Mineralized nanofibrous scaffold promotes phenamil‐induced osteoblastic differentiation while mitigating adipogenic differentiation

Abstract

Large bone defects represent a significant unmet medical challenge. Cost effectiveness and better stability make small molecule organic compounds a more promising alternative compared with biomacromolecules, for example, growth factors/hormones, in regenerative medicine. However, one common challenge for the application of these small compounds is their side‐effect issue. Phenamil is emerging as an intriguing small molecule to promote bone repair by strongly activating bone morphogenetic protein signaling pathway. In addition to osteogenesis, phenamil also induces significant adipogenesis based on some in vitro studies, which is a concern that impedes it from potential clinical applications. Besides the soluble chemical signals, cellular differentiation is heavily dependent on the microenvironments provided by the 3D scaffolds. Therefore, we developed a 3D nanofibrous biomimetic scaffold‐based strategy to harness the phenamil‐induced stem cell lineage differentiation. Based on the gene expression, alkaline phosphatase activity, and mineralization data, we indicated that bone‐matrix mimicking mineralized‐gelatin nanofibrous scaffold effectively improved phenamil‐induced osteoblastic differentiation, while mitigating the adipogenic differentiation in vitro. In addition to normal culture conditions, we also indicated that mineralized matrix can significantly improve phenamil‐induced osteoblastic differentiation in simulated inflammatory condition. In viewing of the crucial role of mineralized matrix, we developed an innovative and facile mineral deposition‐based strategy to sustain release of phenamil from 3D scaffolds for efficient local bone regeneration. Overall, our study demonstrated that biomaterials played a crucial role in modulating small molecule drug phenamil‐induced osteoblastic differentiation by providing a bone‐matrix mimicking mineralized gelatin nanofibrous scaffolds.

Biomineralized tetramethylpyrazine-loaded PCL/Gelatin nanofibrous membrane promotes vascularization and bone regeneration of rat cranium defects

“…Additionally, although the drug is directly loaded on the surface of nano ber membranes to realize the drug delivery, the controlled release may not meet the demand for tissue regeneration. Biomimetic mineral deposition where drugs are loaded into crystalline HA on scaffolds is an ideal approach for the controlled release of drugs [32]. Herein, TMP was loaded on the PG membrane to use the mineralization of the HA approach.…”

“…Mineralization of PCL/Gelatin nano-membranes was performed as previously reported [32]. Brie y, the PCL/Gelatin membranes were immersed in the nucleation solution (…”

Biomimetic Nanofibrous 3D Materials for Craniofacial Bone Tissue Engineering

“…An in vivo mouse ectopic bone model also demonstrated significantly new bone formed after 4 weeks of implantation. Additionally, our group has developed biomimicking-based drug delivery technique, using HA as a functionalizing agent to improve the mechanical modulus and act as a drug delivery agent for phenamil, as we have previously discussed. , One of the concerns of phenamil is the ability to increase adipogenic activity in addition to the osteogenic activity of stem cells, which limits clinical applicability of the small molecule. , HA can act as an encapsulator for phenamil to provide sustained and localized release of drug, where the addition of HA to GF scaffolds showed a marked decrease in adipogenic staining and markers PPARγ, Fabp4, and LPL. Similar to TISA, HA could evenly coat GF scaffolds while increasing mechanical properties and leaving the porous morphology still complete (Figure ).…”

“…Morphology of (A) GF, (B) GF-HA low-magnification and (C) GF-HA high-magnification images, as shown by SEM. Reproduced with permission from ref . Copyright 2019 John Wiley & Sons.…”