Advances in polymer-based hydrogel systems for adipose-derived mesenchymal stem cells toward bone regeneration

Table 1 Hydrogel systems and their efficacy, guiding future scaffold design in bone tissue engineering

Scaffold compositions	Fabrication methods	In vitro models	In vivo models	Inferences	Ref.
Chondroitin-6-sulfate (CHA)/glycol CS (GCS)/maleic anhydride-modified polyethylene glycol (DF-PEG) (CHA/SF/GCS/DF-PEG) hydrogels	Freeze drying	BM-MSCs, human embryonic kidney cells (HEK293), mouse osteoblastic progenitor cells, mouse macrophages (RAW264.7)	Adult mouse fracture model (BALB/c)	Hydrogel with BM-MSC-exo regulated macrophage polarization and angiogenesis to enhance bone regeneration	[63]
Methacrylate-silk fibroin/nano-HAp hydrogels	Photo-crosslinking	RAW 264.7 cells, BM-MSCs	Rat femoral defect	Elevated osteochondral repair by macrophage M2 polarization has been reported	[64]
Ultrasound-triggered ultrashort peptide SESSE nanofiber hydrogels	Ionic gelation method	BM-MSCs	C57BL/6J mouse bone defect model	Increased M2 polarization led to secretion of BMP-2 and IGF-I, and enhanced bone regeneration	[65]
Alpha-tricalcium phosphate/COL bioceramic ink/sanitizer-based hydrogels	3D-bioceramic printing	MC3T3 cells	-	Improved mechanical properties, increased cellular growth and osteogenic activity have been reported	[66]
Nano-HAp/GEL methacrylate/oxidized sodium ALG hydrogels loaded with BMP7	Photo-crosslinking	Rat BM-MSCs	Rat distal femur defect model	Enhanced osteogenic differentiation and bone formation have been reported	[67]
GEL-Bletilla striata polysaccharide-mesoporous bioactive glass hydrogels	Schiff base reaction and hydrogen bonding	Bone marrow-derived macrophages	Rat cranial defect model	Enhanced immunomodulation and bone regeneration were reported	[68]
Poly (L-glutamic acid) (PLG) grafted with tyramine (PLG-g-TA) polymer, VEGF, and strontium-doped borosilicate bioactive glass nanoparticles	Enzyme cross-linking	Rat BM-MSCs, human umbilical vein endothelial cells, and Raw264.7 cells	Rat cranial bone defects	Enhanced vascularization, osteogenesis, and angiogenesis have been reported	[69]
Amino-functionalized barium titanate nanoparticle hydrogels	Schiff base reaction and hydrogen bonding	BM-MSCs	Rat calvarial defect model	Enhanced ALP, BMP2, OPN, OCN, and COL-I expression and new bone formation have been reported	[70]

ALG: Alginate; BM-MSC: Bone marrow-derived mesenchymal stem cell; CS: Chitosan; GEL: Gelatin; Hap: Hydroxyapatite; VEGF: Vascular endothelial growth factor; 3D: Three-dimensional.