Table 1. Synthetic Bone-Cartilage Scaffolds Manufactured Using Various Techniques and Biomaterials^a.

Study	Materials for bone	Materials for cartilage	Scaffold design	Fabrication methods	Mechanical properties (compressive)	Biological aspect
(24)	PCL with SAPH	PCL with SAPH	Monolithic	AM (FDM)		In vivo study for 3% SAPH-coated PCL-scaffold showed cell proliferation and osteogenic differentiation.
(17)	PLGA with nano-HA	PLGA with nano-HA	Monolithic	Thermally induced phase separation, annealing and freeze-drying	EM: 0.55 MPa	Higher viability and proliferation of MSCs as compared to PLGA suggested potential use for the cartilage repair in clinical application.
(177)	Agarose hydrogel with HA	Agarose hydrogel with HA	Monolithic	Casting	EM: 4.3 kPa	Hydrogel-ceramic composite was cultured using chondrocytes that showed optimal mineral aggregate size and content of the native tissue interface.
					Shear modulus: 8.7 kPa
(23)	Chitosan-Gelatin-HAc with GR	Chitosan-Gelatin-HAc	Monolithic (Two types)	3Dbioprinting	EM 0.06% GR: 8 MPa	Biocompatibility test under interaction with P3 BMSC.
					EM 0% GR: 4 MPa
(120)	PLGA with nano-HA	PLGA	Bilayered	Casting and sintering	Bony-layer EM: 142 MPa	High cell viability for the cell analysis with rabbit chondrocytes and BMSCs.
					Cartilage-layer EM: 62 MPa
					Combined EM: 85 MPa
(121)	PLGA-PEG foam	PGA-nonwoven mesh	Bilayered			Seeding each layer of PLGA-PEG foam and PGA separately with periosteal cell and chondrocyte for 1-week (immature) as compared to 4-week (mature) construct demonstrated better cartilage/bone integration.
(115)	PCL with HA	PGA/PLA	Bilayered	AM-FDM	Bony-layer EM: 58 MPa	Successful femoral head tissue regeneration of mice.
					Cartilage-layer EM: 5 MPa
(116)	PCL with PDO-nanospheres	PEG-hydrogel with PLGA-nanospheres	Bilayered	Casting and UV-light irradiating	Bony-layer EM: 22 MPa	Improved human MSC adhesion in differentiation to the artificial layers as compared to pure PCL-scaffold.
					Cartilage-layer EM: 6 MPa
(118)	PLA with G5 bioglass	PLA	Bilayered	AM	Bony-layer EM: 44 MPa	Addition of G5 bioglass lead to a higher vascularization of the implant and consequently promoted bone regeneration.
					Cartilage-layer EM: 28 MPa
(170)	PVA-NOCC (hydrogel) with HA	PVA-NOCC (hydrogel)	Bilayered	Tissue harvesting, casting and freezing		In vivo biocompatibility test using of a rat model showed that the bilayered construct may have a promising potential for osteochondral defect.
(171)	HA with polyamide6	PVA	Bilayered	Freezing-thawing and high-temperature annealing		The evaluation of bilayered scaffolds for biocompatibility, osteogenesis and chondrogenesis using ectopic osteochondral construct showed potentials for in situ osteochondral defect repair.
(172)	polyHEMA(38)-hydrogel with HA	polyHEMA(200)-hydrogel with HAc	Bilayered	Sphere-templating and freeze-drying	Dry EM: 39 MPa	Cyto-compatibility test with human MSCs and chondrocytes
					Wet EM: 0.09 MPa
(178)	Plasmid BMP-2-activated chitosan-gelatin with HA	Plasmid TGF-β1-activated chitosan-gelatin	Bilayered	Casting, salt-leaching and freeze-drying		Spatially controlled and localized gene-activated bilayered scaffold showed significant cell proliferation and induced cell differentiation for in vitro results of the rabbit knee osteochondral defect model.
(15)	Silk fibroin with CaP	Silk fibroin	Bilayered	Salt-leaching and freeze-drying	EM: 0.4 MPa	In vitro tests of rabit bone MSCs supported cell attachment, viability and proliferation in interaction with the scaffold.
(138)	Agar scaffold	PEGDA with HA	Bilayered	Casting and UV-light irradiating	EM: 145 kPa	The presence of HA increased interfacial shear strength of the scaffold as early as 7 days of in vitro tissue culture enhancing the integration of engineered cartilage to bone.
					Shear strength: 5.9 kPa
(30)	PLGA microsphere scaffold	Alginate hydrogel	Multilayered (3 layers)	Sintering and freeze–thawing	EM: 7.8 MPa	The multiphasic scaffold exhibited superior tissue repair efficacy in a rabbit knee defect model with a gradient transition and integration between cartilage-bone tissue. However, after decellularization the tissue repair efficacy of the graft decreased, remaining challenges for the industrialization of the graft.
(14)	Deep zone: Collagen type-I with HA	Intermediate zone: Collagen type-I and II with HA	Multilayered (3 layers)	Freeze-drying		The Scaffold in a critical-sized defect was tested in vivo in a rabbit knee.
		Superficial zone: Collagen type-II with HAc				The results showed that it was able to guide the host reparative response leading to tissue regeneration with a distinct zonal organization.
(173)	Silk fibroin with HA	Silk fibroin	Multilayered (3 layers)	Paraffin-sphere leaching and thermally induced phase separation	Bony-layer EM: 55–110 kPa Cartilage-layer EM: 52–84 kPa	Good biocompatibility results of the multiphasic scaffold supported cell growth and differentiations toward chondrocytes and osteoblasts. Particularly, it showed that the intermediate layer can play a role in preventing mixing cells with each other within the chondral and the bony layers.
(174)	Chitosan with HA	Chitosan-Silk fibroin	Multilayered (4 layers)	Temperature gradient processing	Full scaffold EM: 150 kPa	14 days cell culture showed that the scaffolds were able to well support the growth and infiltration of cells, suggesting a promising potential for articular cartilage repair.
					Bone-layer EM: 260 kPa
(117)	PCL-β-TPC composite	PCL	Gradient	Hybrid extrusion and electrospinning	Only tensile tests, no compressive tests.	The graded scaffold showed better distributions of various biological factors, including the concentrations of drugs/growth factors, and biodegradation rate required for fabricating complexity of the native tissue.
					EM: 18.5–27.5 kPa
					UTS: 810–1080 kPa
(180)	GelMA-GG-hydrogel with HA	GelMA-GG-hydrogel	Gradient	Casting and freeze-drying		The cell culture results of the graded scaffold showed an upregulation of the prevasculature formation in the bone-like region while it was downregulated in the cartilage-like region.
(22)	PNAGA-hydrogel with monomer	PNAGA-hydrogel	Gradient	AM (bioprinting)	EM compressive: 20–137 kPa	The in vivo animal evaluation of biohybrid gradient hydrogel scaffold showed simultaneous regeneration of both cartilage and subchondral bone within osteochondral defects.
					EM tensile: 20–43 kPa
					Max. tensile strength: 0.41 MPa
					Max. compressive strength: 137 MPa
(179)	PACG-GelMA-hydrogel with bioactive glass	PACG-GelMA-hydrogel with Mn2+	Gradient	AM (bioprinting)	EM compressive: 837 kPa	In vitro biological experiment and in vivo implantation showed that the biohybrid gradient hydrogel scaffold can facilitate the concurrent regeneration of subchondral bone and cartilage in a rat model.
					EM tensile: 320 kPa
					Max. tensile strength: 1.1 MPa
					Max. compressive strength: 12.4 MPa
(182)	Collagen with HA	Collagen	Gradient	Casting and diffusion

^aThe acronyms summarized in this table are PCL = polycaprolactone, SAPH = self-assembling peptide hydrogel, FDM = fused deposition modeling, PLGA = poly(lactide-co-glycolide) acid, HA = hydroxyapatite, EM = elastic modulus, HAc = hyaluronic acid, GR = graphene, PEG = polyethylene glycol, PGA = polyglycolic acid, PDO = poly(dioxanone), PLA = polylactic acid, UV = ultraviolet, PVA = poly vinyl alcohol, NOCC = N,O-carboxymethylated chitosan, HEMA = hydroxyethyl methacrylate, PEGDA = poly(ethylene glycol) diacrylate, CaP = calcium phosphate, TCP = tricalcium phosphate, GelMA = methacrylated gelatin, GG = gellan gum, PNAGA = poly(N-acryloyl glycinamide), PACG = poly(N-acryloyl 2-glycine), Mn²⁺ = manganese ions, FDM = fused deposition modeling, MSCs = mesenchymal stem cells, BMSCs = bone marrow stem cells.