title: Biomimetic fiber assembled gradient hydrogel to engineer glycosaminoglycan enriched and mineralized cartilage: An in vitro study.
abstract: The study investigated the potential of electrospun fiber assembled hydrogel, with physical gradients of chondroitin sulfate (CS) and sol-gel-derived bioactive glass (BG), to engineer hyaline and mineralized cartilage in a single 3D system. Electrospun poly(caprolactone) (PCL) fibers incorporated with 0.1% w/w of CS (CSL) and 0.5% w/w of CS (CSH), 2.4% w/w of BG (BGL) and 12.5% w/w of BG (BGH) were fabricated. The CS showed a sustained release up to 3 days from CSL and 14 days from CSH fibers. Chondrocytes secreted hyaline like matrix with higher sulfated glycosaminoglycans (sGAG), collagen type II and aggrecan on CSL and CSH fibers. Mineralization was observed on BGL and BGH fibers when incubated in simulated body fluid for 14 days. Chondrocytes cultured on these fibers secreted a mineralized matrix that consisted of sGAG, hypertrophic proteins, collagen type X, and osteocalcin. The CS and BG incorporated PCL fiber mats were assembled in an agarose-gelatin hydrogel to generate a 3D hybrid scaffold. The signals in the fibers diffused and generated continuous opposing gradients of CS (chondrogenic signal) and BG (mineralization) in the hydrogel. The chondrocytes were encapsulated in hybrid scaffolds; live dead assay at 48 h showed viable cells. Cells maintained their phenotype and secreted specific extracellular matrix (ECM) in response to signals within the hydrogel. Continuous opposing gradients of sGAG enriched and mineralized ECM were observed surrounding each cell clusters on gradient hydrogel after 14 days of culture in response to the physical gradients of raw materials CS and BG. A construct with gradient mineralization might accelerate integration to subchondral bone during in vivo regeneration.
authors.affiliation: Division of Tissue Engineering and Regeneration Technologies, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
authors.forename: Neethu
authors.initials: N
authors.lastname: Mohan
authors.affiliation: Division of Tissue Engineering and Regeneration Technologies, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
authors.forename: Jijo
authors.initials: J
authors.lastname: Wilson
authors.affiliation: Division of Tissue Engineering and Regeneration Technologies, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
authors.forename: Dexy
authors.initials: D
authors.lastname: Joseph
authors.affiliation: Division of Tissue Engineering and Regeneration Technologies, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
authors.forename: Dhanesh
authors.initials: D
authors.lastname: Vaikkath
authors.affiliation: Division of Tissue Engineering and Regeneration Technologies, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
authors.forename: Prabha D
authors.initials: PD
authors.lastname: Nair
mesh_terms: D000818:Animals; D032701:Biomimetics / Q000379:methods; D002356:Cartilage / Q000502:physiology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000008:administration & dosage / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006025:Glycosaminoglycans / Q000008:administration & dosage* / Q000378:metabolism; D006041:Goats; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D057139:Nanofibers / Q000737:chemistry / Q000648:ultrastructure; D011091:Polyesters / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D003692:Delayed-Action Preparations; D006025:Glycosaminoglycans; D011091:Polyesters; C016240:polycaprolactone; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D002809:Chondroitin Sulfates
keywords: gradients of signal; hyaline and mineralized cartilage; nanofiber-hydrogel hybrid system; signal encapsulated nanofibers