title: Development of biodegradable hyper-branched tissue adhesives for the repair of meniscus tears.
abstract: Meniscus tears are one of the most commonly occurring injuries of the knee joint. Current meniscus repair techniques are challenging and do not bring fully satisfactory results. Tissue adhesives are a promising alternative, since they are easy to apply and cause minimal tissue trauma. In this study, a series of amphiphilic copolymers based on polyethylene glycol, trimethylene carbonate and citric acid were synthesized and subsequently end-functionalized with hexamethylene diisocyanate to form reactive adhesive materials. The shear adhesive strength of the networks to bovine meniscus tissue measured in a lap-shear adhesion test ranged between 20 and 80 kPa, which was better than for fibrin glue (10 kPa). The elastic modulus of the networks depended on composition and was in the same range as that of human meniscus. Cell compatibility was assessed using Alamar Blue staining after incubation of the bovine meniscus cells with different concentrations of the glues for 7 days. Cell viability was not affected after adding up to 3mg of the adhesive/mL of medium. The proposed materials are suitable candidates to be used as resorbable tissue adhesives for meniscus repair. They have excellent mechanical and adhesive properties that can be adjusted by varying the composition of the copolymers.
  
  
  CONCLUSIONS
  Meniscal tears often occur and current treatment strategies do not bring fully satisfactory results. Use of biodegradable tissue adhesives would be an interesting option, but currently available adhesives are not suited due to toxicity or poor mechanical properties. Here, we describe the development of novel biodegradable, hyper-branched, adhesive copolymers. These adhesives cure upon contact with water forming flexible networks. Their adhesion to bovine meniscus tissue was significantly better than that of clinically used fibrin glue. The tensile properties of the cured networks were in the same range of values of the human meniscus. When physiologically relevant amounts were added to cells in culture, not toxic effects were observed. Therefore, the proposed materials are interesting resorbable tissue adhesives for meniscus repair.
authors.affiliation: Department of Biomaterials Science and Technology, MIRA Institute, University of Twente, Enschede, The Netherlands; Orthopaedic Research Laboratory, Department of Orthopaedics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: A I
authors.initials: AI
authors.lastname: Bochyńska
authors.affiliation: Orthopaedic Research Laboratory, Department of Orthopaedics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: T G
authors.initials: TG
authors.lastname: Van Tienen
authors.affiliation: Orthopaedic Research Laboratory, Department of Orthopaedics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Hannink
authors.affiliation: Orthopaedic Research Laboratory, Department of Orthopaedics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Buma
authors.affiliation: Department of Biomaterials Science and Technology, MIRA Institute, University of Twente, Enschede, The Netherlands; University Medical Centre Groningen, University of Groningen, W.J. Kolff Institute, Department of Biomedical Engineering, Groningen, The Netherlands. Electronic address: d.w.grijpma@utwente.nl.
authors.forename: D W
authors.initials: DW
authors.lastname: Grijpma
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D017953:Isocyanates / Q000737:chemistry; D008422:Materials Testing / Q000379:methods*; D008592:Menisci, Tibial / Q000187:drug effects / Q000473:pathology*; D011092:Polyethylene Glycols / Q000737:chemistry; D011140:Polyurethanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012421:Rupture; D014014:Tissue Adhesives / Q000494:pharmacology*; D014867:Water / Q000737:chemistry; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D001672:Biocompatible Materials; D017953:Isocyanates; D011140:Polyurethanes; D014014:Tissue Adhesives; D014867:Water; D011092:Polyethylene Glycols
keywords: Biodegradable; Blockcopolymer; Hyper-branched; Isocyanate; Meniscus; Polyurethane; Tissue adhesive