Table 4.

Application of hydrogel-based delivery strategies in alleviating inflammatory response in IVDD.

Year	Product	Anti-inflammatory therapeutic agents	Administration methods	Outcome	Reference
2022	Celecoxib-loaded chitosan hydrogel	Celecoxib	In situ injection	Thermosensitive injectable; anti-inflammatory and pain-relieving	[252]
2012	Chitosan/PGA nanocarriers with Df loaded within HA hydrogel	Diclofenac (Df)	In situ injection	In situ anti-inflammatory drug delivery system; controlled release by pH changes	[246]
2021	ASP-Lip@GelMA	Aspirin	In situ injection	Cover the inflammatory cycle after intervertebral disc surgery to inhibit inflammatory factor expression and attenuate the release of HMGB1.	[247]
2022	Hydrogel loaded with curcumin and miRNA	Anti-inflammatory curcumin and a cholesterol-modified miRNA-21 inhibitor	In situ injection	Inflammation-responsive sustained release of Antagomir-21 promoted ECM regeneration of NPCs by promoting autophagy activation. Promote the polarization of macrophages to M2 phenotypes.	[249]
2018	FibGen with CHS and infliximab	Infliximab, an anti-TNF-α drug	In situ injection	Reduce the levels of pro-inflammatory cytokines. Control the release rate of infliximab in FibGen by adjusting the drug loaded.	[98]
2021	dECM@exo	ADSCs exosomes	In situ injection	Inhibits the pyroptosis of NPCs.	[251]
				Regulates inflammatory complexes and metalloproteinases.
2022	AEs/SF cryogel	AF cell-derived exosomes	In situ injection	Anti-inflammatory and antioxidant stress.	[253]
				Cell recruitment and regulating fibrocartilage differentiation abilities. Promoting the polarization of macrophages from the M1 to M2 phenotype
2018	PCLA–PEG–PCLA hydrogel with celecoxib	Celecoxib	In situ injection	Thermoresponsive.	[71,73]
				Reduction of back pain.
				Anti-inflammation
2015	CXB-loaded pNIPAAM MgFe-LDH hydrogel	Celecoxib	In situ injection	Controlled release of CXB resulting in suppressed PGE2 levels for 28 days; Anti-inflammation	[254]
2019	Rapa@Gel	ROS-scavenging scaffold with rapamycin	In situ injection	Scaffold reduces inflammatory responses.	[255]
				Increase in the percentage of M2-like macrophages
2013	FA–G/C/GP hydrogel	FA, a member of the polyphenol family	In situ injection	Inhibit IκB kinase activity and down-regulate pro-inflammatory gene Reduce inflammation caused by oxidative stress.	[258]
				Inhibit the apoptosis of H2O2-induced oxidative stress NP cells.
				Down-regulation of MMP-3, up-regulation of aggrecan and collagen-II.
2023	OPF/SMA hydrogel with PLGA microspheres containing IL-4 and kartogenin	IL-4, kartogenin	In situ injection	Induced macrophages to transition from the M1 to M2 phenotype.	[257]
				Promoted cell proliferation and improved cell viability.
				Reduced levels of MMP13 expression
2021	TGF-β3-loaded graphene oxide peptide hybrid hydrogels	TGF-β3, graphene oxide - self-assembling peptide	In situ injection	Upregulation of NP-specific genes.	[264]
				Direct NP cell fate and function.
				Early reversal of IVDD.
2022	Cur@PLA NPs in lginate/gelatin hydrogel	Curcumin	In situ injection	Curcumin-mediated autophagy to relieve IVDD.	[265]
				Reduces pro-inflammatory cytokines IL-1, IL-6, and IL-8.
2023	HA/CS hydrogels	Phenylboronic acid-modified CS (CS-PBA)	In situ injection	pH-responsive	[263]
				Inhibit inflammatory cytokine expression and maintain anabolic/catabolic balance.
2022	RTNPs/F127 hydrogels	Immunomodulatory and TNF-α inhibitor-thalidomide selective JAK1/2 inhibitor-ruxolitinib	In situ injection	Protective effects on NP cell apoptosis.	[239]
				Inhibition of inflammation responses of NPCs and degradation of ECM
2023	GelMA/HAMA hydrogel with mesoporous silica nanoparticles and TGF-β3	Mesoporous silica nanoparticles, TGF-β3	In situ injection	Eliminate ROS and induce anti-inflammatory M2 type.	[261]
				Macrophage polarization.
				TGF-β3 recruits AF cells and promotes ECM secretion.
2022	siSTING@HPgel	siSTING to intervene in the abnormal STING signal	In situ injection	PAMAM formed complexes with siRNA to promote siRNA transfection.	[259]
				Injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP cells.
				Significantly eased IVDD inflammation and slowed IVDD
2023	GelMA/HAMA/MSNs modified by ceria and TGF-β3	Ceria TGF-β3	In situ injection	Eliminate ROS and induce anti-inflammatory M2-type macrophages.	[261]
				Recruit AF cells and promote ECM secretion.
2019	Fibrin hydrogels with EW2871	EW2871, a macrophage recruitment agent	In situ injection	Promotes recruitment of anti-inflammatory macrophages.	[262]
2023	Hydrogel laden with PRP and SIM nano micelles	Simvastatin and platelet-rich plasma	In situ injection	Excellent biocompatibility and slow biodegradability, anti-inflammatory effects and high mechanical characteristics	[266]
2020	WJ-MSCs-loaded HAMC	Wharton's Jelly-derived MSCs	In situ injection	Overall decrease in inflammation of the disc.	[267]
				Attenuation of the activation of iNOS, MMP-13, ADAMTS4, and COX-2, and significant up-regulation of ECM
2014	Hydrogel with MSCs	Porcine MSCs	In situ injection	Persistence of metabolically active pMSC after 3 d in vivo	[268]
2021	HyPRP/HA/BTX hydrogel loaded with MSCs	HyPRP	In situ injection	PRP induces resident cells to synthesize additional biological factors.	[267]
				Exerts an anti-inflammatory effect via the NF-κB pathway.
2018	Genipin-crosslinked hydrogel with ADSCs	Genipin, MSCs	In situ injection	ADSCs differentiate into an NP-like phenotype and increase ECM.	[269]
				Partly regenerate the degenerated NP.
				Genipin exerts anti-inflammatory effects.