Cartilage and bone tissue engineering using adipose stromal/stem cells spheroids as building blocks

Table 1  In vitro and in vivo studies with adipose derived stem/stromal cells spheroids for cartilage and bone engineering

Tissue	Spheroid production method	Defect/Animal model	Main outcomes	Ref.
Cartilage	Spontaneous formation in 48-well plate	In vitro	Further optimization of chondrogenic induction will be required	[69]
Cartilage	Scaffold	Subchondral bone in Rabbit	The structure and function of regenerated tissue was similar to hyaline cartilage	[70]
Cartilage	Spinner flask	Transplanted subcutaneously in Mice	Spheroid culture is a viable method for chondrogenic differentiation and in vivo cartilage formation	[52]
Cartilage	Porous scaffold	Femur trochlea on the femoropatellar groove in Rabbit	Formation of mature cartilage in vivo	[71]
Cartilage	Micro-molded non-adhesive hydrogel	In vitro	The study confirms that spheroids mimic a stable cartilage tissue	[35]
Bone	Hanging droplet	Muscle pouch in femur in a Rat	Spheroids presented up-regulation of osteogenic markers, extracellular matrix mineralization and, when implanted in vivo, greater bone volume	[63]
Bone	Overlay	In vitro	Spheroids presented calcium deposits and cells were positive for CD31 (classic endothelial marker)	[72]
Bone	Pellet culture	Osteochondral (femoral trochlear groove) in microminipigs	Spheroids may induce regeneration of cartilage and subchondral bone	[73]
Bone	Agarose chip	Dorsal in Mice	Formation of ectopic bone	[74]
Bone	Elastin-like Polypeptide (ELP) and Polyethyleneimine (PEI) surface	In vitro	Spheroids showed superior osteogenic differentiation than monolayer culture. Spheroids produced bone extracellular matrix and presented greater mineralization	[64]
Bone	Centrifugation	In vitro	Composite spheroids enhanced expression of osteogenic genes and mineralization after fusion process	[75]
Bone	Non-adhesive surfaces	In vitro	Spheroids up-regulated osteogenic markers, showed low mineral production and produced osteocalcin protein	[65]