Table 4.

Delivery mechanisms for miRNA-based therapies in periodontal regeneration.

Delivery system	Carrier material	miRNA/Agent loaded	Key features	Outcome	Ref
NF scaffold	PCL nanofibers	miR-22 mimic, miR-126 mimic	High surface-to-volume ratio; acts like ECM; helps cells stick together	Improves iPSCs’ ability to survive and differentiate into bone cells; increases RUNX2, BGLAP, ALPL, SPARK	(115, 116)
Dual-miRNA scaffold	Collagen-nanohydroxyapatite	miR-210 mimic + miR-16 inhibitor	Dual-delivery method; connects bone growth and blood vessel growth	Increase Calcium deposition (10–14 days); 2× bone volume; 2.3× blood vessels	(117)
Nanospheres	Magnesium silicate (MSNs)	miR-146a-5p	Dual effects on bone growth and the immune system control	Encourages hDPSC osteogenesis and M2 polarization while stopping the formation of osteoclasts	(122)
LNPs	LNPs	miR-27 mimic	Targets SFRP1; activates Wnt signaling	increases ALP, RUNX2, COL1, CD31, CD34, VEGF; 6× new blood vessels; 43.9% reduction in bone loss distance	(123)
Hydrogel platform	Photocuring hydrogel	MSN+miR-146a complex	Stimulus-responsive; sustained local release	Confirmed efficacy in the infected mouse mandibular bone defect model	(122)
EXO-based hydrogel	EXOs from hucMSCs + hydrogel (exo@H)	let-7f-5p, miR-203-3p	Lyophilized EXOs were mixed into a hydrogel	Less loss of dental bone, periodontal inflammation, and osteoclast count	(124)
mRNA-LNP	LNPs	mRNA encoding FGF-2	Continuous protein production; superior to recombinant protein	Increase Cell proliferation (72h); faster wound closure (88.4% vs 76.1%); 4.5× POSTN expression	(125)