title: Effect of cyclic tensile strain on proliferation of synovial cells seeded onto synthetic ligament scaffolds--an in vitro simulation.
abstract: OBJECTIVE
  Cyclic tensile strain is pivotal to the remodeling of tissue induced in implants used in reconstruction of anterior cruciate ligaments whether these implants were of autogenous tissues or synthetic materials. However, this process is poorly understood. The objective of this study was to investigate the short and medium-term effect of cyclic tensile strain on the proliferation of synovial cells seeded on ligament scaffolds.
  
  
  METHODS
  206 ligament scaffolds made from plasma treated polyester with an ultimate tensile strength of 320 N were used in this study. Synovial cells were obtained from the metatarsophalangeal joints of 2 years old bovines. After expansion of these, they were seeded onto the scaffolds which were subjected, in a specialized apparatus, to a cyclic tensile strain of 4.5% at a frequency of 1 Hz. Initially, the strain was applied for a period of 4 h, which was subsequently reduced in further experiments to 1.0 h and 0.5 h. In further tests, strains of approximately 2.5%, 1% and 0.6% were applied for 1 h at the same frequency. In all the above tests, which were short-term tests (lasting for approximately 1 day), cell proliferation was investigated by the uptake of thymidine with which cells were labeled according to prescribed protocols. Cell proliferation was further examined with light microscopy after 5 weeks and the degree of fill of inter-yarn spaces was quantified for strain amplitudes of 1, 2.5 and 4.5%. Equal number of control (not strained) specimens was used at each time point.
  
  
  RESULTS
  In the 1-day experiments, for all durations of application of cyclic strain (exercise), the effect of strain on cell proliferation was inhibitory during the period of exercise and up to 18 h from its commencement, but was stimulatory 22-24 h afterwards. This stimulatory effect was maximal at an exercise period of 1 h. The study has also shown that there is a threshold for the amplitude of the strain (1%), at and below which cell proliferation was not significantly different from that observed in control specimens (P was <0.05 for all data). After 5 weeks of cyclic strain application, it was shown that the higher the amplitude of strain the larger was the area occupied by cells of the intra-yarn space.
  
  
  CONCLUSIONS
  Both the amplitude of cyclic strain and duration of its application affect the proliferation of synovial cells seeded on ligament scaffolds. The data should be useful when selecting or designing an implant, and when prescribing a postoperative exercise regime.
authors.affiliation: Division of Bioengineering, Academic Unit of Musculoskeletal and Rehabilitation Medicine, Leeds School of Medicine, 36 Clarendon Road, LS2 9NZ Leeds, UK.
authors.forename: El Mostafa
authors.initials: el M
authors.lastname: Raïf
authors.forename: Bahaa B
authors.initials: BB
authors.lastname: Seedhom
mesh_terms: D000818:Animals; D002417:Cattle; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D049109:Cell Proliferation; D004247:DNA / Q000096:biosynthesis; D048091:Guided Tissue Regeneration / Q000295:instrumentation / Q000379:methods; D008022:Ligaments / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D011093:Polyethylene Terephthalates; D013582:Synovial Fluid / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D013718:Tensile Strength / Q000502:physiology
chemical_list: D011093:Polyethylene Terephthalates; D004247:DNA