title: Combined effects of chemical priming and mechanical stimulation on mesenchymal stem cell differentiation on nanofiber scaffolds.
abstract: Functional tissue engineering of connective tissues such as the anterior cruciate ligament (ACL) remains a significant clinical challenge, largely due to the need for mechanically competent scaffold systems for grafting, as well as a reliable cell source for tissue formation. We have designed an aligned, polylactide-co-glycolide (PLGA) nanofiber-based scaffold with physiologically relevant mechanical properties for ligament regeneration. The objective of this study is to identify optimal tissue engineering strategies for fibroblastic induction of human mesenchymal stem cells (hMSC), testing the hypothesis that basic fibroblast growth factor (bFGF) priming coupled with tensile loading will enhance hMSC-mediated ligament regeneration. It was observed that compared to the unloaded, as well as growth factor-primed but unloaded controls, bFGF stimulation followed by physiologically relevant tensile loading enhanced hMSC proliferation, collagen production and subsequent differentiation into ligament fibroblast-like cells, upregulating the expression of types I and III collagen, as well as tenasin-C and tenomodulin. The results of this study suggest that bFGF priming increases cell proliferation, while mechanical stimulation of the hMSCs on the aligned nanofiber scaffold promotes fibroblastic induction of these cells. In addition to demonstrating the potential of nanofiber scaffolds for hMSC-mediated functional ligament tissue engineering, this study yields new insights into the interactive effects of chemical and mechanical stimuli on stem cell differentiation.
authors.affiliation: Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA. Electronic address: sds2156@columbia.edu.
authors.forename: Siddarth D
authors.initials: SD
authors.lastname: Subramony
authors.affiliation: Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Su
authors.affiliation: Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Yeager
authors.affiliation: Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA; Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace Building, MC 8904, 1210 Amsterdam Avenue, New York, NY 10027, USA. Electronic address: hhlu@columbia.edu.
authors.forename: Helen H
authors.initials: HH
authors.lastname: Lu
mesh_terms: D016118:Anterior Cruciate Ligament / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D019344:Lactic Acid; D008565:Membrane Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D057139:Nanofibers; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012038:Regeneration; D013314:Stress, Mechanical; D019063:Tenascin / Q000378:metabolism; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D008565:Membrane Proteins; C422444:TNMD protein, human; D019063:Tenascin; D016222:Fibroblast Growth Factor 2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Basic fibroblast growth factor; Bioreactor; Functional tissue engineering; Ligament; Mechanical stimulation; Stem cells