Table 3.

Overview of the studies performed on bone regeneration and distraction osteogenesis using ASC.

Author	Cell type	Scaffold	Model	Observation
ASC's application with scaffolds, without the use of growth factors
Yoon et al. [200]	ASC & d-ASC	PLGA	Calvarial CSD in rats	d-ASCs with PGLA have better bone regeneration capability in CSD than constructs with ASC alone
Cui et al. [201]	ASC	Coral	Calvarial CSD in dogs	Bone was almost completely restored in the CSD, when ASCs were applied. Minimal bone formation with fibroid tissues was observed in the control group
Carvalho et al. [202]	ASC	SPCL	Calvarial CSD in mice	Nondifferentiated human ASCs enhance ossification of nonhealing mice CSD
Schubert et al. [203]	d- ASC	3D osteogenic ASC	(1) Four-level spinal fusion in pigs (2) Femur CSD in pigs	In a spine fusion model, applying 3D d-ASC demonstrated a significant increase in bone formation In the femoral CSD model, the 3D d-ASC achieved new bone formation and fusion in a poorly vascularized fibrotic environment
Liu et al. [204]	Al- ASCs, Au-ASC	Coral	Cranial CSD in dogs	Allo-ASC transplantation did not induce a systemic immune response and was able to repair the cranial CSDs in an analogous way to that of the autologous cells
Cowan et al. [205]	ASC	PGLA	Calvarial CSD in mice	ASC showed a significant intramembranous bone formation by 2 weeks and complete bridging by 12 weeks without any additives
Di Bella et al. [206]	ASC, d-ASC	PLA & FPLA	Skull CSD in rabbits	(1) FPLA as a fibronectin-coated scaffold promotes bone formation more than using PLA alone (2) d-ASCs combined with FPLA enhance bone formation significantly when compared with ASC alone
Lendeckel et al. [207]	ASC	Fibrin glue & bone graft	Cranial CSD in a 7-year-old girl	Complete calvarial healing after 3 months
Nomura et al. [208]	ASC	Collagen gel	DO femur in rats	ASC promoted bone formation in the distracted callus and shortening the consolidation phase
Sunay et al. [209]	ASC, d-ASC		DO tibia in rabbits	d-ASC showed increase in the callus density and the ossification rate compared to the undifferentiated ASC. The quality of bone formed within the callus was significantly enhanced. Use of d-ASC can shorten the consolidation period of distraction osteogenesis
Arrigoni et al. [210]	ASC	HA	Tibia CSD in rabbits	ASCs-HA constructs improved bone healing significantly, when compared to using scaffold alone
Cheng et al. [211]	ASC	DBM	Calvarial CSD in rabbits	New bone formation was documented in bone defects transplanted with DBM-ASCs composites
ASC's application with scaffolds, with the use of growth factors like BMP2 and TGF (β3)
Lin et al. [212]	BMP2 expressing ASC and TGF (β3)	PLGA or gelatin sponge	Calvarial CSD in rabbits	Gelatin sponges and apatite coated PLGA were compared as scaffolds. Gelatin scaffold stimulated the bone healing more than apatite coated PLGA, regardless of BMP2 or TGF-β3 expression. The ASCs/gelatin expressing BMP2 triggered better bone healing than ASCs/gelatin expressing TGF-β3
Peterson et al. [213]	HPLA, with BMP-2 carrying adenovirus	CCC	Femur CSD in rats	HPLA cells genetically modified by adenoviruses, overexpressing BMP-2, can induce bone formation in vivo and heal CSD in rat femurs
Levi et al. [214]	Human ASC, with BMP-2	PGLA	Calvarial CSD in mice	(1) Human ASCs ossify CSD without the need for predifferentiation (2) rBMP-2 was observed to increase human ASC osteogenesis in vitro and osseous healing in vivo

GF:growth factor, PLGA: polylactide-co-glycolic acid, d-ASC: differentiated ASC, PLA: polylactic acid, SPCL: wet-spun starch polycaprolactone, Allo-ASC: allogeneic ASC, Au-ASC: autologous ASC, FPLA: fibronectin-treated PLA, HPLA: human processed lipoaspirate, CCC: collagen-ceramic carrier, HA: hydroxyapatite, and DBM: demineralized bone matrix.