title: Tissue engineering of flexor tendons: the effect of a tissue bioreactor on adipoderived stem cell-seeded and fibroblast-seeded tendon constructs.
abstract: OBJECTIVE
  Tissue-engineered flexor tendons could eventually be used for reconstruction of large tendon defects. The goal of this project was to examine the effect of a tissue bioreactor on the biomechanical properties of tendon constructs seeded with adipoderived stem cells (ASCs) and fibroblasts (Fs).
  
  
  METHODS
  Rabbit rear paw flexor tendons were acellularized and seeded with ASCs or Fs. A custom bioreactor applied a cyclic mechanical load of 1.25 N at 1 cycle/minute for 5 days onto the tendon constructs. Three additional groups were used as controls: fresh tendons and tendons reseeded with either ASCs or Fs that were not exposed to the bioreactor treatment and were left in stationary incubation for 5 days. We compared the ultimate tensile stress (UTS) and elastic modulus (EM) of bioreactor-treated tendons with the unloaded control tendons and fresh tendons. Comparison across groups was assessed using one-way analysis of variance with the significance level set at p<.05. Pairwise comparison between the samples was determined by using the Tukey test.
  
  
  RESULTS
  The UTS and EM values of bioreactor-treated tendons that were exposed to cyclic load were significantly higher than those of unloaded control tendons. Acellularized tendon constructs that were reseeded with ASCs and exposed to a cyclic load had a UTS of 66.76 MPa and an EM of 906.68 MPa; their unloaded equivalents had a UTS of 47.90 MPa and an EM of 715.57 MPa. Similar trends were found in the fibroblast-seeded tendon constructs that were exposed to the bioreactor treatment. The bioreactor-treated tendons approached the UTS and EM values of fresh tendons. Histologically, we found that cells reoriented themselves parallel to the direction of strain in response to cyclic strain.
  
  
  CONCLUSIONS
  The application of cyclic strain on seeded tendon constructs that were treated with the bioreactor helped achieve a UTS and an EM comparable with those of fresh tendons. Bioreactor pretreatment and alternative cell lines, such as ASCs and Fs, might therefore contribute to the in vitro production of strong tendon material.
authors.affiliation: Section of Plastic Surgery, Department of Veterans Affairs, and Division of Plastic Surgery, Stanford University Medical Center, Stanford, CA 94304, USA. ianangelidis@hotmail.com
authors.forename: Ioannis K
authors.initials: IK
authors.lastname: Angelidis
authors.forename: Johan
authors.initials: J
authors.lastname: Thorfinn
authors.forename: Ian D
authors.initials: ID
authors.lastname: Connolly
authors.forename: Derek
authors.initials: D
authors.lastname: Lindsey
authors.forename: Hung M
authors.initials: HM
authors.lastname: Pham
authors.forename: James
authors.initials: J
authors.lastname: Chang
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D019149:Bioreactors; D004195:Disease Models, Animal; D005121:Extremities; D005347:Fibroblasts / Q000166:cytology / Q000637:transplantation*; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D012680:Sensitivity and Specificity; D033581:Stem Cell Transplantation / Q000379:methods*; D013314:Stress, Mechanical; D013708:Tendon Injuries / Q000601:surgery; D013710:Tendons / Q000166:cytology / Q000637:transplantation*; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods*