title: Fibrous Scaffolds with Varied Fiber Chemistry and Growth Factor Delivery Promote Repair in a Porcine Cartilage Defect Model.
abstract: Current clinically approved methods for cartilage repair are generally based on either endogenous cell recruitment (e.g., microfracture) or chondrocyte delivery (e.g., autologous chondrocyte implantation). However, both methods culminate in repair tissue with inferior mechanical properties and the addition of biomaterials to these clinical interventions may improve their efficacy. To this end, the objective of this study was to investigate the ability of multipolymer acellular fibrous scaffolds to improve cartilage repair when combined with microfracture in a large animal (i.e., minipig) model. Composite scaffolds were formulated from a combination of hyaluronic acid (HA) fibers and poly(ɛ-caprolactone) (PCL) fibers, either with or without transforming growth factor-β3 (TGFβ3). After 12 weeks in vivo, material choice and TGFβ3 delivery had a significant impact on outcomes; specifically, PCL scaffolds without TGFβ3 had inferior gross appearance and reduced mechanical properties, whereas HA scaffolds that released TGFβ3 resulted in improved histological scores and increased type 2 collagen content. Importantly, analysis of the overall dataset revealed that histology, but not gross appearance, was a better predictor of mechanical properties. This study highlights the importance of scaffold properties on in vivo cartilage repair as well as the need for numerous quantitative outcome measures to fully evaluate treatment methods.
authors.affiliation: 1 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.|2 Translational Musculoskeletal Research Center, Philadelphia VA Medical Center , Philadelphia, Pennsylvania.
authors.forename: Iris L
authors.initials: IL
authors.lastname: Kim
authors.affiliation: 2 Translational Musculoskeletal Research Center, Philadelphia VA Medical Center , Philadelphia, Pennsylvania.|3 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Pfeifer
authors.affiliation: 2 Translational Musculoskeletal Research Center, Philadelphia VA Medical Center , Philadelphia, Pennsylvania.|3 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Fisher
authors.affiliation: 2 Translational Musculoskeletal Research Center, Philadelphia VA Medical Center , Philadelphia, Pennsylvania.|3 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Vishal
authors.initials: V
authors.lastname: Saxena
authors.affiliation: 2 Translational Musculoskeletal Research Center, Philadelphia VA Medical Center , Philadelphia, Pennsylvania.|3 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Meloni
authors.affiliation: 1 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Mi Y
authors.initials: MY
authors.lastname: Kwon
authors.affiliation: 2 Translational Musculoskeletal Research Center, Philadelphia VA Medical Center , Philadelphia, Pennsylvania.|3 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Minwook
authors.initials: M
authors.lastname: Kim
authors.affiliation: 2 Translational Musculoskeletal Research Center, Philadelphia VA Medical Center , Philadelphia, Pennsylvania.|3 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: David R
authors.initials: DR
authors.lastname: Steinberg
authors.affiliation: 1 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.|2 Translational Musculoskeletal Research Center, Philadelphia VA Medical Center , Philadelphia, Pennsylvania.|3 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Mauck
authors.affiliation: 1 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.|2 Translational Musculoskeletal Research Center, Philadelphia VA Medical Center , Philadelphia, Pennsylvania.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Burdick
mesh_terms: D000818:Animals; D019245:Compressive Strength; D004343:Drug Implants / Q000008:administration & dosage; D019544:Equipment Failure Analysis; D050724:Fractures, Cartilage / Q000473:pathology* / Q000628:therapy*; D048091:Guided Tissue Regeneration / Q000295:instrumentation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000737:chemistry; D008422:Materials Testing; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D011474:Prosthesis Design; D013314:Stress, Mechanical; D013552:Swine; D013556:Swine, Miniature; D013718:Tensile Strength; D054457:Tissue Scaffolds; D053782:Transforming Growth Factor beta3 / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D004343:Drug Implants; D036341:Intercellular Signaling Peptides and Proteins; D053782:Transforming Growth Factor beta3