Table 2.

Fabrication methods for large cartilage tissue engineering and regeneration therapies in pre-clinical and translational stages

Fabrication Method	Example	Strengths	Weaknesses	Study
Molds	MicroCT and MRI scans used to create custom injection molds for anatomical ovine meniscal cell-seeded alginate meniscus	• Retained native shape through 8 weeks of culture • GAG, Collagen, and Modulus increased with time in culture	• Equilibrium modulus half of native at 8 weeks • Heterogeneous matrix accumulation in center of constructs	Ref. 57
	MicroCT scans used to create custom molds for anatomical porcine MSC-seeded hyaluronate hydrogel femoral head cartilage	• Retained native shape through 12 weeks of culture • GAG and dynamic/equilibrium modulus increased with culture time	• Decreased modulus and cell viability at center of constructs • Integration to subchondral bone not addressed	Ref. 63
3D Bio-Printing	Extrusion bioprinting of biphasic alginate hydrogels with human chondrocytes and MSCs for osteochondral repair	• Distinctive cartilage-like and bone-like tissue formation seen in respective compartments after 3 weeks in vitro and 6 weeks subcutaneous in immunodeficient mice	• Max compressive modulus ~15 kPa • Limited printing height achieved	Ref. 141
	Melt-electrospinning writing of PCL scaffolds infused with gelatin-methacryloyl hydrogel encapsulating human chondrocytes	• Max compressive modulus of 400 kPa with 7% PCL fibers by volume, stress strain curve similar to cartilage • Increased aggrecan and COL1A1 mRNA in compressed constructs	• Cell viability <80% after 7 days in culture • No differences in protein with compression	Ref. 80
Woven	Woven PCL hemispherical scaffolds embedded with IL-1Ra lentiviral vector and seeded with human adipose-derived stem cells	• Uniform tissue growth, cartilage biomimetic properties, maintained anatomy after 28 d culture • Robust expression of IL-1Ra prevented MMP activity • Aggregate compressive modulus ~1000 kPa	• Slow scaffold resorption time • High polymer volume occupancy	Ref. 61
	Woven aligned collagen threads forming interdigitated arcade structure with macropores filled with MSC pellets, sandwiched between 2 collagen sheets, crosslinked	• Max compressive modulus of 1330 kPa after 28d culture, similar to human cartilage • Excellent fatigue resistance and elastic recoil • Increased GAGs and COL II content with culture time	• Poor integration of pellet with collagen threads • Weave pattern blocks lateral fusion of pellets	Ref. 142
Modular	BioCartilage (Arthrex) dessiccated particulated cartilage allograft hydrated with PRP and loaded into defect following microfracture	• Improved cartilage repair histology scores compared to microfracture controls in an equine cartilage defect • Arthroscopic administration, 13 month in vivo results	• Distal lesions showed no improvement • Sclerosis in all defects	Ref. 64
	Modular engineered tissue surfaces with self-adhesion of 4 mm agarose gel cylinders with juvenile bovine chondrocytes framed in a custom tibial plateau basket	• Robust bond between modules by 21 days in culture, 3D topography maintained • Compressive modulus and GAG content increase with culture time • No negative impacts with increased total size	• Fibrous tissue at module bonds • Equilibrium modulus ~40–60 kPa	Ref. 143