Table 1.

In vitro studies using B-vitamins-based regenerative therapies.

Target Tissue	Compound	Method	Specie	Cell Line	Results	Ref.
Musculoskeletal regeneration	SrFO	SrFO-functionalized Ti substrates	Murine	Primary MSCs	Promoted cell adhesion, proliferation and osteogenic differentiation of MSCs	[15]
		SrFO-loaded biohybrid scaffolds	Human	Dental pulp human MSCs	Enhanced osteogenic related gene expression and osteogenic differentiation	[16]
	SrFO and CaFO	Sr- and Ca-based folates	Human	HOBs	Overexpression of ALP activity	[17]
	Folic acid	Hydroxyapatite nanoparticles loaded with FA	Human	Human MSCs	Overexpression of ALP activity and Runx2 gene (osteogenic differentiation)	[18]
		Vancomycin release from folic acid/ZnO quantum dots sealed titania nanotubes	Bacteria	Staphylococcus aureus	Prevented Ti implants-associated bacterial infections	[19]
	PABA	PABA doped micro-grooved carbon fibers	Murine	L929 and MC3T3-E1	Promoted the adhesion and proliferation of pre-osteoblasts with minimized cytotoxicity	[20]
	Riboflavin and derivatives	Free riboflavin and its derivatives	Murine	MC3T3-E1	Promoted osteoblastic differentiation, enhancing the effects of the typical inductors	[21]
	Nicotinamide	Free nicotinamide	Murine	Primary rat bone marrow cells	Protected against oxidative-stress-related cytotoxicity	[22]
	Vitamin B6	Pyridoxine and pyridoxal forms on PLA nanofibers	Monkey Canine Human	Cos-7, MDCK, and HEp-2 cells	Protected against oxidative stress	[23]
		Pyridoxal 5′-phosphate-immobilized TiO2 surfaces	Murine	MC3T3-E1	Improved cell proliferation, platelet aggregation and activation and blood coagulation	[24]
Inflammatory diseases	Folic acid or Folate	FA-conjugated chitosan for siRNA delivery	Murine	RAW 264.7	Enhanced cellular uptake and silencing effect of siRNAs	[25]
		Free folic acid	Human	THP-1	Folic acid pre-treatment diminished the inflammatory response in LPS-activated THP-1 macrophages	[26]
		FA/PEA/DNA/PECE composite hydrogel	Murine	C26 and 293T	Potential vector for gene delivery	[27]
		FA conjugated PEG-b-PAA@SPION	Murine	RAW 264.7	Promoted cellular uptake in activated macrophages	[28]
		Folate-targeted dendrimers	Murine	RAW 264.7	Promoted FR-mediated cellular uptake in activated macrophages	[29]
		Dexamethasone phosphate-loaded folate-conjugated polymeric nanoparticles	Murine	RAW 264.7	Promoted cellular uptake in activated macrophages and inhibits the production of pro-inflammatory cytokines and NO	[30]
		pH-responsive nanoparticles decorated with cell penetrating peptide and folate	Murine	RAW 264.7	Promoted FR-mediated cellular uptake in activated macrophages	[31]
	Nicotinamide	Free nicotinamide	Human	Primary monocytes	Reduced pro-inflammatory features of GM-MØ	[32]
Nervous System Repair	Folic acid	FA-loaded-CUPE nerve guidance conduits	Murine	Rat Schwann and PC-12 Adh cells	FA induced NT-3, NT-4/5 release and promoted proliferation and migration of both cell lines and differentiation of PC-12	[33]
		Free folic acid	Murine	Neonatal Sprague-Dawley NSCs	Promoted NSCs proliferation by a DNMT-and dose-dependent mechanism	[12]
			Murine	Neonatal Sprague-Dawley NSCs	Promoted NSCs proliferation by epigenetic regulation of PI3K/Akt/CREB pathway	[13]
			Murine	Neonatal Sprague-Dawley NSCs	Promoted neural and decreases astrocytic differentiation in NSCs by regulating DNMT	[14]
	Nicotinamide	Free nicotinamide	Murine	mESCs	Induced neuronal differentiation	[34]
	Cyanocobalamin (Vitamin B12)	B12-modified amphiphilic chitosan nanoparticles loaded with scutellarin	Human and zebra fish	Caco-2 cells and zebra fish	Showed good biocompatibility and high permeation in human cells	[35]
	Methylcobalamin (MeCbl)	MeCbl-loaded nanofibers	Murine	Primary cortical neurons	MeCbl promoted axonal outgrowth and the nanofibers released it gradually for up to 8 weeks	[36]
Dermal Repair	Folic acid	FA-modified HKUST-1	Human	HEKs, HDFs and HUVECs	FA reduced cytotoxicity while enhancing cell migration	[37]
	Pantothenic acid	Pantothenic acid/silk fibroin composite nanofibers	Murine	L929 cells	Especially promoted skin cells survival under oxidative stress conditions	[38]
	Alkyl-cobalamin (Vitamin B12)	B12-mediated photo-polymerized hydrogels	Human	HepG2 cells	Allowed cell survival	[39]
	Cyanocobalamin	B12-dependent photoresponsive protein hydrogels	Human	3T3 fibroblasts and human MSCs	Allowed facile release/recovery of the cells from 3D cultures without comprising their viability	[40]
Pancreatic Repair	Nicotinamide	Multiwalled carbon nanotubes functionalized with nicotinamide	Human	Hybrid beta-cell line (1.4E7)	Enhanced insulin production via MIF pathway	[41]
Cardiovascular System Repair	Folic acid	FA-derived hydrogel	Murine	Mouse iPSCs	1% wt hydrogels promoted cell proliferation and did not affect iPSCs differentiation towards cardiac lineage	[42]