Table 2.

Common strategies of biomaterial-based immunotherapy for treating periodontitis.

Targeted immune cells	Biomaterial system	Animal model	Key findings	References
Macrophages	Controlled release of PLGA microparticles loaded with CCL2	Murine periodontitis model	CCL2-loaded microparticles decreased the M1:M2 ratio and established an anti-inflammatory microenvironment that prevented alveolar bone loss	(154)
	Liposomes loaded with resveratrol	Murine periodontitis model	Resveratrol-loaded liposomes reduced inflammation in the gingival tissues and ameliorated alveolar bone resorption, accompanied by an increased expression of M2 markers	(155)
Regulatory T-cells	PLGA microparticles loaded with CCL22	Murine periodontitis model/canine periodontitis model	CCL22 loaded microparticles decreased pro-inflammatory cytokines and reduced alveolar bone resorption in both the murine and canine periodontitis models	(156)
	PLLA nanofibrous spongy microspheres and mesoporous silica nanoparticles loaded with IL-2, TGFβ and miR-10a	Murine periodontitis model	Injectable formulation enriched and expanded regulatory T-cells locally and mediated against periodontal bone loss	(157)
	Microspheres were utilized to deliver IL-2, TGFβ, and rapamycin	Murine periodontitis model	Microspheres decreased alveolar bone loss by increasing the local population of regulatory T-cells	(158)
	Injectable hydrogel comprised of polyethylene glycol was utilized to deliver prolyl hydroxylase inhibitor	Murine periodontitis model	Hydrogel loaded with the prolyl hydroxylase inhibitor significantly elevated the local abundance of regulatory T-cells in the periodontal tissue and reduced alveolar bone resorption	(159)
Cytokine IL-17A secreted by IL-17 cells	Anti-IL-17A antibodies were incorporated into PLGA microparticles	Murine periodontitis model	The released antibodies from the PLGA microparticles inhibited alveolar bone loss and suppressed osteoclastic activity	(160)
Macrophages	Gold nanoparticle size (5–45 nm) can influence macrophage polarization	Rat periodontitis model	45 nm gold nanoparticles were effective at promoting M2 macrophages and they showed significant increase of bone formation and attachment	(161)
Uninvestigated	Injectable thermosensitive hydrogel composed of chitosan and β-glycerophosphate	Canine periodontitis model	Hydrogel promoted significant regeneration of periodontal ligament, formation of new bone and cementum without encapsulating any therapeutic agents. However, the hydrogel-host immune response was not studied	(162)