Bioinks for bioprinting functional meniscus and articular cartilage

Figures & data

Figure 1. Factors affecting printability.

(A) The biofabrication window, finding a balance between printability and biocompatibility [85]. Reproduced with permission of Springer. (B) Graph depicting the shear-thinning behavior (viscosity decreasing with shear rate) of a gellan gum–alginate bioink [86]. Reproduced with permission from John Wiley & Sons Inc. (C) Extrusion of gelatin–alginate strand illustrating printability, with undergelation resulting in a droplet morphology and a lattice with truncated corners, ideal-gelation results a smooth uniform strand with square lattice and overgelation results in an inconsistent strand thickness [82] © IOP Publishing. Reproduced with permission. All rights reserved.

Figure 2. Bioprinting various bioinks.

(A) Composite printing of multimaterial methacylated bioinks printed through a photopermeable lumen resulting in (i) a core–shell when both inks are extruded and the UV is switched on, heterogeneous structure when each ink is extruded simultaneously and a hollow structure (ii) the respective confocal image of cells labeled with different dyes with cross-section insert [119]. Reproduced with permission from John Wiley & Sons Inc. (B) Overhanging structures printed with agarose into a fluorocarbon bath [120]. (C) Alginate sulfate–nanocellulose bioink printed into the shape of an ear [121]. Reproduced with permission of Springer. (D) Sheep meniscus shape printed with collagen type I and seeded with fibrochondrocytes [102]. Reprinted with permission from ACS Biomaterials Science & Engineering. Copyright 2016 American Chemical Society. (E) Tubular 5% PEGDA Schematic printed on a rotating rod in a photopermeable capillary [119]. Reproduced with permission from John Wiley & Sons Inc.

Figure 3. Advanced bioinks.

(A) (i) Elastic, highly stretchable of PEG-alginate-nanoclay printed in a bilayer mesh is stretched to three-times of its initial length followed by relaxation that demonstrates almost complete recovery of its original shape. (ii) A printed pyramid of the same material undergoes a compressive strain of 95% and returns to its original shape [172]. Reproduced with permission from John Wiley & Sons Inc. (B) (i) Setup of continuous multimaterial deposition in which seven different bioinks can be extruded simultaneously or alone by controlling the valve opening, (ii) printed helix and lumen structure using three different materials and a seven-material fiber [179]. Reproduced with permission from John Wiley & Sons Inc. (C) (i) Extrusion of decellurized ECM bioink alone and in conjunction with a PCL frame, (ii) live–dead staining depicting the cell viability after deposition, (iii) a scanning electron microscope image illustrating the ECM between the PCL fibers. Reprinted by permission from Macmillan Publishers Ltd, Nature Communications [177] © 2014.

ECM: Extracellular matrix; IPN: Interpenetrating network; PCL: Polycaprolactone; PEG: Polyethylene glycol.

Table 1. Bioinks specifically targeted toward articular cartilage repair.

Bioink	Reinforced	Cross-linking mechanism	Printability analysis	Shape	Biofabrication technique	Cell type	Viability
PEGDMA [92]	No	UV	No	Filled an in situ chondral defect	Inkjet	Human chondrocytes	Yes–no quantification
PEG–gelMA [180]	No	UV	No	Cylinder	Inkjet	Human BMSC	85%
Alginate alginate–Cs alginate-CsHA [139]	No	CaCl2 + UV	Yes (shear rate and viscosity)	Geometrical shapes	Extrusion	BMSC	>85%
GelMA alginate [181]	Yes (PCL)	Temperature CaCl2	No	Cylinder	Melt electrowriting	Human chondrocytes	80%
Collagen I [182]	Yes (PCL)	Temperature	No	Humeral head	Extrusion	–	–
Gelatin–fibrinogen–HA–glycerol [153]	Yes (PCL)	Temperature + thrombin	No	Cube, ear, bone defect, muscle	Extrusion	Human AFSC, rabbit CC, mouse myoblast	91–97%
Alginate [183]	Yes (PCL)	CaCl2	No	Lattice cube	Extrusion	Human chondrocytes	Yes–no quantification
Alginate HA–collagen I [143]	Yes (PCL)	Temperature	No	Cylinder	Extrusion	MSC	No
GelMA Alginate Agarose PEG [63]	Yes (PCL)	UV CaCl2 Temperature	Yes (line spreading ratio)	Lattice cylinder	Extrusion	Porcine BMSC	Yes 80%
GelMA–gellan gum [80]	No	UV	Rheology and effect of bioink concentration	Lattice	Extrusion	Equine CC	–
Collagen type II [107]	No	pH and temperature	No	Cylinder	Extrusion	Rabbit chondrocytes	Yes–no quantification
Silk–fibroin Silk–gelatin [184]	No	Tyrosinase	Rheology	Square lattice	Extrusion	Human chondrocytes	Yes–no quantification
GelMa–PEGDA–graphene oxide [117]	No	UV	No	Lattice cylinder	Laser	Human MSC	No
Methacrylated PEG–HA PEG-Cs [161]	No	UV	Rheology	Lattice	Extrusion	Equine CC	85%
Fibrinogen–collagen type I [185]	Yes (PCL)	Thrombin and temperature	No	Square	Inkjet	Rabbit CC	No
Gellan gum–alginate–cartilage particles Gellan gum–alginate–HA [86]	No	Strontium chloride	Rheology	Nose Ear Dogbone Meniscus	Extrusion	Bovine chondrocytes	80%
Decellurized cartilage [177]	Yes (PCL)	Temperature and pH	Rheology	Square lattice	Extrusion	Human ADSC	>95%

ADSC: Adipose tissue stem cell; AFSC: Amniotic fluid-derived stem cell; BMSC: Bone marrow stem cell; CC: Chondrocyte; Cs: Chondroitin sulfate; CsHA: Chondroitin sulfate hyaluronic acid; GelMA: Methacrylated gelatin; HA: Hyaluronic acid; MSC: Mesenchymal stem cell; PCL: Polycaprolactone; PEG: Polyethylene glycol; PEGDA: Polyethyleneglycol diacrylate; PEGDMA: Polyethylene glycol dimethacrylate.

Table 2. Bioinks specifically targeted toward meniscus repair.

Bioink	Reinforced	Cross-linking mechanism	Printability analysis	Shape	Biofabrication technique	Cell type	Viability
Alginate [186]	No	CaSO4	Determined the error from design to printed	Meniscus from scan	Extrusion	Bovine chondrocytes	94%
Alginate–acrylamide–acrylated urethane [187]	Yes (acrylated urethane)	UV	Viscosity analysis	Dog bone and basic meniscus shape	Extrusion	Acellular	–
PCL [66]	Yes (PCL)	–	No	Meniscus from scan	Extrusion	–	–
Collagen type I [104]	No	Temperature	Determined the error from design to printed	Meniscus from scan	Extrusion	Bovine fibrochondrocytes	Yes–no quantification
GelMA Alginate Agarose PEG [63]	Yes (PCL)	UV CaCl2 Temperature	Yes (line spreading ratio)	Lattice cylinder	Extrusion	Porcine BMSC	Yes 80%
Nanocellulose–alginate [168]	No	CaCl2	Rheology	Meniscus	Inkjet	Human nasal chondrocytes	∼70%
Gellan gum–alginate–cartilage particles Gellan gum–alginate–HA [86]	No	Strontium chloride	Rheology	Meniscus Nose Ear Dogbone	Extrusion	Bovine chondrocytes	80%
Alginate–PLA nanofibers [188]	Yes (PLA)	CaCl2	No	Lines Medial meniscus	Extrusion	Human ADSC	Yes–no quantification

ADSC: Adipose tissue stem cell; BMSC: Bone marrow stem cell; GelMA: Methacrylated gelatin; HA: Hyaluronic acid; PCL: Polycaprolactone; PEG: Polyethylene glycol; PLA: Polylactic acid.

Figure 4. Polycaprolactone printing.

Printing of anatomically accurate (A) meniscus embedded with PLGA beads that spatially released either TGF or CTGF to the inner and outer regions, respectively [66]. Reprinted with permission from AAAS and (B) a humeral head fabricated to facilitate cellular homing, which was implanted into a rabbit model [182]. Reprinted from The Lancet © 2010, with permission from Elsevier. (C) A reinforced osteochondral plug with spatially distributed bioinks of HA and atelocollagen for cartilage and bone regeneration [143] © IOP Publishing. Reproduced with permission. All rights reserved. (D) composite reinforced alginate bioink for endochondral tissue engineering printed in the shape of vertebrae, which supported mineral deposition and vasculature [13]. Reproduced with permission from John Wiley & Sons Inc.

HA: Hyaluronic acid; PLGA: Poly(lactic-co-glycolic acid).

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