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Table 2 Mechanical stimulation on cell containing hydrogel and responses

From: Progress in biomechanical stimuli on the cell-encapsulated hydrogels for cartilage tissue regeneration

Cell type /Hydrogel

Preculture time

Mechanical stimuli

Duration

Response

Ref

Rabbit BM-MSCs / Agarose

24 h

Compression/10% strain /1 Hz

4 h/day, 14 days

-Aggrecan and collagen type II expression increased in all groups (TGF-β, TGF-β + loading, Loading)—TGF-β1 gene expression in both loading and TGF-β treatment. -No change in DNA content after stimulation.—No collagen type X expression

[131]

Human chondrocytes/ collagen type I

-

Compression/10% strain /0.3 Hz

Continuous, 28 days

-Upregulation of Col II and Col I and MMP-13, down regulation of aggrecan—No change in the ratio of Col II/ Col I mRNA expression. 

-Enhanced stiffness of construct in loaded sample

[103]

Human synovium-derived mesenchymal stem cells (SMSCs)/ Agarose

1 day and 21 days

10 kPa/ 0.25 Hz

1 h/day till day 28

-Loading after 21 days preculture increased aggrecan and COL2α1 expression level and suppressed hypertrophy markers including COL1α1, COL10α1, MMP13, RUNX2, and ALP

[98]

Chondrocyte/ Fibrin-polyurethane

5 days

10–20% strain with 0.5 Hz and simultaneous shear motion by ball oscillation at ± 25° and 0.5 Hz

1 h loading, twice per day (8 h free swelling between loading cycles) over 5 consecutive days

-Upregulation of COMP and PRG4 gene -Increased Col2/Col1 & ACAN/VCAN, MMP3 and MMP13 remained relatively stable. -No effect on GAG production per cell

[132]

iPS-MP/ photo crosslinkable hydrogel (8-arm PEG-norbornene, ChS-SH, CRGDS (Genscript), PEG dithiol, and Irgacure 2959)

7 days

Intermittent unconfined dynamic compressive strains applied at 5% peak to peak strain (2.5% amplitude strain) at 1 Hz with 23 h of rest under a tare strain of < 0.1%

1 h/day for 3 weeks

-Synergistic effect of dynamic loading and TGF-B3 was the best condition to induce stable chondrogenesis and inhibit hypertrophy

[123]

Human bone marrow stromal cells (hMSCs) /Fibrin hydrogel

0, 2, 4, or 6 weeks

1 Hz to an amplitude of 10% strain, after a 0.01 N preload

2 h/day, 5 days per week/2 weeks

-Enhanced COL2A1 and ACAN mRNA expression in more than 2 weeks priming samples -Increased COL2A1 and COL10A1 and suppressed SOX9 expression with no change on ACAN after immediate mechanical loading (No chondrogenic priming) -Enhanced GAG and collagen deposition and mechanical properties by increasing priming time

[20]

Primed MSCs/MeHA hydrogel (In vivo)

1 day

10% peak compressive sinusoidal strain at 1 Hz superimposed on a 5% compressive tare strain

4 h/day and 5 days per week/14 days

-Dynamic loaded constructs showed cartilage defect healing in Rat and nude mice

[79]

Human articular chondrocytes (in vivo)/Fibrin

-

Perfusion, 2.5 µL/s

21 days

-Accumulated and more distributed GAGs in the perfused samples -Accumulation of collagen type II in perfused gels

[133]

Human articular chondrocytes /Agarose

-

Hydrostatic pressure and/or deviatoric stress

4 days loading and 3 days static culture (7 days in total)

-Cell proliferation with mechanical loading -Increase in aggrecan and collagen type II at day 7 in HP sample -Increase in aggrecan and collagen type II at day 4 in deviatoric stress and combined HP/ deviatoric stress sample

[129]

Primary bovine articular chondrocytes Fibrin-hyaluronan based hydrogel

5 days

10%/0.5 Hz compression, 25°/0.5 Hz rotation

1 h/day, 14 days

-sGAG/DNA upregulation in loaded samples both in the presence or absence of FGF-18v

[122]

Porcine bone marrow (BM) and infrapatellar fat pad (FP) derived stem cells/Agarose

21 days

Compression 10% strain,1 Hz

1 h/day, 21 days

-Increase in sGAG and collagen content after loading in both cells -An increase in DNA content was in FP samples after loading-Relatively constant DNA content in BM samples after loading

[114]

Porcine bone marrow derived multipotent stromal cells (BMSCs) and infrapatellar FP-derived multipotent stromal cells (FPSCs)/ Agarose

24 h

HP/10 MPa /1 Hz

4h/day, 5days/week for5 weeks

-Increase sGAG in both groups -Enhanced collagen accumulation in BMSCs -HP reduced hypertrophic differentiation and endochondral ossification in BMSC -HP caused a stable cartiligous phenotype in FPSC group

[115]

MC-PU/MSC

2 days

Compression and shear strain (Shear ± 25° at 1 Hz/Compression 10–20%, 1 Hz)

1 h/day for 21 consecutive days

High collagen II expression and low COL-X expression in loaded sample

[127]