Dynamic tensile loading improves the functional properties of mesenchymal stem cell-laden nanofiber-based fibrocartilage.
Fibrocartilaginous tissues such as the meniscus serve critical load-bearing roles, relying on arrays of collagen fibers to resist tensile loads experienced with normal activity. As these structures are frequently injured and possess limited healing capacity, there exists great demand for tissue-engineered replacements. Toward recreating the structural features of these anisotropic tissues in vitro, we employ scaffolds composed of co-aligned nanofibers that direct mesenchymal stem cell (MSC) orientation and the formation of organized extracellular matrix (ECM). Concomitant with ECM synthesis, the mechanical properties of constructs increase with free-swelling culture, but ultimately failed to achieve equivalence with meniscal fibrocartilage. As mechanical forces are essential to the development and maintenance of musculoskeletal tissues, this work examined the effect of cyclic tensile loading on MSC-laden nanofibrous constructs. We hypothesized that loading would modulate the transcriptional behavior of MSCs, spur the deposition of ECM, and lead to enhancements in construct mechanical properties compared to free-swelling controls. Fiber-aligned scaffolds were seeded with MSCs and dynamically loaded daily in tension or maintained as nonloaded controls for 4 weeks. With mechanical stimulation, fibrous gene expression increased, collagen deposition increased, and the tensile modulus increased by 16% relative to controls. These results show that dynamic tensile loading enhances the maturation of MSC-laden aligned nanofibrous constructs, suggesting that recapitulation of the structural and mechanical environment of load-bearing tissues results in increases in functional properties that can be exploited for tissue engineering applications.
McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Brendon M
BM
Baker
Roshan P
RP
Shah
Alice H
AH
Huang
Robert L
RL
Mauck
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D051445:Fibrocartilage / Q000166:cytology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D057139:Nanofibers; D013718:Tensile Strength; D023822:Tissue Engineering
Anat Rec A Discov Mol Cell Evol Biol. 2004 May;278(1):428-36
15103737
Dev Cell. 2004 Apr;6(4):483-95
15068789
J Biomech. 1987;20(11-12):1095-109
3323201
J Biomech. 2003 Aug;36(8):1087-96
12831733
Clin Orthop Relat Res. 1999 Oct;(367 Suppl):S254-72
10546651
Arthroscopy. 2005 Feb;21(2):211-23
15689872
J Orthop Res. 1991 Sep;9(5):641-50
1870029
FEBS Lett. 1983 Jul 25;158(2):265-70
6688225
Annu Rev Biomed Eng. 2004;6:275-302
15255771
Arthritis Rheum. 2003 Aug;48(8):2178-87
12905471
J Biomech. 2007;40(8):1686-1693
17056048
Clin Orthop Relat Res. 1990 Mar;(252):8-18
2406077
Anat Embryol (Berl). 1998 Apr;197(4):317-24
9565324
Clin Orthop Relat Res. 1978 Mar-Apr;(131):279-87
657636
J Am Acad Orthop Surg. 2002 May-Jun;10(3):168-76
12041938
J Anat. 1998 Aug;193 ( Pt 2):161-78
9827632
J Biol Chem. 1950 May;184(1):299-306
15421999
Biomaterials. 2005 Apr;26(11):1261-70
15475056
Biomaterials. 2005 Sep;26(25):5158-66
15792543
Tissue Eng. 2005 Jul-Aug;11(7-8):1198-211
16144456
Tissue Eng Part A. 2010 Jun;16(6):1913-23
20088686
Biomaterials. 2006 Nov;27(32):5524-34
16859744
Development. 1998 Oct;125(20):4019-32
9735363
Cell Stem Cell. 2009 Jul 2;5(1):17-26
19570510
Tissue Eng. 2006 Aug;12(8):2291-300
16968169
Acta Biomater. 2011 Jan;7(1):57-66
20709198
Am J Pathol. 2003 Sep;163(3):1045-56
12937145
J Biomech Eng. 2000 Jun;122(3):252-60
10923293
Biomaterials. 2010 Aug;31(24):6190-200
20494438
Tissue Eng Part A. 2009 Nov;15(11):3461-72
19432533
Clin Biomech (Bristol, Avon). 1996 Jul;11(5):295-300
11415635
Clin Orthop Relat Res. 1990 Mar;(252):19-31
2406069
Ann Surg. 1931 Mar;93(3):649-82
17866518
J Rehabil Res Dev. 2000 Mar-Apr;37(2):127-33
10850818
Tissue Eng Part B Rev. 2009 Jun;15(2):171-93
19207040
Physiotherapy. 1976 Jun 10;62(7):223
989604
Biomech Model Mechanobiol. 2007 Jan;6(1-2):113-25
16691412
Cell. 2006 Aug 25;126(4):677-89
16923388
Osteoarthritis Cartilage. 2009 Mar;17(3):336-45
18848784
J Biomech Eng. 2000 Dec;122(6):570-5
11192376
Stem Cells. 2007 Mar;25(3):655-63
17124008
Science. 1999 Apr 2;284(5411):143-7
10102814
Biophys J. 2008 Aug;95(4):2116-24
18487290
Am J Sports Med. 2009 May;37(5):884-9
19336615
Biochim Biophys Acta. 1986 Sep 4;883(2):173-7
3091074
Clin Chim Acta. 1967 Nov;18(2):267-73
4864804
Osteoarthritis Cartilage. 2006 Feb;14(2):179-89
16257243
Am J Anat. 1976 Dec;147(4):407-17
1036868
Science. 2009 Jun 26;324(5935):1673-7
19556500
J Biomech Eng. 1983 Aug;105(3):216-25
6688842
Nat Mater. 2009 Dec;8(12):986-92
19855383
Br J Sports Med. 2000 Aug;34(4):252-7
10953895
Biomaterials. 2006 Jul;27(19):3631-8
16545867
Tissue Eng. 2003 Oct;9(5):967-79
14633381
Eur Cell Mater. 2010 Feb 26;19:72-85
20186667
Acta Biomater. 2011 Feb;7(2):485-91
20728589
Biomaterials. 2007 Apr;28(11):1967-77
17250888
Stem Cells. 2010 Mar 31;28(3):564-72
20082286
Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16095-100
17060641
Dev Cell. 2009 May;16(5):734-43
19460349
J Orthop Res. 2009 Mar;27(3):416-20
18924143