title: Neovascularization Induced by the Hyaluronic Acid-Based Spongy-Like Hydrogels Degradation Products.
abstract: Neovascularization has been a major challenge in many tissue regeneration strategies. Hyaluronic acid (HA) of 3-25 disaccharides is known to be angiogenic due to its interaction with endothelial cell receptors. This effect has been explored with HA-based structures but a transitory response is observed due to HA burst biodegradation. Herein we developed gellan gum (GG)-HA spongy-like hydrogels from semi-interpenetrating network hydrogels with different HA amounts. Enzymatic degradation was more evident in the GG-HA with high HA amount due to their lower mechanical stability, also resulting from the degradation itself, which facilitated the access of the enzyme to the HA in the bulk. GG-HA spongy-like hydrogels hyaluronidase-mediated degradation lead to the release of HA oligosaccharides of different amounts and sizes in a HA content-dependent manner which promoted in vitro proliferation of human umbilical cord vein endothelial cells (HUVECs) but not their migration. Although no effect was observed in human dermal microvascular endothelial cells (hDMECs) in vitro, the implantation of GG-HA spongy-like hydrogels in an ischemic hind limb mice model promoted neovascularization in a material-dependent manner, consistent with the in vitro degradation profile. Overall, GG-HA spongy-like hydrogels with a sustained release of HA oligomers are valuable options to improve tissue vascularization, a critical issue in several applications in the tissue engineering and regenerative medicine field.
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine , AvePark - Parque da Ciência e Tecnologia, 4805-017 Barco, Taipas, Guimarães, Portugal.|ICVS/3B's - PT Government Associate Laboratory , Braga/Guimarães, Portugal.
authors.forename: Lucília P da
authors.initials: LP
authors.lastname: Silva
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine , AvePark - Parque da Ciência e Tecnologia, 4805-017 Barco, Taipas, Guimarães, Portugal.|ICVS/3B's - PT Government Associate Laboratory , Braga/Guimarães, Portugal.
authors.forename: Rogério P
authors.initials: RP
authors.lastname: Pirraco
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine , AvePark - Parque da Ciência e Tecnologia, 4805-017 Barco, Taipas, Guimarães, Portugal.|ICVS/3B's - PT Government Associate Laboratory , Braga/Guimarães, Portugal.
authors.forename: Tírcia C
authors.initials: TC
authors.lastname: Santos
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine , AvePark - Parque da Ciência e Tecnologia, 4805-017 Barco, Taipas, Guimarães, Portugal.|ICVS/3B's - PT Government Associate Laboratory , Braga/Guimarães, Portugal.
authors.forename: Ramon
authors.initials: R
authors.lastname: Novoa-Carballal
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine , AvePark - Parque da Ciência e Tecnologia, 4805-017 Barco, Taipas, Guimarães, Portugal.|ICVS/3B's - PT Government Associate Laboratory , Braga/Guimarães, Portugal.
authors.forename: Mariana T
authors.initials: MT
authors.lastname: Cerqueira
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine , AvePark - Parque da Ciência e Tecnologia, 4805-017 Barco, Taipas, Guimarães, Portugal.|ICVS/3B's - PT Government Associate Laboratory , Braga/Guimarães, Portugal.
authors.forename: Rui L
authors.initials: RL
authors.lastname: Reis
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine , AvePark - Parque da Ciência e Tecnologia, 4805-017 Barco, Taipas, Guimarães, Portugal.|ICVS/3B's - PT Government Associate Laboratory , Braga/Guimarães, Portugal.
authors.forename: Vitor M
authors.initials: VM
authors.lastname: Correlo
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine , AvePark - Parque da Ciência e Tecnologia, 4805-017 Barco, Taipas, Guimarães, Portugal.|ICVS/3B's - PT Government Associate Laboratory , Braga/Guimarães, Portugal.
authors.forename: Alexandra P
authors.initials: AP
authors.lastname: Marques
mesh_terms: D000818:Animals; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006820:Hyaluronic Acid; D020100:Hydrogels / Q000737:chemistry*; D051379:Mice; D018919:Neovascularization, Physiologic; D044968:Regenerative Medicine; D023822:Tissue Engineering
chemical_list: D020100:Hydrogels; D006820:Hyaluronic Acid
keywords: angiogenesis; biodegradation; gellan gum spongy-like hydrogels; hyaluronic acid; ischemia; neovascularization