Table 1.

Natural compound scaffolds/hydrogels used in chondrogenic differentiation under mechanical compression.

Scaffold Base	Additional Compounds	Cell Type	Compression Parameters	Compression Duration	Results after Compression	Reference
Collagen	Collagen I	Human MSCs	10% peak compressive sinusoidal strain at 1 Hz frequency	2 h/day, 1, 4, 7, 14 and 21 days	Upregulated cartilage specific genes: AGG, COL2A1 and SOX9, and prevented expression of COL10A1, and COL1A2.	[80]
	Collagen I	Human MSCs	1% amplitude sinusoidal strain at the three frequencies of 0.01, 0.1, 1 Hz for 10 cycles at each frequency	-	Resistance to compression, increased dynamic properties of the scaffold, more marked viscoelastic behavior over time	[81]
	Alginate	Human MSCs	10% or 15% cyclic compressive strain	4 out of 24 h for up to 21 days	Increased expression of CBFA-1, Sox9, and aggrecan under 15% cyclic compressive strain alone	[82]
Chondroitin sulfate	PEG	Human MSCs	Dynamic loading from 0% to 15% amplitude strain in a sinusoidal waveform at a frequency of 0.3 Hz	0.5 h on, 1.5 off, repeated for 16 h followed by 8 h off, during 1 week	Downregulated Col X, RUNX2 and collagen I/II protein expression	[83]
	PEG	Human MSCs	Dynamic loading 5% strain 0.3 Hz (1.5% s−1); 10% strains 0.3 Hz (3% s−1); 5% strain 1 Hz (5% s−1); 10% strain 1 Hz (10% s−1)).	1 h/day for a week	Upregulated collagen II gene expression	[84]
Hyaluronic acid	Fibrin	Human MSCs	Compressive modulus at 20% strain, 3.39 ± 0.91 kPa to 6.76 ± 0.52 kPa	-	Eased collagen type 1 expression and an increase Sox9 expression	[85]
	Hyaluronan- gelatin composites	Human BMMSCs		4 h/day in the first 7 days of culture	Proteoglycan and collagen contents were significantly higher in the loaded samples compared to unloaded controls	[86]
	Fibrin	Rabbit BMMSCs	Mechanical compression of low-intensity ultrasound (LIUS)	4 weeks of LIUS (1.0 MHz and 200 mW/cm2)	LIUS induces chondrogenic differentiation of MSCs without TGF-ß3 treatment and increased chondrogenic markers	[87]
	Methacrylate	Calve BMMSCs	0.02 N for 5 min to 1000 sec relax and 1% sinusoidal deformation at 1.0 Hz	3, 7, 21, 63 days	Increase in GAG production after 63 days under mechanical load	[88]
Chitosan	Collagen	Rabbit chondrocytes	Cyclic compression of 40% stain, 0.1 Hz	30 min/day for two weeks	Enhanced cells proliferation and GAGs deposition. 82% degree of chitosan deacetylation	[89]
	Oxidized dextran, and teleostean	Human MSCs	0.02 N preload for 500 sec, this consisted of 20% stain, 2 Hz, 0.12 and 0.96 MPa	42 days	Upregulation of aggrecan and collagen II mRNA, and increased GAG and collagen content. 85% degree of chitosan deacetylation	[90]
	Agarose	Human MSCs	Dynamic compression loading was applied at 1 Hz	1 h/day, 14 days.	Total GAG content and GAG/DNA content was significantly higher, as compared to unloaded control.	[91]
	Silk fibrin and nano- hydroxyapatite	Rat BMMSCs	10% compressive strain, 0.5 Hz	2 h action + 4 h pause/cycle, 4 cycles/day	Upregulation of chondrogenesis markers (Aggrecan, Sox-9, and collagen II. 92( ± 2.1)% degree of chitosan deacetylation	[92]
Alginate	-	Rabbit adipose-derived MSCs	1 Hz, with air pressure 21 kPa and different stain magnitudes (0–20%).	2 h per day, 6 days a week	Expression of Col II, SOX9 and aggrecan w/o TGF-ß	[93]
	-	Human MSCs	0.5 Hz frequency and 6813 ± 2195 Pa	21 d.	SOX9 and aggrecan gene expression of uncompressed group was low and increased 15 fold and 7 fold, respectively, for compressed group	[94]