Delivering Multifunctional Peptide-Conjugated Gene Carrier/miRNA-218 Complexes from Monodisperse Microspheres for Bone Regeneration

Abstract

MicroRNAs (miRNAs) play a pivotal role in regulating gene expression and are considered new molecular targets in bone tissue engineering. However, effective delivery of miRNAs to the defect areas and transfection of the miRNAs into osteogenic progenitor cells has been an obstacle in the application. In this work, miRNA-218 (miR-218) was used as an osteogenic miRNA regulator, and a multifunctional peptide-conjugated gene carrier poly­(lactide-co-glycolide)-g-polyethylenimine-b-polyethylene glycol-R9-G4-IKVAVW (PPP-RGI) was developed to condense with miR-218 to form PPP-RGI/miR-218 complexes that were further encapsulated into monodisperse injectable microspheres for enhanced bone regeneration. The PPP-RGI was synthesized via conjugating R9-G4-IKVAVW (RGI), a multifunctional peptide, onto poly­(lactide-co-glycolide)-g-polyethylenimine-b-polyethylene glycol (PPP). A microfluidic and synchronous photo-cross-linking process was further developed to encapsulate the PPP-RGI/miR-218 complexes into monodisperse gelatin methacryloyl microspheres. The monodisperse microspheres controlled the delivery of PPP-RGI/miR-218 to the designated defect site, and PPP-RGI facilitated the transfection of miR-218 into osteogenic progenitor cells. An in vivo calvarial defect model showed that the PPP-RGI/miR-218-loaded microspheres significantly enhanced bone tissue regeneration. This work provides a novel approach to effectively deliver miRNA and transfect targeting cells in vivo for advanced regenerative therapies.

Circ‐ZNF236 mediates stem cells from apical papilla differentiation by regulating LGR4‐induced autophagy

“…MicroRNAs (miRNAs), a small molecular RNA family, are short noncoding RNA sequences that post‐transcriptionally regulate the expression of mRNAs by targeting their 3′‐UTR and participate in various vital processes (Gao et al., 2022; Huang et al., 2019; Jiang et al., 2022; Wang et al., 2021). Previous studies have demonstrated the involvement of miR‐218 in the osteogenic differentiation of MSCs (Karimi et al., 2020; Li, Deng, et al., 2022; Li, Hu, et al., 2021; Shi et al., 2018). Our results confirmed that the odonto/osteogenic differentiation of SCAPs was repressed by a miR‐218‐5p mimics but promoted by a miR‐218‐5p inhibitor.…”

Multifunctional Nanofibrous Hollow Microspheres for Enhanced Periodontal Bone Regeneration

“…Since periodontal bone resorption generally forms irregular alveolar bone defects, injectable biomaterials that can easily fill any shape of defects are more attractive than conventional pre‐formed 3D biomaterials. [ 9 ] Hydrogels are injectable biomaterials and have been tested for bone formation. [ 10 ] However, the limitations of hydrogels include the inferior mechanical property and poor integration with surrounding tissues.…”

Injectable, High Specific Surface Area Cryogel Microscaffolds Integrated with Osteoinductive Bioceramic Fibers for Enhanced Bone Regeneration

“…Minimally invasive surgery-based regenerative therapy is an attractive strategy for bone defect treatment due to its advantages of smaller incisions, faster recovery, and fewer complications in comparison with traditional surgery. , Injectable biomaterials can fill defects with irregular shape and create a local microenvironment that is conducive to tissue regeneration when they are properly prepared and functionalized to accelerate the repair process . Recently, biodegradable microspheres have emerged as one of the most promising injectable microscaffolds with the following features: (1) diverse physical morphology and chemical composition, (2) higher specific surface area than bulk scaffolds, and (3) flexibility in assembly. − Microspheres have formed a platform technique to improve the regeneration of injured bone tissue via providing diverse biochemical and biophysical cues for cell fate modulation. − …”