title: A high throughput mechanical screening device for cartilage tissue engineering.
abstract: Articular cartilage enables efficient and near-frictionless load transmission, but suffers from poor inherent healing capacity. As such, cartilage tissue engineering strategies have focused on mimicking both compositional and mechanical properties of native tissue in order to provide effective repair materials for the treatment of damaged or degenerated joint surfaces. However, given the large number design parameters available (e.g. cell sources, scaffold designs, and growth factors), it is difficult to conduct combinatorial experiments of engineered cartilage. This is particularly exacerbated when mechanical properties are a primary outcome, given the long time required for testing of individual samples. High throughput screening is utilized widely in the pharmaceutical industry to rapidly and cost-effectively assess the effects of thousands of compounds for therapeutic discovery. Here we adapted this approach to develop a high throughput mechanical screening (HTMS) system capable of measuring the mechanical properties of up to 48 materials simultaneously. The HTMS device was validated by testing various biomaterials and engineered cartilage constructs and by comparing the HTMS results to those derived from conventional single sample compression tests. Further evaluation showed that the HTMS system was capable of distinguishing and identifying 'hits', or factors that influence the degree of tissue maturation. Future iterations of this device will focus on reducing data variability, increasing force sensitivity and range, as well as scaling-up to even larger (96-well) formats. This HTMS device provides a novel tool for cartilage tissue engineering, freeing experimental design from the limitations of mechanical testing throughput.
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Mohanraj
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Chieh
authors.initials: C
authors.lastname: Hou
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Meloni
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Collaborative Research Partner Acute Cartilage Injury Program of AO Foundation, Davos, Switzerland.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Cosgrove
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Collaborative Research Partner Acute Cartilage Injury Program of AO Foundation, Davos, Switzerland.
authors.forename: George R
authors.initials: GR
authors.lastname: Dodge
authors.affiliation: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Collaborative Research Partner Acute Cartilage Injury Program of AO Foundation, Davos, Switzerland; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address: lemauck@mail.med.upenn.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Mauck
mesh_terms: D001672:Biocompatible Materials; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials
keywords: 3D culture; High throughput screening; Mechanical testing