Table 1.

Summary of cross-linking methods used to integrate liposomes to scaffolds for bone regeneration.

Drug	Liposome Composition	Scaffold	Cross-Linking Method	Notes	Reference
Plasmid DNA encoding RUNX2	DODAP, HSPC, Cholesterol, and DSPE-PEG or DSPE-PEG-Mal	Polycaprolactone nanofiber meshes	Thioether linkage of maleimide and thiol group	Osteogenic activities in human bone-marrow mesenchymal stem cells in vitro	[40]
Dexamethasone	DODAP, HSPC, Cholesterol, and DSPE-PEG or DSPE-PEG-Mal	Polycaprolactone nanofiber meshes	Thioether linkage of maleimide and thiol group	Osteogenic activities in human bone-marrow mesenchymal stem cells in vitro	[44]
Noggin siRNA	Stearylamine and cholesterol	Methacrylated glycol chitosan hydrogel	Encapsulation	Osteogenic and bone regeneration activities in vitro and in vivo	[41]
Phenamil and Noggin siRNA	Stearylamine and cholesterol	Methacrylated glycol chitosan hydrogel	Encapsulation	Osteogenic and bone regeneration activities in vitro and in vivo	[42]
20(s)-hydroxycholesterol and Plasmid DNA encoding sonic hedgehog	Palmitic acid and 20(s)-hydroxycholesterol	Porous hydroxyapatite-coated PLGA scaffold	Electrostatic interaction of alendronate and apatite	Osteogenic and bone regeneration activities in vitro and in vivo	[22]
Kartogenin	Lecithin and cholesterol	Gelatin methacryloyl hydrogel	Encapsulation via the physical network hindrance and non-covalent interaction	Extended joint retention, in vitro chondrogenic activities, and therapeutic effects in osteoarthritis model in vivo	[37]
Dexamethasone	(N-{6-amino-1-[N-(9Z) -octadec9-enylamino] -1-oxohexan-(2S) -2- yl} –N’- {2- [N, N-bis(2-aminoethyl) amino] ethyl} -2-hexadecylpropandiamide) (OO4) and DOPE	Glass coverslips, gold sensors, and silicon substrates	Layer-by-Layer coating with polyethyleneimine, collagen type I, chondroitin sulfate, and liposome	Enhanced adhesion and osteogenic differentiation of C2C12 myoblasts in vitro	[43]
Salvianic acid A	Lecithin, cholesterol, and cholesterol-pyrophosphate	Collagen sponge	Absorption	Improved bone healing via the regulation of HDAC3-mediated endochondral ossification in rabbit segmental defect model	[23]
Deferoxamine and BMP-2	Phosphatidylcholin and Chol	Gelatin methacryloyl hydrogel	Hydrogen bond and hydrogel network micro-cross-linking	Enhanced mechanical property by liposome encapsulation, controlled phase release of various type of drugs, osteogenesis, angiogenesis, mature lamella bone formation in vivo	[38]
Deferoxamine	Lecithin and cholesterol	Gelatin methacryloyl hydrogel and 3D printed bioceramic scaffold	Encapsulation	Designed biomimetic ‘lotus’ biological structure, increased the expression of vascularization, and pro-osteogenic effects in vitro/in vivo	[39]
Curcumin	1,2-dimyristoylsn-glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (sodium salt) (DMPG)	3D printed calcium phosphate scaffolds	Absorption and ionic interaction	Cytotoxic against in vitro osteosarcoma (bone cancer) cells and promoted osteoblast (healthy bone cell) cell growth	[34]
20(s)-hydroxycholesterol	Stearylamine and 20(s)-hydroxycholesterol	Methacrylated glycol chitosan hydrogel	Encapsulation	Designed non-phospholipid liposome, named sterosome, which has intrinsic osteoinductivity, and enhanced osteogenic activities in vitro and bone formation in vivo via hedgehog signaling	[27]
20(s)-hydroxycholesterol and purmorphamine	Stearylamine and 20(s)-hydroxycholesterol	Porous PLGA scaffold	Polydopamine-mediated layer-by-layer coating (Schiff base formation and Michael-type addition)	Osteogenic activities in vitro and bone formation in vivo via hedgehog signaling	[29]
20(s)-hydroxycholesterol and smoothened agonist (SAG)	Stearylamine and 20(s)-hydroxycholesterol	Porous hydroxyapatite-coated PLGA scaffold	Polydopamine-mediated layer-by-layer coating (Schiff base formation and Michael-type addition)	Osteogenic activities in vitro and bone formation in vivo via hedgehog signaling	[30]
Aspirin and bone forming peptide-1	DSPE-PEG-NH2, 1,2- dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and cholesterol	3D printed polycaprolactone scaffold	Polydopamine-mediated coating	Osteogenic activities in vitro and bone formation in vivo via PI3K/AKT signaling	[36]
Aspirin	DSPE-PEG-NH2, DPPC, and cholesterol	3D printed polycaprolactone scaffold	Polydopamine-mediated coating	Osteogenic activities in vitro and ectopic bone formation in vivo	[35]
BMP-2 peptide	HSPC or DPPC, Cholesterol, and mPEG-DSPE-maleimide	Electrospun poly L-lactic acid nanofibers	Thioether linkage of maleimide and thiol group	Sustained release of BMP-2 peptide up to 21 days, enhanced in vitro osteogenic activities, and initiated ectopic bone formation	[33]
107–111 pentapeptide of the parathyroid hormone-related protein (PTHrP 107-111)	MSPC, DSPE-PEG-maleimide, and DPPC	Collagen-hydroxyapatite scaffolds	Thioether linkage of maleimide and thiol group	Triggered release of PTHrP 107-111 by thermal stimulation and enhanced pro-osteogenic activities in vitro	[18]
N′-Dodecanoylisonicotinohydrazide	Phospholipid	PLGA-PEG-PLGA hydrogel	Encapsulation	Developed a liposome-in-hydrogel and sustained drug release	[19]
Carboxyfluorescein, doxorubicin, and lysozyme; not for bone tissue engineering	DSPC, cholesterol, and DSPE-PEG or DSPE-PEG-thiol bisphosphonate	Collagen-hydroxyapatite scaffolds	Electrostatic interaction of bisphosphonate and apatite	Increased affinity to the scaffold and sustained drug release	[21]
BMP-2	Lecithin, cholesterol, and octadecylamine	PEG and Ag ion hydrogel	Encapsulation	Promoted osteogenic differentiation in vitro and local bone remodeling of osteoporotic fracture in vivo because of increased localization efficacy at injected site	[20]
CKIP-1 siRNA	DOTAP, DOPE, cholesterol, DSPE-mPEG2000, and DSPE-PEG2000-maleimide	Bovine bone scaffold	Electrostatic interaction	Osteogenic activities in vitro and bone repair in vivo via CKIP-1 knock down	[25]