title: A Novel Silk Fiber-Based Scaffold for Regeneration of the Anterior Cruciate Ligament: Histological Results From a Study in Sheep.
abstract: Because of ongoing problems with anterior cruciate ligament (ACL) reconstruction, new approaches in the treatment of ACL injuries, particularly strategies based on tissue engineering, have gained increasing research interest. To allow for ACL regeneration, a structured scaffold that provides a mechanical basis, has cells from different sources, and comprises mechanical as well as biological factors is needed. Biological materials, biodegradable polymers, and composite materials are being used and tested as scaffolds. The optimal scaffold for ACL regeneration should be biocompatible and biodegradable to allow tissue ingrowth but also needs to have the right mechanical properties to provide immediate mechanical stability.
  
  
  
  The study hypotheses were that (1) a novel degradable silk fiber-based scaffold with mechanical properties similar to the native ACL will be able to initiate ligament regeneration after ACL resection and reconstruction under in vivo conditions and (2) additional cell seeding of the scaffold with autologous stromal vascular fraction-containing adipose-derived stem cells will increase regenerative activity.
  
  
  
  Controlled laboratory study.
  
  
  
  A total of 33 mountain sheep underwent ACL resection and randomization to 2 experimental groups: (1) ACL reconstruction with a scaffold alone and (2) ACL reconstruction with a cell-seeded scaffold. Histological evaluation of the intra-articular portion of the reconstructed/regenerated ligament was performed after 6 and 12 months.
  
  
  
  After 6 months, connective tissue surrounded the silk scaffold with ingrowth in some areas. The cell-seeded scaffolds had a significant lower silk content compared with the unseeded scaffolds and demonstrated a higher content of newly formed tissue. After 12 months, the density of the silk fibers decreased significantly, and the ingrowth of newly formed tissue increased in both groups. No differences between the 2 groups regarding silk fiber degradation and regenerated tissue were detected at 12 months.
  
  
  
  The novel silk fiber-based scaffold was able to stimulate ACL regeneration under in vivo conditions. Additional cell seeding led to increased tissue regeneration and decreased silk fiber content at 6 months, whereas these differences were not present at 12 months.
  
  
  
  ACL regeneration using a silk fiber-based scaffold with and without additional cell seeding may provide a new treatment option after joint injuries.
authors.affiliation: Department of Biochemical Engineering, University of Applied Sciences Technikum Wien, Vienna, Austria Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Vienna, Austria Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Teuschl
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Vienna, Austria Karl Donath Laboratory for Hard Tissue and Biomaterial Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Patrick
authors.initials: P
authors.lastname: Heimel
authors.affiliation: Austrian Cluster for Tissue Regeneration, Vienna, Austria Department of Traumatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nürnberger
authors.affiliation: Department of Experimental Trauma Surgery, Technical University of Munich, Munich, Germany.
authors.forename: Martijn
authors.initials: M
authors.lastname: van Griensven
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Vienna, Austria Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Vienna, Austria Austrian Cluster for Tissue Regeneration, Vienna, Austria thnau@hotmail.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nau
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000502:physiology*; D059549:Anterior Cruciate Ligament Reconstruction; D005260:Female; D012038:Regeneration; D012756:Sheep; D047011:Silk; D054457:Tissue Scaffolds
chemical_list: D047011:Silk
keywords: anterior cruciate ligament; autologous stem cells; stromal vascular fraction; tissue engineering