title: Systematic Review of Biological Modulation of Healing in Anterior Cruciate Ligament Reconstruction.
abstract: BACKGROUND
  Whether biological modulation is effective to promote healing in anterior cruciate ligament (ACL) reconstruction remains unclear.
  
  
  OBJECTIVE
  To perform a systematic review of both clinical and experimental evidence of preclinical animal studies on biological modulation to promote healing in ACL reconstruction.
  
  
  METHODS
  Systematic review; Level of evidence, 2.
  
  
  METHODS
  A systematic search was performed using the PubMed, Ovid, and Scopus search engines. Inclusion criteria were clinical and animal studies involving subjects with ACL injury with the use of biological modulation to promote healing outcomes. Methodological quality of clinical studies was evaluated using the Critical Appraisal Skill Programme (CASP) appraisal tool, and animal studies were evaluated by a scoring system based on a published checklist of good animal studies.
  
  
  RESULTS
  Ten clinical studies and 50 animal studies were included. Twenty-five included studies were regarded as good quality, with a methodological score ≥5. These studies suggested that transforming growth factor-beta (TGF-β), mesenchymal stem cells, osteogenic factors, and modalities that reduce local inflammation may be beneficial to promote graft healing in ACL reconstruction.
  
  
  CONCLUSIONS
  This systematic review suggests that biological modulation is able to promote healing on top of surgical treatment for ACL injuries. This treatment strategy chiefly works through promotion of healing at the tunnel-graft interface, but the integrity of the intra-articular midsubstance of the graft would be another target for biological modulation.
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. ; Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Sai-Chuen
authors.initials: SC
authors.lastname: Fu
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. ; Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yau-Chuk
authors.initials: YC
authors.lastname: Cheuk
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. ; Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Shu-Hang
authors.initials: SH
authors.lastname: Yung
authors.affiliation: Department of Orthopaedic Surgery, Huddinge University Hospital, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christer Gustav
authors.initials: CG
authors.lastname: Rolf
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. ; Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Kai-Ming
authors.initials: KM
authors.lastname: Chan
keywords: anterior cruciate ligament; biological modulation; cell therapy; growth factor