title: Self-crosslinked oxidized alginate/gelatin hydrogel as injectable, adhesive biomimetic scaffolds for cartilage regeneration.
abstract: Biopolymeric hydrogels that mimic the properties of extracellular matrix have great potential in promoting cellular migration and proliferation for tissue regeneration. The authors reported earlier that rapidly gelling, biodegradable, injectable hydrogels can be prepared by self-crosslinking of periodate oxidized alginate and gelatin in the presence of borax, without using any toxic crosslinking agents. The present paper investigates the suitability of this hydrogel as a minimally invasive injectable, cell-attractive and adhesive scaffold for cartilage tissue engineering for the treatment of osteoarthritis. Time and frequency sweep rheology analysis confirmed gel formation within 20s. The hydrogel integrated well with the cartilage tissue, with a burst pressure of 70±3mmHg, indicating its adhesive nature. Hydrogel induced negligible inflammatory and oxidative stress responses, a prerequisite for the management and treatment of osteoarthritis. Scanning electron microscopy images of primary murine chondrocytes encapsulated within the matrix revealed attachment of cells onto the hydrogel matrix. Chondrocytes demonstrated viability, proliferation and migration within the matrix, while maintaining their phenotype, as seen by expression of collagen type II and aggrecan, and functionality, as seen by enhanced glycosoaminoglycan (GAG) deposition with time. DNA content and GAG deposition of chondrocytes within the matrix can be tuned by incorporation of bioactive signaling molecules such as dexamethasone, chondroitin sulphate, platelet derived growth factor (PDGF-BB) and combination of these three agents. The results suggest that self-crosslinked oxidized alginate/gelatin hydrogel may be a promising injectable, cell-attracting adhesive matrix for neo-cartilage formation in the management and treatment of osteoarthritis.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
authors.forename: Biji
authors.initials: B
authors.lastname: Balakrishnan
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Joshi
authors.affiliation: Biomaterials Science and Technology, Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036, India.
authors.forename: Athipettah
authors.initials: A
authors.lastname: Jayakrishnan
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India. Electronic address: rinti@iitb.ac.in.
authors.forename: Rinti
authors.initials: R
authors.lastname: Banerjee
mesh_terms: D000268:Adhesiveness; D000464:Alginates / Q000737:chemistry; D000818:Animals; D040761:Biomimetic Materials / Q000008:administration & dosage*; D002448:Cell Adhesion / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D003432:Cross-Linking Reagents / Q000737:chemistry; D019544:Equipment Failure Analysis; D005780:Gelatin / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D051457:Hyaline Cartilage / Q000166:cytology* / Q000254:growth & development*; D020100:Hydrogels / Q000737:chemistry; D007267:Injections; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D011474:Prosthesis Design; D012038:Regeneration / Q000502:physiology*; D014014:Tissue Adhesives / Q000008:administration & dosage; D023822:Tissue Engineering / Q000295:instrumentation; D054457:Tissue Scaffolds
chemical_list: D000464:Alginates; D003432:Cross-Linking Reagents; D006603:Hexuronic Acids; D020100:Hydrogels; D014014:Tissue Adhesives; D020723:Glucuronic Acid; D005780:Gelatin
keywords: Alginate; Cartilage; Hydrogels; Injectable; Tissue engineering