell and promoting apoptosis. In vivo, the microdot biomaterial system can promote apoptosis while achieving long-acting anti-inflammation effects, and reduce the expression of vimentin and alpha-smooth muscle actin (alpha-SMA) in fibroblasts. Thus, this microdot biomaterial system provides new ideas for the prevention and treatment of tendon adhesion by inhibiting the cluster migration of fibroblasts. A microdot biomaterial system is constructed using alpha-helical polypeptide nanoparticles and anti-inflammatory micelles for inhibiting adhesion of injured tendon. By slowly releasing mitochondria-targeted functional polypeptides and anti-inflammatory agents in an inflammatory environment to promote the inflow of extracellular Ca2+, they can inhibit the N-cadherin expression and promote fibroblast apoptosis, synergistically inhibiting adhesion of injured tendons. image