title: Tissue engineering of ligaments for reconstructive surgery.
abstract: OBJECTIVE
  The use of musculoskeletal bioengineering and regenerative medicine applications in orthopaedic surgery has continued to evolve. The aim of this systematic review was to address tissue-engineering strategies for knee ligament reconstruction.
  
  
  METHODS
  A systematic review of PubMed/Medline using the terms "knee AND ligament" AND "tissue engineering" OR "regenerative medicine" was performed. Two authors performed the search, independently assessed the studies for inclusion, and extracted the data for inclusion in the review. Both preclinical and clinical studies were reviewed, and the articles deemed most relevant were included in this article to provide relevant basic science and recent clinical translational knowledge concerning "tissue-engineering" strategies currently used in knee ligament reconstruction.
  
  
  RESULTS
  A total of 224 articles were reviewed in our initial PubMed search. Non-English-language studies were excluded. Clinical and preclinical studies were identified, and those with a focus on knee ligament tissue-engineering strategies including stem cell-based therapies, growth factor administration, hybrid biomaterial, and scaffold development, as well as mechanical stimulation modalities, were reviewed.
  
  
  CONCLUSIONS
  The body of knowledge surrounding tissue-engineering strategies for ligament reconstruction continues to expand. Presently, various tissue-engineering techniques have some potential advantages, including faster recovery, better ligamentization, and possibly, a reduction of recurrence. Preclinical research of these novel therapies continues to provide promising results. There remains a need for well-designed, high-powered comparative clinical studies to serve as a foundation for successful translation into the clinical setting going forward.
  
  
  METHODS
  Level IV, systematic review of Level IV studies.
authors.affiliation: Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.
authors.forename: MaCalus V
authors.initials: MV
authors.lastname: Hogan
authors.affiliation: Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Murawski
authors.affiliation: Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.. Electronic address: ffu@upmc.edu.
authors.forename: Freddie H
authors.initials: FH
authors.lastname: Fu
mesh_terms: D020341:Absorbable Implants; D001672:Biocompatible Materials; D002130:Calcium Phosphates; D016207:Cytokines / Q000627:therapeutic use; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000627:therapeutic use; D007719:Knee Joint / Q000601:surgery*; D008023:Ligaments, Articular / Q000601:surgery*; D045164:Mesenchymal Stem Cell Transplantation; D019637:Orthopedic Procedures / Q000379:methods; D053657:Platelet-Rich Plasma; D019736:Prostheses and Implants; D044968:Regenerative Medicine; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; C020243:calcium phosphate