title: Characteristics of repair tissue in second-look and third-look biopsies from patients treated with engineered cartilage: relationship to symptomatology and time after implantation.
abstract: BACKGROUND
  The present study established characteristics of tissue regrowth in patients suffering knee lesions treated with grafts of autologous chondrocytes grown on three-dimensional hyaluronic acid biomaterials.
  
  
  METHODS
  This multicentred study involved a second-look arthroscopy/biopsy, 5 to 33 months post implant (n = 63). Seven patients allowed a third-look biopsy, three of which were performed 18 months post implant. Characteristics of tissues were histologically and histochemically evaluated. The remaining bone stubs were evaluated for cartilage/bone integration. For data analysis, biopsies were further divided into those obtained from postoperative symptomatic patients (n = 41) or from asymptomatic patients (n = 22).
  
  
  RESULTS
  The percentage of hyaline regenerated tissues was significantly greater in biopsies obtained after, versus within, 18 months of implantation. Differences were also observed between symptomatic and asymptomatic patients: reparative tissues taken from symptomatic patients 18 months after grafting were mainly fibrocartilage or mixed (hyaline-fibrocartilage) tissue, while tissues taken from asymptomatic patients were hyaline cartilage in 83% of biopsies. In a small group of asymptomatic patients (n = 3), second-look and third-look biopsies taken 18 months after surgery confirmed maturation of the newly formed tissue over time. Cartilage maturation occurred from the inner regions of the graft, in contact with subchondral bone, towards the periphery of the implant.
  
  
  CONCLUSIONS
  The study indicates that, in asymptomatic patients after chondrocyte implantation, regenerated tissue undergoes a process of maturation that in the majority of cases takes longer than 18 months for completion and leads to hyaline tissue and not fibrous cartilage. Persistence of symptoms might reflect the presence of a nonhyaline cartilage repair tissue.
authors.affiliation: Department of Histology, Microbiology and Medical Biotechnology, Histology Unit, Faculty of Medicine, University of Padova, Padova, Italy. paola.brun@unipd.it
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.forename: Sally C
authors.initials: SC
authors.lastname: Dickinson
authors.forename: Barbara
authors.initials: B
authors.lastname: Zavan
authors.forename: Roberta
authors.initials: R
authors.lastname: Cortivo
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Hollander
authors.forename: Giovanni
authors.initials: G
authors.lastname: Abatangelo
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002358:Cartilage, Articular / Q000737:chemistry / Q000637:transplantation*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007719:Knee Joint / Q000737:chemistry / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D024162:Second-Look Surgery / Q000379:methods*; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D016378:Tissue Transplantation / Q000379:methods; D014945:Wound Healing / Q000502:physiology*; D055815:Young Adult