Mineralizing Gelatin Microparticles as Cell Carrier and Drug Delivery System for siRNA for Bone Tissue Engineering

Abstract

The local release of complexed siRNA from biomaterials opens precisely targeted therapeutic options. In this study, complexed siRNA was loaded to gelatin microparticles cross-linked (cGM) with an anhydride-containing oligomer (oPNMA). We aggregated these siRNA-loaded cGM with human mesenchymal stem cells (hMSC) to microtissues and stimulated them with osteogenic supplements. An efficient knockdown of chordin, a BMP-2 antagonist, caused a remarkably increased alkaline phosphatase (ALP) activity in the microtissues. cGM, as a component of microtissues, mineralized in a differentiation medium within 8–9 days, both in the presence and in the absence of cells. In order to investigate the effects of our pre-differentiated and chordin-silenced microtissues on bone homeostasis, we simulated in vivo conditions in an unstimulated co-culture system of hMSC and human peripheral blood mononuclear cells (hPBMC). We found enhanced ALP activity and osteoprotegerin (OPG) secretion in the model system compared to control microtissues. Our results suggest osteoanabolic effects of pre-differentiated and chordin-silenced microtissues.

Advanced strategies of scaffolds design for bone regeneration

“…Many approaches have been explored to prepare gene and interfering RNA-activated scaffolds for bone tissue engineering, including activating scaffolds with plasmid DNA, [76] small interfering RNA, [97][98][99] and micro-RNA. [100][101][102] As a means to overcome the biological barrier, bisphosphonate lipid-like materials with a high affinity for bone minerals could effectively deliver mRNA therapeutics to the bone microenvironment in vivo (Figure 6a).…”

Emerging delivery systems based on aqueous two-phase systems: A review

“…All-aqueous droplets can be readily transformed into microparticles with simple structures using methods such as light triggering and heat triggering. Microparticles have emerged as versatile functional biomaterials with applications ranging from drug delivery and tissue engineering to biosensing and beyond 82 , 83 . Herein, we briefly discuss several preparation strategies for transforming ATPS droplets into microparticles ( Table 3 ) 20 , 84 , 85 , 86 , 87 , 88 , 89 , 90 .…”

New Hope for Treating Intervertebral Disc Degeneration: Microsphere-Based Delivery System

“…In recent years, research on nonviral gene delivery has become popular. From the nanoscale (e.g., liposomes ( Wang et al, 2021 ; Yu et al, 2022 ), complex micelles ( Yoshinaga et al, 2021 ; Yoshinaga et al, 2022 ), and exosomes ( Cui et al, 2022 ; Xu et al, 2022 )) to the micron scale (such as microspheres ( McMillan et al, 2018 ; Hinkelmann et al, 2022 )) or combined forms of nanoparticles and microspheres ( Feng et al, 2017 ; Feng et al, 2020 ; Chang et al, 2022 ), more options for nonviral vectors have been provided. Importantly, genetic factors contribute to the worsening of IVDD, and gene therapy approaches are expected to improve the poor genetic cascade regulation of IVD.…”