Table 2.

Meniscus explant models for injury repair and healing

Injury Model	Source	Treatment	Outcomes	Ref.
5-mm radial tears in the mid body of the whole meniscus including both the red-white and white-white zones.	Canine	ECM based decellularized scaffolds (dECM) with platelet-rich plasma (PRP)	Cell infiltration and proliferation enhanced by dECM and PRP in contrast to the suture-repaired defect only group by 40 days.	(16)
2-mm full thickness cylindrical defects in the whole meniscus	Canine	HGF and PDGF released from collagen sponge and collagen gel	Higher cell numbers around the defect after repair with collagen gel than with collagen sponge treated with HGF or PDG. HGF and PDGF delivery showed organized collagen formation after 4 wks.	(12)
4×2 mm cylindrical tissue was punched out from 8 mm disc and re-inserted back with tissue adhesives.	Porcine	Biodegradable block copolymeric tissue adhesives with collagenase	Significantly higher adhesive strength of new copolymer glue than fibrin glue. No improvement observed by collagenase treatment after 4 wks.	(27)
10-mm meniscal fragment: 5-mm longitudinal tears in central avascular zone	Human	Transplantation of meniscus cells transfected with 18 genes	Both juvenile and adult human meniscal fibrochondrocytes were safely transfected with nonviral genes. Transgenes expression was maintained for at least 5 days after seeding cells around the meniscal defect ex vivo. No tissue repair outcome was reported	(40)
Sliced strips with full-depth longitudinal incisions in avascular zone	Porcine	Sequential delivery of CTGF and TGF-β3	Fast release of CTGF, followed by TGF-β3 release resulted in seamless healing of avascular meniscus tears by stem cell recruitment in 8 wks.	(6)
			A high CTGF dose and slow TGF-β3 release are most effective for integrated healing of avascular meniscus.	(5)
4-mm cylindrical tissues punched out and reinserted into 8 mm disc from the outer 2/3 zone.	Porcine	Matrix Metalloproteinases (MMPs) inhibition	Enhanced tissue repair at the interface enhanced by inclusion of the broad-spectrum MMP inhibitor in presence of IL-1 in 2 wks.	(30)
Wedge-shaped nit explants prepared by radial cut; radial defect leaving 1mm gap	Bovine	Cells digested from meniscus with different duration of collagenase	Rapid dissociation in collagenase resulted in cells expressing a higher level of collagen type II expression than the overnight dissociation group over 8 wks. No difference in tissue healing between rapid and slow digestion.	(41)
2-mm cylindrical defects in the 5-mm thick radially cut meniscus strips.	Human	High mannuronic acid content (BioMVM) alginate spheres containing human meniscal fibrochondrocytes	Fibrochondrocytes encapsulated BioMVM alginate produced and retained significant amounts of proteoglycans in vitro for 21 days. Ex vivo culture for 3 dyas only showed the use potential of this system for meniscus tissue healing. Tissue healing outcome was not assessed here.	(31)
5×10 mm cylindrical disc punched out from the avascular zone of radially cut meniscus strips followed by a 2.5-mm cut along the long axis of the cylindrical disc.	Bovine	Adipose-derived stem cells (ASCs) seeded methacr ylated gelatin (mGL) hydrogels with TGF-β3	ASC-seeded hydrogels with preloaded TGF-β3 resulted in enhanced chondrogenic differentiation and improved healing with higher load to failure, stiffness, and Young modulus than control without TGF-β3 over 8 wks.	(32)
2×2 mm cylindrical hole in the intermediate zone	Caprine	Fresh chondrocyte (FC) isolates vs minced cartilage (MC) fragments loaded polyurethane scaffolds (Actifit®).	Both enzymatically isolated FC and MC showed improved matrix deposition and enhanced push-out strength after 4 wks compared with the acellular implant.	(37)
4-mm cylindrical defects	Bovine	Fibrin gel	Significantly higher cell migration in the red zone than in the white zone in response to injury. Migrating population is more similar to chondrogenic progenitor cells (CPCs) than other meniscus cells.	(33)
5×10 mm cylindrical disc punched out from the avascular zone of radially cut meniscus strips followed by around 2.5-mm cut along the long axis of the cylindrical disc.	Bovine	Meniscal fibrochondrocytes (MFC)-seeded electrospun nanofibrous scaffold wrapped around the defect	Improved healing by 8 wks through recruiting cells, and promoting their differentiation into defect site, and recovered mechanical properties up to 40% of native meniscus	(34)
4-mm full thickness cylindrical explants from outer two third zone were sliced into 1 to 2 mm thick tissue slices.	Bovine	Multiple growth factors on meniscus tissue with static mechanical compression	TGF-β1 was the most potent stimulator of both protein and proteoglycan production, whereas bFGF was the least effective stimulator among bFGF, IGF-I, PDGF, and TGF-β1 as revealed by 2 wks explant culture.	(29)
8-mm full thickness cylindrical defect from outer one third region with 4-mm core defects punched out and reinserted	Porcine	Application of interleukin-1 (IL-1) on the integrative repair of the meniscus	Explant culture over 4 wks time period showed exposure to IL-1α even for 1 day can significantly reduce cell accumulation, tissue repair and integration.	(35)
4-mm cylindrical defects in the avascular zone of the meniscus fragments.	Ovine	Fibroblast-like synoviocytes (FLS) seeded PGA/PLLA scaffolds with multiple growth factors (e.g. FGF, TGF-β1, IGF-1)	FLS-seeded scaffold constructs failed to integrate into avascular meniscal tissue even after 6 wks.	(36)
Full thickness (dimension not known) longitudinal defect into meniscus tissue fragments.	Human	Micropatterned methacrylated gelatin (Gel-MA) scaffold	Improved integration between the new tissue and the native meniscus tissue was observed with relatively poor tensile mechanical properties after 4 wks.	(44)
4-mm full thickness cylindrical defect made into 8-mm cylindrical explants from the inner and outer zones	Porcine	No treatment; Intrinsic repair response differences between the inner and outer zone	Repair strength and tissue integration increased significantly over time (6 wks) in both zones with no significant difference between the zones.	(38)
Whole meniscus with radial tear (size not reported) in the inner anterior horn	Rodent	Chondroprogenitor cells (CPCs), bone-marrow mesenchymal stem cells and SDF-1	Unlike BM-MSCs, CPCs do not undergo terminal hypertrophic differentiation during the tissue repair process. Like BM-MSCs, CPCs are responsive to the chemokine stromal cell-derived factor-1 (SDF-1) and they can promote tissue repair by migrating to the injured/damaged meniscal tissue through SDF-1/CXCR4 signaling pathway.	(50)
Longitudinal meniscal tear was created by a full length cut in the meniscus strips along the circumferential direction of the collagen bundles in the avascular zone.	Bovine	Human meniscus avascular cells seeded electrospun collagen scaffold	Collagen scaffolds showed no significant difference from defect only control, whereas cell-seeded collagen scaffolds led to improved tissue repair and integration after 3 wks.	(39)