The promotion of bone regeneration through positive regulation of angiogenic–osteogenic coupling using microRNA-26a

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

“…The use of commercial cationic lipids in biomaterial-based approaches to deliver miRNA therapeutics is exemplified by the widespread use of Lipofectamine 2000 [53][54][55][56] along with Lipofectamine RNAiMAX [57] and SiPORT NeoFx. [58] Generally, cationic lipids complex with the miRNA cassettes through electrostatic interaction, and the overall positive charge of the complex dictates the cellular uptake, although neutrally charged liposomes can also encapsulate the cargo within their core. Complexes formed by encapsulation of the miRNA cargo, as opposed to charge adsorption, are not limited to lipid-based vectors and have also shown effective delivery profiles in RM applications.…”

“…[102,106] Whether one of the routes may be better suited for clinical translation remains to be elucidated, although in situ transfecting scaffolds hold greater potential to exist as "off-the-shelf" products. [107] Many distinct scaffold types have been tuned to serve the purpose of miRNA delivery, including several hydrogels, [58,92,106,[108][109][110][111][112][113][114] electrospun fibers, [63,[115][116][117][118] and more prolifically porous or spongy scaffolds. [46,47,50,54,55,96,112,[119][120][121][122][123][124][125][126][127][128][129][130] Before reviewing the details of their applications, summarized in Table 2 and described further in the next section, we will discuss the key characteristics making these materials amenable to miRNA delivery.…”

“…Certain materials are more applicable for a fabrication technique or a type of formulation. For example, PEG is a synthetic polymer frequently employed in the preparation of hydrogels, such as the commercial HyStem-HP utilized by Li et al to deliver miR-26a mimics, [58] or the PEG-norbornene system for human bone marrow derived (BM)-MSCs nucleofected with a dual miR-148b mimic + miR-489 inhibitor combination. [106] An in situ forming PEG-hydrogel has also been the supporting biomaterial of an UV-triggered "on-demand" miR-20a release system.…”

“…[58,63,146] Li et al [58] documented the first report in 2013 using BM-MSCs, HyStem-HP hydrogel, and miR-26a mimic. They demonstrated almost full repair of the defect 12 weeks postimplantation and significantly enhanced vascularization confirming that miR-26a had the capacity to regulate endogenous angiogenic-osteogenic coupling for enhanced bone regeneration.…”

“…Following 12 weeks implantation, histological assessment showed markedly enhanced bone formation. The final and most eloquent report went a few steps further and delivered HP-PEI-miR-26a polyplexes on a nanofibrous PLLA scaffold without an external cell source in contrast to the earlier reports [58,146] and of great importance, mechanistically identified the bone regeneration target gene for miR-26a for the first time. [63] To further support the spatiotemporal release of the miRNA, the miRNA-loaded polyplexes were also encapsulated in biodegradable PLGA microspheres which were then immobilized onto the scaffolds.…”