title: Engineering 3D-Bioplotted scaffolds to induce aligned extracellular matrix deposition for musculoskeletal soft tissue replacement.
abstract: OBJECTIVE
  Tissue engineering and regenerative medicine approaches have the potential to overcome the challenges associated with current treatment strategies for meniscus injuries. 3D-Bioplotted scaffolds are promising, but have not demonstrated the ability to guide the formation of aligned collagenous matrix in vivo, which is critical for generating functional meniscus tissue. In this study, we evaluate the ability of 3D-Bioplotted scaffold designs with varying interstrand spacing to induce the deposition of aligned matrix in vivo.
  
  
  METHODS
  3D-Bioplotted polycaprolactone scaffolds with 100, 200, or 400 μm interstrand spacing were implanted subcutaneously in a rat model for 4, 8, or 12 weeks. Scaffolds were harvested, paraffin-embedded, sectioned, and stained to visualize cell nuclei and collagen. Quantitative image analysis was used to evaluate cell density, matrix fill, and collagen fiber alignment within the scaffolds.
  
  
  RESULTS
  By 4 weeks, cells had infiltrated the innermost scaffold regions. Similarly, collagenous matrix filled interstrand regions nearly completely by 4 weeks. By 12 weeks, aligned collagen was present in all scaffolds. Generally, alignment along the scaffold strands increased over time for all three interstrand spacing groups. Distribution of collagen fiber alignment angles narrowed as interstrand spacing decreased.
  
  
  CONCLUSIONS
  3D-Bioplotted scaffolds allow for complete cell infiltration and collagenous matrix production throughout the scaffold. The ability to use interstrand spacing as a means of controlling the formation of aligned collagen in vivo was demonstrated, which helps establish a design space for scaffold-based meniscus tissue engineering.
authors.affiliation: a Department of Biomedical Engineering , North Carolina State University , Raleigh , NC , USA and University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|b Comparative Medicine Institute , North Carolina State University , Raleigh , NC , USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Warren
authors.affiliation: b Comparative Medicine Institute , North Carolina State University , Raleigh , NC , USA.|c Fitts Department of Industrial and Systems Engineering , North Carolina State University , Raleigh , NC , USA.|d Center for Additive Manufacturing and Logistics , North Carolina State University , Raleigh , NC , USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Huebner
authors.affiliation: e Department of Orthopedics , University of North Carolina School of Medicine , Chapel Hill , NC , USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Spang
authors.affiliation: a Department of Biomedical Engineering , North Carolina State University , Raleigh , NC , USA and University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|b Comparative Medicine Institute , North Carolina State University , Raleigh , NC , USA.|c Fitts Department of Industrial and Systems Engineering , North Carolina State University , Raleigh , NC , USA.|d Center for Additive Manufacturing and Logistics , North Carolina State University , Raleigh , NC , USA.
authors.forename: Rohan A
authors.initials: RA
authors.lastname: Shirwaiker
authors.affiliation: a Department of Biomedical Engineering , North Carolina State University , Raleigh , NC , USA and University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|b Comparative Medicine Institute , North Carolina State University , Raleigh , NC , USA.|e Department of Orthopedics , University of North Carolina School of Medicine , Chapel Hill , NC , USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Fisher
mesh_terms: D000818:Animals; D002452:Cell Count; D048430:Cell Shape; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D021621:Imaging, Three-Dimensional; D008297:Male; D009142:Musculoskeletal Physiological Phenomena; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology*; D034421:Sus scrofa; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D003094:Collagen
keywords: 3D printing; Biofabrication; meniscus; scaffold; tissue engineering