Table 1. The use of hyaluronic acid in tissue engineering and its functional role in endogenous regeneration.

Model	Cell Type	Approach	Outcome Ref	Ref
		Tissue Engineering
in vivo (Rabbit)	Mesenchymal Progenitor Cells	Implantation of a HA-based three-D scaffold for cells in a full thickness osteochondral lesion	Cells adhered and proliferated on scaffold and lesions filled with this hydrogel, either seeded or unseeded with cells, achieved a faster and better healing.	[32]
in vivo (Rat)	Human Aortic Endothelial Cells (HAECs)	Implantation of a glycidyl methacrylate- HA (GMHA) scaffold into subcutaneous locations in rats to promote tissue repair	Implanted GMHA hydrogels showed good biocompatibility, little inflammatory response, i.e. suitable for modification with adhesive peptide sequences to use for wound healing applications.	[33]
in vitro, in vivo (Rat)	Human Mesenchymal Stem Cells (hMSC)	Implantation of an acrylated HA as a scaffold with BMP-2 and human mesenchymal stem cells (hMSCs) for rat calvarial defect regeneration	Viability in vitro was increased up to 55% in hydrogels with BMP-2; hydrogels with BMP-2 and MSCs had the highest expression of osteocalcin and bone formation with vascular markers for in vivo calvarial defects	[34]
in vitro	Ventral Mesencephalic Neural Progenitor Cells	Photoencapsulation of cells into HA hydrogels with varying numbers of photocrosslinkable methacrylate groups to investigate differentiation in 3D cultures that mimic geometry and mechanical properties of tissues	After three weeks, the majority of NPCs cultured in hydrogels with mechanical properties comparable to those of neonatal brain had differentiated into neurons, while NPCs cultured within stiffer hydrogels, with mechanical properties comparable to those of adult brain, had differentiated mostly into astrocytes.	[35]
in vitro, in vivo (Mouse)	Retinal Stem-Progenitor Cell (RSPC)	Development of HA and methylcellulose hydrogel for localized delivery to sub-retinal space	HAMC supported RSPC survival and proliferation in vitro and exhibiting ideal properties for delivery to the sub-retinal space for in vivo study.	[36]
in vivo (Rat & Rabbit)	Human Umbilical Cord Mesenchymal Stem Cells	Transplantation of hUCB-MSCs in 4% HA hydrogel composite into defect on the knee to confirm the regenerative potential in models	A composite of hUCB-MSCs with HA hydrogel to cartilage defects results in consistent cartilage regeneration and can be used for the regenerative treatment of full-thickness articular cartilage defects.	[37]
		Regeneration
in vivo (Newt)	Limb Blastema Cells	Investigation of changes in matrix in response to amputation and its role in blastema formation	HA is synthesized in the early-dedifferentiated blastema, is at highest level at 10 days of regeneration, and then degraded rapidly at 25 days of regeneration.	[38]
in vivo (Newt)	Limb Blastema Cells	Investigation of hyaluronidase activity and glycosaminoglycan synthesis in denervated (fail to regenerate) and innervated limbs	HA was the major GAG being produced, the ratio of HA to chondroitin sulfate was reduced in denervated limbs, and, hyaluronidase activity appears at the cartilage deposition stage, with or without a nerve.	[39]
in vivo (Newt))	Limb Blastema Cells	Investigation of the changes in the Matrix and Glycosaminoglycan synthesis during the initiation of regeneration	HA synthesis began at onset of tissue dedifferentiation, became maximal within 1 week, and continued throughout the period of active cell proliferation. Chondroitin sulfate synthesis began later, increased steadily, and reached high levels during chondrogenesis	[40]
in vivo (Newt)	Muscle satellite cells	Investigation of influence of the matrix on newt myoblasts in vitro	HA, tenascin-C and fibronectin influjence cell behaviors (DNA synthesis, migration, myotube fragmentation and myoblast fusion).	[41]