Table 1.

Summary of the recent studies on microscale/nanoscale materials used for the fabrication of cartilage tissue engineering (TE) structures.

Microscale/ nanoscale material type	Microscale/ nanoscale material application	Base material	Scaffold used	Cell type	In vivo	Major result	Ref.
Microspheres	The increase in the proliferation rate of MSCs and their chondrogenic differentiation.	Gelatin	Gelatin microsphere	Human BMSCs	—	Culturing MSCs on gelatin microspheres accelerated proliferation rate and preserved stemness properties as well as enhanced chondrogenesis	[31]
Microspheres	Delivery of rapamycin	PLGA	—	Human chondrocytes	Mice model	Provided sustained and controlled release of rapamycin for several weeks and prevented OA-like changes in chondrocytes under genomic and oxidative stress conditions	[29]
Microspheres	Verteporfin delivery	Chitosan	Collagen I-coated culture dish and PDMS substrates	Human chondrocytes	Mice model	Provided a local sustained release of verteporfin and significantly maintained cartilage homeostasis in a mice OA model	[72]
Microspheres	Microencapsulation of human osteoarthritic chondrocytes (hOACs)	Collagen	Collagen scaffold	hOACs	—	Collagen microspheres, as a screening platform, better maintained the hOAC phenotype compared with the 2D monolayer and 3D pellet cultures	[73]
Microspheres	As a scaffold	Cartilage	Cartilage microspheres	Rabbit MSCs	—	Induced the in vitro chondrogenesis without adding any serum or induction components	[74]
Nanocapsules	Celecoxib delivery	HA	—	—	Rat model	Spherical shape, high entrapment efficiency (97.98%), prolonged drug release, and improved histopathology analysis	[65]
NPs	Delivery of SM	PLGA	—	—	Rat model	Increased the chondroprotective effects of SM	[68]
NPs	KGN delivery	PLGA	m-HA	—	Porcine model	Improved hyaline cartilage and subchondral bone repair and demonstrated better therapeutic efficacy in full-thickness chondral defects	[71]
NPs	Melatonin delivery	Albumin	PCL scaffold	Human chondrocytes	—	Prolonged the drug release for 22 days and increased GAG deposition	[75]
Nanotubes	Cartilage repair	Carboxylated SWCNTs	SWCNTs/BSA/collagen composite scaffold	BMSCs	Rabbit model	Had no cytotoxic effect on BMSCs, improved mechanical properties and cell proliferation, and repaired cartilage defects in a rabbit model	[76]
Electrospun nanofibers	Scaffold fabrication	ECM/PCL hybrid	Cartilage-derived ECM/PCL composite	Rabbit chondrocyte	Mice model	Considerably promoted the proliferation of chondrocytes in vitro and facilitated the regeneration of cartilage in vivo	[77]
Electrospun nanofibers	Fabrication of a biocompatible scaffold	PLA/gelatin	CS-modified nanofibers	Rabbit BMSCs	Rabbit model	Had appropriate mechanical properties and suitable biocompatibility, showed better chondrogenic differentiation and promoted cartilage regeneration	[78]
Electrospun nanofibers	Fabrication of scaffold	PLLA	The PLLA/PDA/CS membranes	Rabbit chondrocytes/rabbit BMSCs	Rabbit model	Considerably facilitated the filling of the defect site and the generation of hyaline-like cartilage in vivo	[79]
Electrospun nanofibers	Scaffold fabrication	PCL/PEO	PCL/PEO combined with MSCs-derived TE construct	Rabbit synovial stem cells	Rabbit model	Significantly prevented meniscal extrusion, exerted a chondroprotective effect, and repaired meniscal defects	[80]
Nanocapsules	Delivery of TGF-β1	Gelatin and iron oxide	—	ATDC5 cells	—	Magnetic gelatin nanocapsules improved the differentiation of ATDC 5 cells with the increased expression of Col2a1 and aggrecan	[81]
Nanocrystal– polymer particles	Delivery of p38α/β MAPK inhibitor	PLA	—	Human OA synoviocytes	Mice model	Were non-toxic to cultured human OA synoviocytes, exhibited good retention in the joint and adjacent tissues, and also decreased inflammation and joint degradation	[67]
Nanofibers	Fabrication of collagen-like nanorods	Chitosan and polydiisopropyl fumarate	Fumarate copolymer– chitosan crosslinked nanofibers	Rat BMPCs/rat chondrocytes	—	Supported cell attachment and growth, as well as promoted both osteogenic and chondrogenic differentiation	[82]
NPs	Delivery of curcuminoid	HA/chitosan	—	Rat chondrocytes	Rat model	Provided prolonged release of curcuminoid, inhibited NF-kB signaling and the expression of MMP-1 and MMP-13, and upregulated the expression of type-II collagen in chondrocytes in vitro, as well as reduced the Outerbridge classification and Mankin pathological scores in a knee OA model	[69]
Nanogels	Encapsulation of TGF-β3	Alginate	—	hMSCs	—	Significantly reduced burst release, provided the sustained release of TGF-β3, and also resulted in better chondrogenic differentiation of hMSCs	[83]
Nano- composites	Fabrication of scaffold	PLDLA/HAp	PLDLA/HAp enriched with sodium alginate	—	Rabbit model	Improvement in articular cartilage defect treatment	[84]
Dendrimer	Delivery of KGN	PEGylated PAMAM	—	BMSCs	Rat model	KGN-PEG-PAMAM conjugate could induce higher expression of chondrogenic markers	[85]
NPs	Providing high RGD surface density	Gold	—	hMSCs	—	Had a promotive effect on cartilaginous matrix production and marker gene expression	[86]
Dendrimers	Providing a surface for cell attachment	PAMAM	A PAMAM surface with fifth-generation (G5) dendron structure.	hMSCs	—	Affected the expression of type-II and type-X collagens via effects on cell aggregate behavior	[87]
Magnetic NPs	Labeling of chondrocytes	Iron oxide	Collagen-chitosan/PLGA	Rabbit chondrocytes	—	Magnetic nanoparticles did not affect the cell phenotype and provided a technique for tracking cartilage regeneration and osteochondral defect repair	[88]
Nanofibers	Fabrication of nanofiber-based scaffold	PLGA	PLGA	hMSCs	—	Induced MSC differentiation into bone and cartilage	[89]
Nanofibers	Fabrication of scaffold	PLLA-PCL- collagen	PLLA-PCL- collagen/HA	Rabbit MSCs	—	Promoted orientation, adhesion and proliferation of BMSCs as well as expression of chondrogenic markers	[90]
Magnetic NPs	Physical stimuli	Magnetic NPs isolated from Magneto- spirillm sp.	Micromass culture system used	hMSCs	—	Enhanced the level of sulfated glycosaminoglycan (GAG) and collagen synthesis,and facilitated chondrogenic differentiation	[91]
NPs	KGN delivery	Chitosan	—	hMSCs	Rat model	Provided the sustained release of KGN and induced higher expression of chondrogenic markers	[92]
NPs	Co-delivery of Cbfa-1-targeting siRNA and SOX9 protein	PLGA	—	hMSCs	Mice model	Highly expressed chondrogenesis-related extracellular matrix (ECM) components	[93]
Nanofibers	Fabrication of electrospun embedded nanocomposite.	PLLA	PEG-POSS/PLLA	hMSCs	—	hMSCs were able to attach, proliferate, and differentiate into chondrocytes	[94]
NPs	Delivery of pDC316-BMP4-EGFP Plasmid	PLGA	PLLGA	Rabbit ADSCs	Rabbit model	BMP-4 plasmid could be successfully delivered into ADSCs by PLGA nanoparticles and promoted in vitro and in vivo chondrogenesis	[95]
Electrospun nanofibers	Fabrication of scaffold.	PCL	PCL	Human MenSCs	—	Induced chondrogenic differentiation of menstrual blood derived stem cells	[96]
NPs	TGF-β1 gene delivery.	Calcium phosphate	Collagen/chitosan	Rat MSCs	—	Could successfully induce MSC chondrogenic differentiation	[97]
Nanotubes	Providing titanium dioxide (TiO2) based surface.	TiO2	TiO2 nanotube	Limb mesenchymal cells	—	Could support chondrocytic functions	[98]
Nanofibers	Fabrication of scaffold.	PLLA	PLLA	hMSCs	—	Expressed cartilage-specific gene and formed typical cartilage morphology	[99]
Nanofibers	As scaffold	PCL	PCL	hMSCs/pig chondrocyte	Swine model	Showed the most complete repair, generated hyaline-like cartilage tissue, and had the highest equilibrium compressive stress (1.5 MPa) in the regenerated cartilage	[100]