Table 2.

Bioactive factors in therapeutic target, principle, and characteristic.

Type of bioactive factors	Target of action	Principle	Characteristic	Ref.
AHI	ACSCs; ECM	Promoting ACSCs proliferation and differentiation and ECM production.	Excellent sustained release effect; injection in situ.	[157]
IGF-I	IL-1β; TNF-α	Decreasing expression of detrimental proinflammatory mediators (IL-1β, TNF-α)	Sequential releasing in a spatiotemporal manner.	[73,161]
Nap-FFG-GYGSSSRRAPQT	ADSCs	Activating IGF-1 receptor and up-regulating the expression of cartilage-related genes in ADSCs.	Substitution of self-assembled polypeptide polymers.	[152]
miR-17	MMP3/13; ADAMTS5; NOS2	Decreasing HIF-1α signaling to maintain physiological anabolic and catabolic balance.	Maintaining cartilage homeostasis and preventing OA simultaneously.	[158,162]
HL-43	EP4	Enhancing cartilage anabolism through Sox9 signaling and inhibiting it via STAT3 signaling.	Low toxicity; desirable bioavailability	[163,164]
IL-4	M1/M2 macrophage	Immune regulation on decellularized cartilage ECM scaffolds.	Precise and active immunomodulatory.	[146]
SDF-1 and KGN	CXCR4 receptors; runt-related transcription factor (RUNX)	Stem cell homing; stimulating RUNX1 expression.	Cell-free system; long-time sustained release.	[147]
KGN	PB-MSCs	Activating multiple cartilage-related genes and signaling pathways; promoting chondrogenic differentiation of PB-MSCs.	In situ gelation; sustained release.	[155]
SDF-1α and TGF-β3	MSCs; ECM	Increasing cell migration and matrix formation	Cell-free scaffold; dual-factor release	[153]