Work

Non-viral CRISPR activation system targeting VEGF-A and TGF-β1 for enhanced osteogenesis of pre-osteoblasts implanted with dual-crosslinked hydrogel

Year: 2022

Type: article

Abstract: Healing of large calvarial bone defects remains challenge but may be improved by stimulating bone regeneration of implanted cells. The aim of this study is to specially co-activate transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF-A) genes expressions in pre-osteoblast MC3T3-E1 cells through the non-viral CRISPR activation (CRISPRa) system to promote osteogenesis. A cationic copolymer carrying nucleus localizing peptides and proton sponge groups dimethyl-histidine was synthesized to deliver CRISPRa system into MC3T3-E1 cells with high cellular uptake, lysosomal escape, and nuclear translocation, which activated VEGF-A and TGF-β1 genes expressions and thereby additively or synergistically induced several osteogenic genes expressions. A tunable dual-crosslinked hydrogel was developed to implant the above engineered cells into mice calvaria bone defect site to promote bone healing in vivo. The combination of multi-genes activation through non-viral CRISPRa system and tunable dual-crosslinked hydrogel provides a versatile strategy for promoting bone healing with synergistic effect.

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2022.100356

Authors: Guo Chen, Shaohui Deng, Mingxiang Zuo, Jin Wang, Du Cheng, Bin Chen

Institutions: Sun Yat-sen University, Nanfang Hospital, Southern Medical University, Third Affiliated Hospital of Sun Yat-sen University

Language: English

Topic: Bone Tissue Engineering Materials

Subfield: Biomedical Engineering

Field: Engineering

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,000