title: Ligament regeneration using an absorbable stent-shaped poly-L-lactic acid scaffold in a rabbit model.
abstract: OBJECTIVE
  Ligaments are frequently damaged in sports activities and trauma, and severe ligament injury can lead to joint instability and osteoarthritis. In this study, we aimed to regenerate the medial collateral ligament (MCL) using an absorbable stent-shaped poly-L-lactic acid (PLLA) scaffold in a rabbit model to examine the biocompatibility and mechanical properties.
  
  
  METHODS
  Twenty-three Japanese white rabbits were used in this study. MCL defects were surgically created in the knee joints and then reconstructed using stent-shaped PLLA scaffolds. As controls, flexor digitorum longus (FDL) tendons were implanted into the contralateral knees. Seven rabbits were sacrificed at three time points, conducted four, eight and 16 weeks after the operation. The regenerated tissues were histologically evaluated using fibre alignment scoring, morphology of fibroblast scoring and immunohistochemical analysis of types I and III collagen. The regenerated tissues were also biomechanically evaluated by measuring the ultimate failure load and stiffness.
  
  
  RESULTS
  At four weeks post-operation, spindle-shaped cells were observed on the inside of the scaffolds. At eight weeks, maturation of the regenerated tissues and collagen fibre alignment parallel to the ligaments was observed. At 16 weeks, the fibre alignment had become denser. The fibre alignment and morphology of fibroblast scores significantly increased in a time-dependent manner. Expression of type I collagen was more strongly observed in the scaffold group at eight and 16 weeks post-operation than at four weeks. Type III collagen was also observed at four, eight and 16 weeks post-operation. A thin layer of fibrocartilage was observed at the ligament-bone junction at eight and 16 weeks. The ultimate failure load of the scaffold group was 46.7 ± 20.7 N, 66.5 ± 11.0 N and 74.3 ± 11.5 N at four, eight and 16 weeks post-operation, respectively. There was no statistical difference between the normal MCL and the scaffold group at 16 weeks post-operation.
  
  
  CONCLUSIONS
  The stent-shaped PLLA scaffold allowed for MCL regeneration with type I collagen expression and fibrocartilage formation and resulted in sufficient mechanical function.
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Hanako
authors.initials: H
authors.lastname: Nishimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kokubu
authors.forename: Atsuyuki
authors.initials: A
authors.lastname: Inui
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mifune
authors.forename: Kotaro
authors.initials: K
authors.lastname: Nishida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujioka
authors.forename: Kumiko
authors.initials: K
authors.lastname: Yokota
authors.forename: Chiaki
authors.initials: C
authors.lastname: Hiwa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001696:Biomechanical Phenomena; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D004548:Elasticity; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D051445:Fibrocartilage / Q000378:metabolism / Q000473:pathology; D048091:Guided Tissue Regeneration; D020007:Implants, Experimental; D007718:Knee Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D019344:Lactic Acid; D017888:Medial Collateral Ligament, Knee / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D011091:Polyesters; D011108:Polymers; D011475:Prosthesis Failure; D011817:Rabbits; D015607:Stents; D013264:Stifle / Q000293:injuries* / Q000473:pathology; D013710:Tendons / Q000637:transplantation; D054457:Tissue Scaffolds; D016896:Treatment Outcome; D014945:Wound Healing / Q000502:physiology*
chemical_list: D001672:Biocompatible Materials; D024042:Collagen Type I; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)