title: Aligned multilayered electrospun scaffolds for rotator cuff tendon tissue engineering.
abstract: The rotator cuff consists of several tendons and muscles that provide stability and force transmission in the shoulder joint. Whereas most rotator cuff tears are amenable to suture repair, the overall success rate of repair is low, and massive tears are prone to re-tear. Extracellular matrix (ECM) patches are used to augment suture repair, but they have limitations. Tissue-engineered approaches provide a promising solution for massive rotator cuff tears. Previous studies have shown that, compared to nonaligned scaffolds, aligned electrospun polymer scaffolds exhibit greater anisotropy and exert a greater tenogenic effect. Nevertheless, achieving rapid cell infiltration through the full thickness of the scaffold is challenging, and scaling to a translationally relevant size may be difficult. Our goal was to evaluate whether a novel method of alignment, combining a multilayered electrospinning technique with a hybrid of several electrospinning alignment techniques, would permit cell infiltration and collagen deposition through the thickness of poly(ε-caprolactone) scaffolds following seeding with human adipose-derived stem cells. Furthermore, we evaluated whether multilayered aligned scaffolds enhanced collagen alignment, tendon-related gene expression, and mechanical properties compared to multilayered nonaligned scaffolds. Both aligned and nonaligned multilayered scaffolds demonstrated cell infiltration and ECM deposition through the full thickness of the scaffold after only 28days of culture. Aligned scaffolds displayed significantly increased expression of tenomodulin compared to nonaligned scaffolds and exhibited aligned collagen fibrils throughout the full thickness, the presence of which may account for the increased yield stress and Young's modulus of cell-seeded aligned scaffolds along the axis of fiber alignment.
  
  
  CONCLUSIONS
  Rotator cuff tears are an important clinical problem in the shoulder, with over 300,000 surgical repairs performed annually. Re-tear rates may be high, and current methods used to augment surgical repair have limited evidence to support their clinical use due to inadequate initial mechanical properties and slow cellular infiltration. Tissue engineering approaches such as electrospinning have shown similar challenges in previous studies. In this study, a novel technique to align electrospun fibers while using a multilayered approach demonstrated increased mechanical properties and development of aligned collagen through the full thickness of the scaffolds compared to nonaligned multilayered scaffolds, and both types of scaffolds demonstrated rapid cell infiltration through the full thickness of the scaffold.
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Orr
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
authors.forename: Abby
authors.initials: A
authors.lastname: Chainani
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Kirk J
authors.initials: KJ
authors.lastname: Hippensteel
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
authors.forename: Alysha
authors.initials: A
authors.lastname: Kishan
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Gilchrist
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
authors.forename: N William
authors.initials: NW
authors.lastname: Garrigues
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Ruch
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
authors.forename: Farshid
authors.initials: F
authors.lastname: Guilak
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: dianne.little@duke.edu.
authors.forename: Dianne
authors.initials: D
authors.lastname: Little
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry*; D006801:Humans; D011091:Polyesters / Q000737:chemistry*; D017006:Rotator Cuff; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D011091:Polyesters; C016240:polycaprolactone
keywords: Adipose-derived stem cell; Electrospinning; Microfiber; Nanofiber; Tissue engineering