title: A method to screen and evaluate tissue adhesives for joint repair applications.
abstract: BACKGROUND
  Tissue adhesives are useful means for various medical procedures. Since varying requirements cause that a single adhesive cannot meet all needs, bond strength testing remains one of the key applications used to screen for new products and study the influence of experimental variables. This study was conducted to develop an easy to use method to screen and evaluate tissue adhesives for tissue engineering applications.
  
  
  METHODS
  Tissue grips were designed to facilitate the reproducible production of substrate tissue and adhesive strength measurements in universal testing machines. Porcine femoral condyles were used to generate osteochondral test tissue cylinders (substrates) of different shapes. Viability of substrates was tested using PI/FDA staining. Self-bonding properties were determined to examine reusability of substrates (n = 3). Serial measurements (n = 5) in different operation modes (OM) were performed to analyze the bonding strength of tissue adhesives in bone (OM-1) and cartilage tissue either in isolation (OM-2) or under specific requirements in joint repair such as filling cartilage defects with clinical applied fibrin/PLGA-cell-transplants (OM-3) or tissues (OM-4). The efficiency of the method was determined on the basis of adhesive properties of fibrin glue for different assembly times (30 s, 60 s). Seven randomly generated collagen formulations were analyzed to examine the potential of method to identify new tissue adhesives.
  
  
  RESULTS
  Viability analysis of test tissue cylinders revealed vital cells (>80%) in cartilage components even 48 h post preparation. Reuse (n = 10) of test substrate did not significantly change adhesive characteristics. Adhesive strength of fibrin varied in different test settings (OM-1: 7.1 kPa, OM-2: 2.6 kPa, OM-3: 32.7 kPa, OM-4: 30.1 kPa) and was increasing with assembly time on average (2.4-fold). The screening of the different collagen formulations revealed a substance with significant higher adhesive strength on cartilage (14.8 kPa) and bone tissue (11.8 kPa) compared to fibrin and also considerable adhesive properties when filling defects with cartilage tissue (23.2 kPa).
  
  
  CONCLUSIONS
  The method confirmed adhesive properties of fibrin and demonstrated the dependence of adhesive properties and applied settings. Furthermore the method was suitable to screen for potential adhesives and to identify a promising candidate for cartilage and bone applications. The method can offer simple, replicable and efficient evaluation of adhesive properties in ex vivo specimens and may be a useful supplement to existing methods in clinical relevant settings.
authors.affiliation: Tissue Engineering Laboratory and Berlin-Brandenburg Center for Regenerative Therapies, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Föhrer Strasse 15, Berlin 13353, Germany. tilo.dehne@charite.de
authors.forename: Tilo
authors.initials: T
authors.lastname: Dehne
authors.forename: Rolf
authors.initials: R
authors.lastname: Zehbe
authors.forename: Jan Philipp
authors.initials: JP
authors.lastname: Krüger
authors.forename: Aneliya
authors.initials: A
authors.lastname: Petrova
authors.forename: Rafael
authors.initials: R
authors.lastname: Valbuena
authors.forename: Michael
authors.initials: M
authors.lastname: Sittinger
authors.forename: Helmut
authors.initials: H
authors.lastname: Schubert
authors.forename: Jochen
authors.initials: J
authors.lastname: Ringe
mesh_terms: D000268:Adhesiveness; D000818:Animals; D002358:Cartilage, Articular / Q000601:surgery*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000637:transplantation*; D003094:Collagen / Q000737:chemistry; D017743:Equipment Reuse; D005269:Femur / Q000601:surgery*; D015718:Fibrin Tissue Adhesive / Q000737:chemistry; D007596:Joints / Q000601:surgery*; D019344:Lactic Acid / Q000737:chemistry; D008422:Materials Testing / Q000379:methods*; D023421:Models, Animal; D010027:Osteotomy; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013552:Swine; D013718:Tensile Strength; D013997:Time Factors; D014014:Tissue Adhesives / Q000737:chemistry*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014022:Tissue Survival
chemical_list: D015718:Fibrin Tissue Adhesive; D014014:Tissue Adhesives; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen