Smart scaffolds in bone tissue engineering: A systematic review of literature

Table 2 Description of included studies which modified the scaffolds by addition of extracellular matrix molecules

Ref.	Scaffold	Fabrication	Type ofmodification	Cell type	Tests and results
Kim et al[43], 2006	BGNF + Col 1	Electrospinning process	Surface coating	MG63Cs	ALP activity: BGNF + Col 1 > Col 1
Lechner et al[44], 2006	β-TCP + F + T	-	New composition	BMMSCs	ALP activity: Increased during 28 d of culture FACS: CD 31: Increased expression by 100 folds
Turhani et al[34], 2007	HA + Col 1 + rhBMP-2	-	Surface coating	SaOS-2Cs	XTT proliferation assay: (relative) HA + col 1 + rhBMP-2: 1.5 Control: 0.5 ALP activity: HA + col 1 + rhBMP-2: 50 U/μg Control: 25 U/μg
Srouji et al[45], 2008	PCL + Col	Electrospun meshed scaffold	Electrospun nanofiber membrane	BMMSCs	Alamar Blue assay: PCL + Col = PCL [Data as mean ± SD (P < 0.05)] In vivo: Good integration after subcutaneous implantation
Hao et al[46], 2010	A: ADSCs-Col/PLGA-β-TCP B: Acellular Col/PLGA-β-TCP	Low- temperature deposition manufacturing (LDM) based on the layer-by-layer manufacturing principle of solid free-form fabrication	Surface coating	ADSCs	ALP activity: ECM mineralization in group A > group B Evident calcification level in group A, no apparent calcification in group B In vivo: Woven bone with a trabecular structure in group A No bone formation in group B
Xu et al[30], 2009	BG + Col-HYA-PS	Sol–gel method	New composite fabrication	BMMSCs	Cell attachment: Number of attached cells on BG + Col - HYA - PS was the highest Cell proliferation: BG + Col - HYA - PS > BG + Col and BG + Col - HYA > BG ALP activity: BG + Col - HYA - PS > BG + Col and BG + Col - HYA > BG
Kawai et al[47], 2009	OCP + Col	Mixing + lyophilization	Surface coating	MSST-2 Cs	Proliferation and attachment : OCP + Col > OCP (control) In vivo: OCP + Col: Enhanced bone regeneration ratio 83:17 generated maximum repair level of approximately 64% of the defect at 12 wk
Zhang et al[48], 2010	β-TCP + Col	Electrospun + impregnating methods	Architecture + surface coating	MG63Cs	MTT assay: (relative) β-TCP + Col: 0.30 Control (β-TCP): 0.25
Qu et al[49], 2010	C + HA + RGD peptide	In situ compositing hybridization + lyophilization	Surface coating	BMMSCs	Fluorescence microscopy: Cell adhesion rate: CS + HA: 54.7% C + HA + RGD peptide: 71.6% and 80.7% ALP activity: C + HA + RGD peptide: 0.00596 ± 0.00081 U/L per ng C + HA: 0.00283 ± 0.00025U/L per ng
Kang et al[50], 2011	Fi + HAH	The multi-head deposition system	Surface coating	ADSCs	ALP activity: Single day treatment: 0.5 mmol/mg No treatment: 0.5 mmol/mg Daily treatment: 3 mmol/mg
Marelli et al[51], 2011	nBG + DC	Plastic compression technique	Surface coating	MC3T3-E1 CS	Confocal microscopy of fluorescently: Attachment no difference ALP activity: nBG + DC: 3.5 × 105 Control (nBG): 2.5 × 105 Alamar blue assay: nBG + DC: 6.5 × 105 Control: 8 × 105
Phipps et al[52], 2011	PCL + Col I + nHA	Electrospun	Bone-mimetic electrospun matrices	BMMSCs	Activation of focal adhesion kinase: Cells seeded onto PCL/Col/nHA scaffolds were better spread, and exhibited greater amounts MTS assay: (relative) PCL + Col + nHA: 5 PCL + nHA: 2.5 PCL: 1
Weeks et al[53], 2012	PLLA + CXCL12, 13 + F + Col IV	-	Surface coating	BMMSCs	Antibody-blocking studies: Anti-α5β1 inhibits MSC attachment: PLLA + CXCL12, 13 + F + Col IV: 500 cells/mm2 PLLA + F + Col IV: 400 cells/mm2

BG: Bioglass; PLLA: Poly(l-lactic acid); Col: Collagen; C: Chitosan; PLGA: Poly(D,L-lactic-co-glycolic acid); PCL: Poly(e-caprolactone); HA: Hydroxy apatite; TCP: Tricalcium phosphate; HAH: Hyaluronic acid hydrogel; nBG: Nano-sized bioactive glass; BGNF: Bioactive glass nanofiber; OCP: Octacalcium phosphate; F: Fibronectin; Fi: Fibrin; nHA: Hydroxy apatite nano particles; CXCL: Chemokine ligand; T: Thrombin; rh: Recombinant human; BMP: Bone morphogenetic protein; HYA: Hyaluronic acid; PS: Phosphatidylserine; DC: Dense collagen; iH: Immobilized heparin; RGD: Arg-Gly-Asp; BMMSCs: Bone marrow mesenchymal stem cells; MG63Cs: Human osteosarcoma cells; SaOS-2 Cs: Sarcoma osteogenic cells; MC3T3-E1: Osteoblast precursor cells; ADSCs: Adipose-derived stem cells; MSST-2 Cs: Mouse bone marrow cells; ALP: Alkaline phosphatase; FACS: Fluorescent activated cell scan; XTT: Sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-2H-tetrazolium inner salt; MTT: 2-(4,5-dimethyl-2 thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide; MTS: 5-[3-(carboxymethoxy)phenyl]-3-(4,5 dimethyl-2-thiazolyl)-2-(4-sulfophenyl)- 2H-tetrazolium inner salt; CD: Cluster of differentiation.