title: *Thermosensitive Poly(N-vinylcaprolactam) Injectable Hydrogels for Cartilage Tissue Engineering.
abstract: Injectable hydrogels have gained prominence in the field of tissue engineering for minimally invasive delivery of cells for tissue repair and in the filling of irregular defects. However, many injectable hydrogels exhibit long gelation times or are not stable for long periods after injection. To address these concerns, we used thermosensitive poly(N-vinylcaprolactam) (PNVCL) hydrogels due to their cytocompatibility and fast response to temperature stimuli. Changes in the PNVCL molecular weight and concentration enabled the development of hydrogels with tunable mechanical properties and fast gelation times (<60 s when the temperature was raised from room temperature to physiologic temperature). Chondrocytes (CHs) and mesenchymal stem cells were encapsulated in PNVCL hydrogels and exhibited high viability (∼90%), as monitored by Live/Dead staining and Alamar Blue assays. Three-dimensional constructs of CH-laden PNVCL hydrogels supported cartilage-specific extracellular matrix production both in vitro and after subcutaneous injection in nude rats for up to 8 weeks. Moreover, biochemical analyses of constructs demonstrated a time-dependent increase in glycosaminoglycans (GAGs) and collagen, which were significantly augmented in the implants cultured in vivo. Histological analyses also demonstrated regular distribution of synthesized cartilage components, including abundant GAGs and type II collagen. The findings from this study demonstrate thermosensitive PNVCL as a candidate injectable biomaterial to deliver cells for cartilage tissue engineering.
authors.affiliation: 1 Interdisciplinary Laboratory of Electrochemistry and Ceramics, Department of Chemistry, Federal University of São Carlos , São Carlos, Brazil .|2 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Renata L
authors.initials: RL
authors.lastname: Sala
authors.affiliation: 2 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Mi Y
authors.initials: MY
authors.lastname: Kwon
authors.affiliation: 3 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.|4 Translational Musculoskeletal Research Center, CMC VA Medical Center , Philadelphia, Pennsylvania.
authors.forename: Minwook
authors.initials: M
authors.lastname: Kim
authors.affiliation: 3 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.|4 Translational Musculoskeletal Research Center, CMC VA Medical Center , Philadelphia, Pennsylvania.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gullbrand
authors.affiliation: 3 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.|4 Translational Musculoskeletal Research Center, CMC VA Medical Center , Philadelphia, Pennsylvania.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Henning
authors.affiliation: 2 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.|3 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.|4 Translational Musculoskeletal Research Center, CMC VA Medical Center , Philadelphia, Pennsylvania.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Mauck
authors.affiliation: 1 Interdisciplinary Laboratory of Electrochemistry and Ceramics, Department of Chemistry, Federal University of São Carlos , São Carlos, Brazil .
authors.forename: Emerson R
authors.initials: ER
authors.lastname: Camargo
authors.affiliation: 2 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Burdick
mesh_terms: D000818:Animals; D002209:Caprolactam / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002356:Cartilage / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D011923:Rats, Nude; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D020100:Hydrogels; D011108:Polymers; C086861:poly-N-vinylcaprolactam; D002209:Caprolactam
keywords: cartilage; hydrogels; injectable