TY - JOUR
T1 - An advanced biphasic porous and injectable scaffold displays a fine balance between mechanical strength and remodeling capabilities essential for cartilage regeneration
AU - Zavala, Gabriela
AU - Viafara-García, Sergio M.
AU - Novoa, Javier
AU - Hidalgo, Carmen
AU - Contardo, Ingrid
AU - Díaz-Calderón, Paulo
AU - Alejandro González-Arriagada, Wilfredo
AU - Khoury, Maroun
AU - Acevedo, Juan Pablo
N1 - Publisher Copyright:
© 2023 The Royal Society of Chemistry.
PY - 2023/8/25
Y1 - 2023/8/25
N2 - An important challenge in tissue engineering is the regeneration of functional articular cartilage (AC). In the field, biomimetic hydrogels are being extensively studied as scaffolds that recapitulate microenvironmental features or as mechanical supports for transplanted cells. New advanced hydrogel formulations based on salmon methacrylate gelatin (sGelMA), a cold-adapted biomaterial, are presented in this work. The psychrophilic nature of this biomaterial provides rheological advantages allowing the fabrication of scaffolds with high concentrations of the biopolymer and high mechanical strength, suitable for formulating injectable hydrogels with high mechanical strength for cartilage regeneration. However, highly intricate cell-laden scaffolds derived from highly concentrated sGelMA solutions could be deleterious for cells and scaffold remodeling. On this account, the current study proposes the use of sGelMA supplemented with a mesophilic sacrificial porogenic component. The cytocompatibility of different sGelMA-based formulations is tested through the encapsulation of osteoarthritic chondrocytes (OACs) and stimulated to synthesize extracellular matrix (ECM) components in vitro and in vivo. The sGelMA-derived scaffolds reach high levels of stiffness, and the inclusion of porogens impacts positively the scaffold degradability and molecular diffusion, improved fitness of OACs, increased the expression of cartilage-related genes, increased glycosaminoglycan (GAG) synthesis, and improved remodeling toward cartilage-like tissues. Altogether, these data support the use of sGelMA solutions in combination with mammalian solid gelatin beads for highly injectable formulations for cartilage regeneration, strengthening the importance of the balance between mechanical properties and remodeling capabilities.
AB - An important challenge in tissue engineering is the regeneration of functional articular cartilage (AC). In the field, biomimetic hydrogels are being extensively studied as scaffolds that recapitulate microenvironmental features or as mechanical supports for transplanted cells. New advanced hydrogel formulations based on salmon methacrylate gelatin (sGelMA), a cold-adapted biomaterial, are presented in this work. The psychrophilic nature of this biomaterial provides rheological advantages allowing the fabrication of scaffolds with high concentrations of the biopolymer and high mechanical strength, suitable for formulating injectable hydrogels with high mechanical strength for cartilage regeneration. However, highly intricate cell-laden scaffolds derived from highly concentrated sGelMA solutions could be deleterious for cells and scaffold remodeling. On this account, the current study proposes the use of sGelMA supplemented with a mesophilic sacrificial porogenic component. The cytocompatibility of different sGelMA-based formulations is tested through the encapsulation of osteoarthritic chondrocytes (OACs) and stimulated to synthesize extracellular matrix (ECM) components in vitro and in vivo. The sGelMA-derived scaffolds reach high levels of stiffness, and the inclusion of porogens impacts positively the scaffold degradability and molecular diffusion, improved fitness of OACs, increased the expression of cartilage-related genes, increased glycosaminoglycan (GAG) synthesis, and improved remodeling toward cartilage-like tissues. Altogether, these data support the use of sGelMA solutions in combination with mammalian solid gelatin beads for highly injectable formulations for cartilage regeneration, strengthening the importance of the balance between mechanical properties and remodeling capabilities.
KW - Animals
KW - Biocompatible Materials
KW - Cartilage, Articular
KW - Chondrocytes/transplantation
KW - Gelatin
KW - Hydrogels
KW - Mammals
KW - Porosity
KW - Regeneration
KW - Tissue Engineering
KW - Tissue Scaffolds
UR - http://www.scopus.com/inward/record.url?scp=85170411080&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/87cc3943-5afa-365b-84e1-e835f706cbcb/
U2 - 10.1039/d3bm00703k
DO - 10.1039/d3bm00703k
M3 - Article
C2 - 37622217
AN - SCOPUS:85170411080
SN - 2047-4830
VL - 11
SP - 6801
EP - 6822
JO - Biomaterials Science
JF - Biomaterials Science
IS - 20
ER -