Biochemical Stimulus-Based Strategies for Meniscus Tissue Engineering and Regeneration

Table 1

Commonly used growth factors for cartilage and meniscus tissue engineering and regeneration.

Growth factor	Cell types	Culture conditions	Findings	Authors and reference
TGF-β1	Meniscal fibrochondrocytes	Monolayer culture	Increase collagen and GAG synthesis	Tanaka et al. [12]
				Pangborn and Athanasiou [13]
TGF-β	Meniscal fibrochondrocytes	Monolayer/alginate beads/explant culture	Increase proteoglycan synthesis	Collier and Ghosh [14]
TGF-β1	Meniscal fibrochondrocytes	PGA scaffold culture	Increase collagen and GAG synthesis	Pangborn and Athanasiou [15]
TGF-β1	Meniscal fibrochondrocytes	Meniscus explant culture	Increase collagen and GAG synthesis	Imler et al. [16]
TGF-β1 and C-ABC	Cocultures of meniscal fibrochondrocytes and articular chondrocytes	Agarose scaffold culture	Increase collagen synthesis and the Young’s modulus and ultimate tensile strength	MacBarb et al. [17]
TGF-β1 and C-ABC	Meniscal fibrochondrocytes and articular chondrocytes	Agarose scaffold culture	Enhance compressive and tensile properties	Huey and Athanasiou [18]
TGF-β1 and HP	Meniscal fibrochondrocytes	PLLA scaffold culture	Increase collagen and GAG deposition and compressive properties	Gunja et al. [19]
TGF-β1	Meniscal fibrochondrocytes and articular chondrocyte	Monolayer culture	Increase SMA content	Zaleskas et al. [20]
TGF-β1	Articular chondrocytes	Explant culture	Reduce MMP-1, MMP-3, MMP-8, and MMP-13 expression and induced TIMP-2 and TIMP-3 production	Hui et al. [21]
TGF-β1	Articular chondrocytes	Monolayer culture	Suppress MMP-13, MMP-14 expression	Takahashi et al. [22]
TGF-β1	Human synovium-derived stem cells	Monolayer culture	Enhance chondrogenic differentiation and proliferation	Kim et al. [23]
TGF-β1	BMSCs	Monolayer culture	Enhances chondrogenic differentiation and proliferation	Jian et al. [24]
TGF-β	MSCs	Monolayer culture	Induce chondrogenic differentiation	Augustyniak et al. [25]—
				Tang et al. [26]
TGF-β1, TGF-β2, IGF-I	Dedifferentiated adult human articular chondrocytes	Monolayer culture	Reexpress aggrecan and type II collagen genes	Yaeger et al. [27]
TGF-β1	BMSCs	Chitosan/gelatin scaffolds culture	Promoted chondrogenic differentiation of MSCs, cartilage matrix synthesis, repair of rabbit cartilage defects	Diao et al. [28]
TGF-β3	BMSCs	PLGA-gelatin/chondroitin sulfate/hyaluronic acid hybrid scaffold in rabbit	Enhance MSCs proliferation and abundant ECM production, cartilage regeneration	Fan et al. [29]
TGFβ3	None	PCL-HA scaffold in rabbit	Regenerate articular cartilage by homing of endogenous cells	Bochyńska et al. [30]
TGFβ3 and CTGF	None	PCL scaffold in sheep	Lead to heterogeneous meniscus regeneration	Lee et al. [31]
BMP-2	Dedifferentiated articular chondrocytes	Monolayer culture	Reverse chondrocyte dedifferentiation	Gouttenoire et al. [32]
BMP-2	None	Intra-articular injection in mice	Enhance matrix turnover in native and IL-damaged cartilage	Davidson et al. [33]
BMP-2	Articular chondrocytes	Solvent preserved human meniscus explant culture	Stimulate chondrocytes migration and proliferation and enhance meniscus repair	Minehara et al. [34]
BMP-7	Articular chondrocytes	Monolayer culture	Counteract chondrocyte catabolism induced by proinflammatory cytokines	Elshaier et al. [35]
				Huch et al. [36]
BMP-7	None	Intra-articular injection in sheep	Fill meniscal defect with cellular fibrous tissue	Forriol et al. [37]
BMP-7	None	Injection into Achilles tendon in rats	Regenerate meniscus-like tissue	Ozeki et al. [38]
BMP-2/-4/-6	hBMSC	Monolayer culture	Enhance chondrogenic differentiation	Sekiya et al. [39]
BMP-2/-4/-6/ -7 and CDMP-1/-2	Articular chondrocytes	Alginate beads culture	BMP-7 are most potent in upregulating proteoglycan production and counteract catabolic activity mediated by IL-1	Chubinskaya et al. [40]
BMP-7 and TGF-β1	Synovial mesenchymal stem cells	Pellet culture	Enhance chondrogenesis from synovium-derived MSCs	Miyamoto et al. [41]
BMP-2/BMP-7, TGF-β1	Synovial tissue	Agarose scaffold culture	Enhance chondrogenic differentiation of synovial explants	Shintani and Hunziker [42]
bFGF	Meniscal fibrochondrocytes	Monolayer culture	Enhance proliferation	Hiraide et al. [43]
				Kasemkijwattana et al. [44]
bFGF	Meniscal fibrochondrocytes	PGA scaffold culture	Enhance proliferation	Stewart et al. [45]
bFGF	Meniscal fibrochondrocytes	Alginate scaffold culture	Enhance proliferation and SMA expression	Cucchiarini et al. [46]
bFGF	BMSCs	Monolayer culture	Enhance proliferation	Sotiropoulou et al. [47]
bFGF	MSCs	Monolayer culture	Maintain the multilineage differentiation potential of MSCs	Buckley and Kelly [48]—
				Martin et al. [49]
bFGF and hypoxia	Meniscal fibrochondrocytes	Three-dimensional pellet culture	Reexpress collagen type II and PGs gene	Adesida et al. [50]
bFGF	Intervertebral disc cells	Monolayer and alginate beads culture	Suppress proteoglycan production	Li et al. [51]
bFGF	Articular chondrocytes	Monolayer culture	Suppress collagen type II and decorin synthesis	Sonal [52]
bFGF	Articular chondrocytes	Monolayer culture	Upregulate MMPs, aggrecanases, nitric oxide and superoxide anion expression	Muddasani et al. [53]
bFGF	Articular chondrocytes	Alginate culture	Antagonizes proteoglycan synthesis	Loeser et al. [54]
bFGF	Articular chondrocytes	Gelatin-chondroitin-hyaluronan hybrid scaffold culture	Repair with hyaline-like cartilage	Deng et al. [55]
bFGF and hypoxia	Meniscal fibrochondrocytes	PLLA scaffold culture	Enhance GAGs production and compressive properties of constructs	Gunja and Athanasiou [56]
bFGF and TGF-β3	None	Electrospun PCL scaffolds culture	Improve meniscus repair and scaffold integration	Ionescu et al. [57]
IGF–1	Meniscal fibrochondrocytes	Alginate scaffold culture	Increase collagen and GAG synthesis as well as mechanical properties	Puetzer et al. [58]
IGF-1	Meniscal fibrochondrocytes	Monolayer culture	Enhanced proliferation and ECM formation	Tumia and Johnstone [59]
IGF-1	BMSCs	Monolayer culture	Modulate chondrogenic differentiation	Longobardi et al. [60]
IGF-1	Meniscal fibrochondrocytes	Explant culture	Stimulated cell migration	Bhargava et al. [61]
IGF-1	BMSC (transfection of hIGF-1 gene)	Intra-articular injection in goat	Promote the repair of full-thickness meniscal defects	Zhang et al. [62]
IGF-1	Articular chondrocytes; (transfection of hIGF-1 gene)	Polymerized fibrinogen in equine model	Enhance cartilage healing	Goodrich et al. [63]
IGF-1 and TGF-β1	BMSCs	Three-dimensional fibrin disk culture	Enhance chondrogenic differentiation	Worster et al. [64]
IGF-1 and TGF-β1	None	Explant culture	Improve repair of meniscus avascular zone	Izal et al. [65]
IGF–1, TGF-β1, bFGF	Fibroblast-like synoviocytes	PGA/PLLA scaffold culture	Enhance collagen type II and aggrecans expression	Fox et al. [66]
IGF and BMP-7	Articular chondrocytes	Monolayer culture	Suppress MMP-13 expression	Im et al. [67]
VEGF	None	VEGF-coated sutures in a sheep	Fail to promote meniscus healing	Petersen et al. [68]
HGF	Meniscal fibrochondrocytes; (transfection of HGF-1 gene)	PGA scaffold in mice	Induce blood vessel formation in engineered constructs	Hidaka et al. [69]
CTGF	Meniscal fibrochondrocytes	Fibrin glue in rabbits model	Promote healing of meniscal defect in the avascular zone	He et al. [70]
CTGF	None	Hydrogel collagen scaffold in rats model	Enhance articular cartilage regeneration	Nishida et al. [71]
PDGF-AB	Meniscal fibrochondrocytes	Monolayer culture	Increase proliferation and matrix formation	Tumia and Johnstone [72]
PRP	Meniscal fibrochondrocytes	Gelatin hydrogel in a rabbit model	Promote meniscus repair	Ishida et al. [73]