Table 2.

Different EVs application forms used in animals with experimental periodontal defect

Application Forms	Cell type	Animal model	System composition	Key features	References
Hydrogel delivery system	DPSCs	Mouse	CS hydrogel and DPSC-exosome solution	The loading efficiency of exosomes in DPSC-exosome/CS was about 80%, and the system alleviated periodontitis in mice	Shen et al. [58]
	BMSC	Rat	5% gelatin, 10% Laponite and BMSC-sEV	The nanocomposite hydrogel has a sustained release effect on BMSC-sEV without adverse reactions	Liu et al. [59]
	DFSCs	Rat	2.5% laponite, 1.25% gelatin, and 500 μg/ml sEV	The hydrogel system can be released continuously for 21 days without affecting biological activity	Shi et al. [47]
Collagen sponge scaffold loading system	DFSCs	Rat	SC collagen sponge and DFSC-MVs	CS showed a typical spongy structure and regular pore distribution and facilitated adhesion of MVs	Yi et al. [66]
	MSCs	Rat	Bovine I/III collagen sponge and 40 g exosomes	Exosomes combined with collagen sponge promoted periodontal regeneration without any adverse reactions	Chew et al. [70]
	DFSCs	Rat	Collagen sponge and DFSC-sEV	The collagen sponge group formed scattered new bone fragments and are denser than the control group	Ma et al. [71]
Injectable HA/sEV system	DFSCs	Beagle dog	HA system (Gengigel® containing 5% HA) and 200 μg sEV	HA released sEVs significantly promoted the proliferation and migration of PDLSCs, which was the same as that of sEVs alone	Huang et al. [46]
Dual delivery PLGA microparticles	GMSCs	Rat	PLGA microparticles, minocycline and GMSC-EVs	PLGA microparticles system exerts dual effects of antibacterial and periodontal regeneration	Zarubova et al. [53]