title: Articular cartilage generation applying PEG-LA-DM/PEGDM copolymer hydrogels.
abstract: Injuries to the human native cartilage tissue are particularly problematic because cartilage has little to no ability to heal or regenerate itself. Employing a tissue engineering strategy that combines suitable cell sources and biomimetic hydrogels could be a promising alternative to achieve cartilage regeneration. However, the weak mechanical properties may be the major drawback to use fully degradable hydrogels. Besides, most of the fully degradable hydrogels degrade too fast to permit enough extracellular matrix (ECM) production for neocartilage formation. In this study, we demonstrated the feasibility of neocartilage regeneration using swine articular chondrocytes photoencapsualted into poly (ethylene glycol) dimethacrylate (PEGDM) copolymer hydrogels composed of different degradation profiles: degradable (PEG-LA-DM) and nondegradable (PEGDM) macromers in molar ratios of 50/50, 60/40, 70/30, 80/20, and 90/10.
  
  
  
  Articular chondrocytes were isolated enzymatically from juvenile Yorkshire swine cartilage. 6 × 10(7) cells cells were added to each milliliter of macromer/photoinitiator (I2959) solution. Nonpolymerized gel containing the cells (100 μL) was placed in cylindrical molds (4.5 mm diameter × 6.5 mm in height). The macromer/photoinitiator/chondrocyte solutions were polymerized using ultraviolet (365 nm) light at 10 mW/cm(2) for 10 mins. Also, an articular cartilaginous ring model was used to examine the capacity of the engineered cartilage to integrate with native cartilage. Samples in the pilot study were collected at 6 weeks. Samples in the long-term experimental groups (60/40 and 70/30) were implanted into nude mice subcutaneously and harvested at 6, 12 and 18 weeks. Additionally, cylindrical constructs that were not implanted used as time zero controls. All of the harvested specimens were examined grossly and analyzed histologically and biochemically.
  
  
  
  Histologically, the neocartilage formed in the photochemically crosslinked gels resembled native articular cartilage with chondrocytes in lacunae and surrounded by new ECM. Increases in total DNA, glycosaminoglycan, and hydroxyproline were observed over the time periods studied. The neocartilage integrated with existing native cartilage.
  
  
  
  Articular cartilage generation was achieved using swine articular chondrocytes photoencapsulated in copolymer PEGDM hydrogels, and the neocartilage tissue had the ability to integrate with existing adjacent native cartilage.
authors.affiliation: Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.|Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, WACC 435, 15 Parkman Street, Boston, MA, 02114, USA.|Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Anestis
authors.initials: A
authors.lastname: Papadopoulos
authors.affiliation: Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ibusuki
authors.affiliation: Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.|Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, WACC 435, 15 Parkman Street, Boston, MA, 02114, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bichara
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.|MIRA Institute for Biotechnology and Technical Medicine, University Twente, Enschede, The Netherlands.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Saris
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Equine Science, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Malda
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO, USA.
authors.forename: Kristi S
authors.initials: KS
authors.lastname: Anseth
authors.affiliation: Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Gill
authors.affiliation: Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. MARANDOLPH@mgh.harvard.edu.|Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, WACC 435, 15 Parkman Street, Boston, MA, 02114, USA. MARANDOLPH@mgh.harvard.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Randolph
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000502:physiology*; D019902:Chondrocytes / Q000502:physiology*; D005240:Feasibility Studies; D005260:Female; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D019344:Lactic Acid; D010865:Pilot Projects; D061251:Primary Cell Culture; D012038:Regeneration; D013552:Swine
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D019344:Lactic Acid
keywords: Articular cartilage; Cartilage regeneration; PEG hydrogel; PEGDM hydrogel