title: Anterior cruciate ligament regeneration using braided biodegradable scaffolds: in vitro optimization studies.
abstract: The anterior cruciate ligament (ACL) is the most commonly injured intra-articular ligament of the knee, and limitations in existing reconstruction grafts have prompted an interest in tissue engineered solutions. Previously, we reported on a tissue-engineered ACL scaffold fabricated using a novel, three-dimensional braiding technology. A critical factor in determining cellular response to such a graft is material selection. The objective of this in vitro study was to optimize the braided scaffold, focusing on material composition and the identification of an appropriate polymer. The selection criteria are based on cellular response, construct degradation, and the associated mechanical properties. Three compositions of poly-alpha-hydroxyester fibers, namely polyglycolic acid (PGA), poly-L-lactic acid (PLLA), and polylactic-co-glycolic acid 82:18 (PLAGA) were examined. The effects of polymer composition on scaffold mechanical properties and degradation were evaluated in physiologically relevant solutions. Prior to culturing with primary rabbit ACL cells, scaffolds were pre-coated with fibronectin (Fn, PGA-Fn, PLAGA-Fn, PLLA-Fn), an important protein which is upregulated during ligament healing. Cell attachment and growth were examined as a function of time and polymer composition. While PGA scaffolds measured the highest tensile strength followed by PLLA and PLAGA, its rapid degradation in vitro resulted in matrix disruption and cell death over time. PLLA-based scaffolds maintained their structural integrity and exhibited superior mechanical properties over time. The response of ACL cells was found to be dependent on polymer composition, with the highest cell number measured on PLLA-Fn scaffolds. Surface modification of polymer scaffolds with Fn improved cell attachment efficiency and effected the long-term matrix production by ACL cells on PLLA and PLAGA scaffolds. Therefore based on the overall cellular response and its temporal mechanical and degradation properties in vitro, the PLLA braided scaffold pre-coated with Fn was found to be the most suitable substrate for ACL tissue engineering.
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
authors.forename: Helen H
authors.initials: HH
authors.lastname: Lu
authors.forename: James A
authors.initials: JA
authors.lastname: Cooper
authors.forename: Sharron
authors.initials: S
authors.lastname: Manuel
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Freeman
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Attawia
authors.forename: Frank K
authors.initials: FK
authors.lastname: Ko
authors.forename: Cato T
authors.initials: CT
authors.lastname: Laurencin
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000494:pharmacology; D004548:Elasticity; D005353:Fibronectins / Q000737:chemistry / Q000494:pharmacology; D048091:Guided Tissue Regeneration / Q000295:instrumentation / Q000379:methods*; D019344:Lactic Acid / Q000032:analysis / Q000737:chemistry*; D008422:Materials Testing; D011100:Polyglycolic Acid / Q000032:analysis / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000032:analysis / Q000737:chemistry*; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D013718:Tensile Strength
chemical_list: D020099:Coated Materials, Biocompatible; D005353:Fibronectins; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid