Table 3.

Application of microsphere delivery strategies in alleviating the inflammatory response in IVDD.

Year	Product	Anti-inflammatory Therapeutic agents	Administration methods	Outcome	Reference
2019	EGCG-loaded gelatin microparticles	EGCG (epigallocatechin 3-gallate)	Cells and organ models	EGCG microparticles inhibited IL-1β-dependent expression of IL-6, IL-8, COX-2, MMP1, MMP3, and MMP13. Inhibits oxidative stress-induced death of IVDD cells by activating the PI3K/Akt pathway protecting mitochondrial membranes from depolarization	[236]
2022	MS@MCI	MnO2 and lactate oxidase	In situ injection	Eliminated oxidative and inflammatory stress to achieve a long-term oxygen-promoted lactate exhaustion effect, promoted ECM metabolism and cell survival	[232]
2022	psh-circSTC2-lipo@MS	circSTC2-silencing genes	In situ injection	DOTAP improves delivery efficiency and the stability of gene therapy, effectively silencing circSTC2 expression in NP cells to maintain ECM metabolism balance	[234]
2019	NP-lC-seeded GDF-5-loaded GMs	NP-lCs, growth and differentiation factor-5	In situ injection	Disc height recovered, water content elevated, and NP cells and ECM were restored	[235]
2018	CXB-PEAMs	Celecoxib, a selective COX-2 inhibitor	In situ injection	Anti-inflammatory and anti-degenerative effects on NP cells from degenerated IVDDs, a COX-2 inhibitor addresses pain related to IVDD	[72]
2018	Polymeric capsules	Catalase-loaded polymer capsules with tannic acid	In situ injection	Tannic acid has a higher scavenging capacity for hydrogen peroxide, and hydroxyl radicals attenuate the expression of major proteolytic enzymes in an IL-1β induced inflammation model of NP.	[242]
2023	Mg@PLPE MS	PBT-co-EGDM, Mg, H2	In situ injection	ROS-responsive controlled H2 release platform has significant antioxidative and anti-inflammatory effects.	[238]
2012 2014	(PLGA) microspheres loaded with interleukin-1 receptor antagonist	IL-1β receptor antagonist	In vitro model and in situ injection	Effectively attenuates IL-1β-mediated inflammatory changes in an engineered NP construct in vitro. Sustained delivery of anti-inflammatory agents may effectively prevent catabolic changes during early-stage disc degeneration but is unlikely sufficient to regenerate a painful and severely degenerated NP.	[240]
2020	PLLA MS-BNP	Recombinant human soluble TNF receptor type II (rhsTNFRII)	In situ injection	Expression of TNF-α is significantly inhibited, a significant regeneration in NP occurred	[241]
2012	Dex/bFGF PLGA microspheres	Dexamethasone and growth factors	Cells and organ models	Programmed to release dexamethasone and bFGF locally. No cytotoxicity against rMSCs; improved rMSC growth and differentiation into NP-like cells and reduced the inflammation.	[243]