Agradecimentos: This research was supported by funding from the National Institutes of Health / National Institute of Dental and Craniofacial Research (R01DE026578 to MCB). IJSA also thanks the CAPES Foundation for financial support (AUX/CAPES/PROEX:0878/2018) and scholarship through the PRINT program (#88887.368381/2019-00). MC acknowledge the financial support from the Reprint project (OCENW.XS5.161) by the Netherlands Organization for Scienti?c Research. RMPR also thanks Dr. Dominik A. Lysek (Credentis) for generously donating the self-assembling peptide P11-4 used in this research. The authors also thank Dr. Nileshkumar Dubey and Dr. Ester Bordini for their help with the cell culture and mineralization experiments. The authors declare no conflict of interest related to this research Ver menos

Abstract: Electrospun scaffolds are a versatile biomaterial platform to mimic fibrillar structure of native tissues extracellular matrix, and facilitate the incorporation of biomolecules for regenerative therapies. Self-assembling peptide P11-4 has emerged as a promising strategy to induce mineralization; however, P11-4 application has been mostly addressed for early caries lesions repair on dental enamel. Here, to investigate P11-4's efficacy on bone regeneration, polymeric electrospun scaffolds were developed, and then distinct concentrations of P11-4 were physically adsorbed on the scaffolds. P11-4-laden and pristine (P11-4-free) electrospun scaffolds were immersed in simulated body fluid and mineral precipitation identified by SEM. Functional groups and crystalline phases were analyzed by FTIR and XRD, respectively. Cytocompatibility, mineralization, and gene expression assays were conducted using stem cells from human exfoliated deciduous teeth. To investigate P11-4-laden scaffolds potential to induce in vivo mineralization, an established rat calvaria critical-size defect model was used. We successfully synthesized nanofibrous (~ 500 nm fiber diameter) scaffolds and observed that functionalization with P11-4 did not affect the fibers' diameter. SEM images indicated mineral precipitation, while FTIR and XRD confirmed apatite-like formation and crystallization for P11-4-laden scaffolds. In addition, P11-4-laden scaffolds were cytocompatible, highly stimulated cell-mediated mineral deposition, and upregulated the expression of mineralization-related genes compared to pristine scaffolds. P11-4-laden scaffolds led to enhanced in vivo bone regeneration after 8 weeks compared to pristine PCL SIGNIFICANCE: Electrospun scaffolds functionalized with P11-4 are a promising strategy for inducing mineralized tissues regeneration in the craniomaxillofacial complex Ver menos