Abstract

Tendinopathy is a leading cause of mobility issues. Currently, the cell–matrix interactions involved in the development of tendinopathy are not fully understood. In vitro tendon models provide a unique tool for addressing this knowledge gap as they permit fine control over biochemical, micromechanical, and structural aspects of the local environment to explore cell–matrix interactions. In this study, direct-write, near-field electrospinning of gelatin solution was implemented to fabricate micron-scale fibrous scaffolds that mimic native collagen fiber size and orientation. The stiffness of these fibrous scaffolds was found to be controllable between 1 MPa and 8 MPa using different crosslinking methods (EDC, DHT, DHT+EDC) or through altering the duration of crosslinking with EDC (1 h to 24 h). EDC crosslinking provided the greatest fiber stability, surviving up to 3 weeks in vitro. Differences in stiffness resulted in phenotypic changes for equine tenocytes with low stiffness fibers (∼1 MPa) promoting an elongated nuclear aspect ratio while those on high stiffness fibers (∼8 MPa) were rounded. High stiffness fibers resulted in the upregulation of matrix metalloproteinase (MMPs) and proteoglycans (possible indicators for tendinopathy) relative to low stiffness fibers. These results demonstrate the feasibility of direct-written gelatin scaffolds as tendon in vitro models and provide evidence that matrix mechanical properties may be crucial factors in cell–matrix interactions during tendinopathy formation.

References

1.
Vasiliadis
,
A. V.
, and
Katakalos
,
K.
,
2020
, “
The Role of Scaffolds in Tendon Tissue Engineering
,”
J. Funct. Biomater.
,
11
(
4
), p.
78
.10.3390/jfb11040078
2.
Theodossiou
,
S. K.
, and
Schiele
,
N. R.
,
2019
, “
Models of Tendon Development and Injury
,”
BMC Biomed. Eng.
,
1
(
1
), p.
32
.10.1186/s42490-019-0029-5
3.
Sharma
,
P.
, and
Maffulli
,
N.
,
2005
, “
Tendon Injury and Tendinopathy: Healing and Repair
,”
J. Bone Jt. Surg. Am.
,
87
(
1
), pp.
187
202
.10.2106/JBJS.D.01850
4.
Wu
,
Y.
,
Han
,
Y.
,
Wong
,
Y. S.
, and
Fuh
,
J. Y. H.
,
2018
, “
Fibre-Based Scaffolding Techniques for Tendon Tissue Engineering
,”
J. Tissue Eng. Regener. Med.
,
12
(
7
), pp.
1798
1821
.10.1002/term.2701
5.
Abat
,
F.
,
Alfredson
,
H.
,
Cucchiarini
,
M.
,
Madry
,
H.
,
Marmotti
,
A.
,
Mouton
,
C.
,
Oliveira
,
J. M.
, et al.,
2017
, “
Current Trends in Tendinopathy: Consensus of the ESSKA Basic Science Committee. Part I: Biology, Biomechanics, Anatomy and an Exercise-Based Approach
,”
J. Exp. Orthop.
,
4
(
1
), p.
18
.10.1186/s40634-017-0092-6
6.
Dirks
,
R. C.
, and
Warden
,
S. J.
,
2011
, “
Models for the Study of Tendinopathy
,”
J. Musculoskeletal Neuronal Interact.
,
11
(
2
), pp.
141
149
.https://pubmed.ncbi.nlm.nih.gov/21625051/
7.
Riemersma
,
D. J.
, and
Schamhardt
,
H. C.
,
1985
, “
In Vitro Mechanical Properties of Equine Tendons in Relation to Cross-Sectional Area and Collagen Content
,”
Res. Vet. Sci.
,
39
(
3
), pp.
263
270
.10.1016/S0034-5288(18)31711-9
8.
Hast
,
M. W.
,
Zuskov
,
A.
, and
Soslowsky
,
L. J.
,
2014
, “
The Role of Animal Models in Tendon Research
,”
Bone Jt. Res.
,
3
(
6
), pp.
193
202
.10.1302/2046-3758.36.2000281
9.
Wunderli
,
S. L.
,
Blache
,
U.
, and
Snedeker
,
J. G.
,
2020
, “
Tendon Explant Models for Physiologically Relevant In Vitro Study of Tissue Biology – A Perspective
,”
Connect. Tissue Res.
,
61
(
3–4
), pp.
262
277
.10.1080/03008207.2019.1700962
10.
Meeremans
,
M.
,
Van de Walle
,
G. R.
,
Van Vlierberghe
,
S.
, and
De Schauwer
,
C.
,
2021
, “
The Lack of a Representative Tendinopathy Model Hampers Fundamental Mesenchymal Stem Cell Research
,”
Front. Cell Dev. Biol.
,
9
, p.
1051
.10.3389/fcell.2021.651164
11.
Millar
,
N. L.
,
Murrell
,
G. A. C.
, and
McInnes
,
I. B.
,
2017
, “
Inflammatory Mechanisms in Tendinopathy – Towards Translation
,”
Nat. Rev. Rheumatol.
,
13
(
2
), pp.
110
122
.10.1038/nrrheum.2016.213
12.
Benage
,
L. G.
,
Sweeney
,
J. D.
,
Giers
,
M. B.
, and
Balasubramanian
,
R.
,
2022
, “
Dynamic Load Model Systems of Tendon Inflammation and Mechanobiology
,”
Front. Bioeng. Biotechnol.
,
10
, p.
896336
.10.3389/fbioe.2022.896336
13.
Crowe
,
L. A. N.
,
Garcia Melchor
,
E.
,
Murrell
,
G. A. C.
,
McInnes
,
I. B.
,
Akbar
,
M.
, and
Millar
,
N. L.
,
2021
, “
Stromal ‘Activation’ Markers Do Not Confer Pathogenic Activity in Tendinopathy
,”
Transl. Sports Med.
,
4
(
2
), pp.
268
279
.10.1002/tsm2.204
14.
Calejo
,
I.
,
Labrador-Rached
,
C. J.
,
Gomez-Florit
,
M.
,
Docheva
,
D.
,
Reis
,
R. L.
,
Domingues
,
R. M. A.
, and
Gomes
,
M. E.
,
2022
, “
Bioengineered 3D Living Fibers as In Vitro Human Tissue Models of Tendon Physiology and Pathology
,”
Adv. Healthcsre Mater.
,
11
(
15
), p.
2102863
.10.1002/adhm.202102863
15.
Wang
,
T.
,
Chen
,
P.
,
Zheng
,
M.
,
Wang
,
A.
,
Lloyd
,
D.
,
Leys
,
T.
,
Zheng
,
Q.
, and
Zheng
,
M. H.
,
2018
, “
In Vitro Loading Models for Tendon Mechanobiology
,”
J. Orthop. Res.
,
36
(
2
), pp.
566
575
.10.1002/jor.23752
16.
Howell
,
K.
,
Chien
,
C.
,
Bell
,
R.
,
Laudier
,
D.
,
Tufa
,
S. F.
,
Keene
,
D. R.
,
Andarawis-Puri
,
N.
, and
Huang
,
A. H.
,
2017
, “
Novel Model of Tendon Regeneration Reveals Distinct Cell Mechanisms Underlying Regenerative and Fibrotic Tendon Healing
,”
Sci. Rep.
,
7
(
1
), p.
45238
.10.1038/srep45238
17.
Lui
,
P. P. Y.
,
Maffulli
,
N.
,
Rolf
,
C.
, and
Smith
,
R. K. W.
,
2011
, “
What Are the Validated Animal Models for Tendinopathy?
,”
Scand. J. Med. Sci. Sports
,
21
(
1
), pp.
3
17
.10.1111/j.1600-0838.2010.01164.x
18.
Ryma
,
M.
,
Tylek
,
T.
,
Liebscher
,
J.
,
Blum
,
C.
,
Fernandez
,
R.
,
Böhm
,
C.
,
Kastenmüller
,
W.
,
Gasteiger
,
G.
, and
Groll
,
J.
,
2021
, “
Translation of Collagen Ultrastructure to Biomaterial Fabrication for Material-Independent but Highly Efficient Topographic Immunomodulation
,”
Adv. Mater.
,
33
(
33
), p.
2101228
.10.1002/adma.202101228
19.
Chen
,
Z.
,
Zhou
,
B.
,
Wang
,
X.
,
Zhou
,
G.
,
Zhang
,
W.
,
Yi
,
B.
,
Wang
,
W.
, and
Liu
,
W.
,
2022
, “
Synergistic Effects of Mechanical Stimulation and Crimped Topography to Stimulate Natural Collagen Development for Tendon Engineering
,”
Acta Biomater.
,
145
, pp.
297
315
.10.1016/j.actbio.2022.04.026
20.
Fan
,
X.
,
2019
, “
Development and Characterization of a Biopolymer Direct-Write Process for 3D Microvascular Structures Formation
,”
Electronic theses and dissertations
, University of Louisville, Louisville, KY.10.18297/etd/3335
21.
Fuh
,
Y.-K.
,
Wu
,
Y.-C.
,
He
,
Z.-Y.
,
Huang
,
Z.-M.
, and
Hu
,
W.-W.
,
2016
, “
The Control of Cell Orientation Using Biodegradable Alginate Fibers Fabricated by Near-Field Electrospinning
,”
Mater. Sci. Eng. C
,
62
, pp.
879
887
.10.1016/j.msec.2016.02.028
22.
Santschi
,
M.
,
Vernengo
,
A.
,
Eglin
,
D.
,
D'Este
,
M.
, and
Wuertz-Kozak
,
K.
,
2019
, “
Decellularized Matrix as a Building Block in Bioprinting and Electrospinning
,”
Curr. Opin. Biomed. Eng.
,
10
, pp.
116
122
.10.1016/j.cobme.2019.05.003
23.
Gilchrist
,
C. L.
,
Ruch
,
D. S.
,
Little
,
D.
, and
Guilak
,
F.
,
2014
, “
Micro-Scale and Meso-Scale Architectural Cues Cooperate and Compete to Direct Aligned Tissue Formation
,”
Biomaterials
,
35
(
38
), pp.
10015
10024
.10.1016/j.biomaterials.2014.08.047
24.
Baldwin
,
M. J.
,
Mimpen
,
J. Y.
,
Cribbs
,
A. P.
,
Stace
,
E.
,
Philpott
,
M.
,
Dakin
,
S. G.
,
Carr
,
A. J.
, and
Snelling
,
S. J. B.
,
2022
, “
Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype Within Tendon Fibroblasts
,”
Front. Bioeng. Biotechnol.
,
9
, p.
795748
.10.3389/fbioe.2021.795748
25.
Dalby
,
M. J.
,
Gadegaard
,
N.
,
Tare
,
R.
,
Andar
,
A.
,
Riehle
,
M. O.
,
Herzyk
,
P.
,
Wilkinson
,
C. D. W.
, and
Oreffo
,
R. O. C.
,
2007
, “
The Control of Human Mesenchymal Cell Differentiation Using Nanoscale Symmetry and Disorder
,”
Nat. Mater.
,
6
(
12
), pp.
997
1003
.10.1038/nmat2013
26.
Morita
,
Y.
,
Sato
,
T.
,
Higashiura
,
K.
,
Hirano
,
Y.
,
Matsubara
,
F.
,
Oshima
,
K.
,
Niwa
,
K.
, et al.,
2019
, “
The Optimal Mechanical Condition in Stem Cell-to-Tenocyte Differentiation Determined With the Homogeneous Strain Distributions and the Cellular Orientation Control
,”
Biol. Open
,
8
(
5
), p.
bio039164
.10.1242/bio.039164
27.
Gomez-Florit
,
M.
,
Labrador-Rached
,
C. J.
,
Domingues
,
R. M. A.
, and
Gomes
,
M. E.
,
2022
, “
The Tendon Microenvironment: Engineered In Vitro Models to Study Cellular Crosstalk
,”
Adv. Drug Delivery Rev.
,
185
, p.
114299
.10.1016/j.addr.2022.114299
28.
Foolen
,
J.
,
Wunderli
,
S. L.
,
Loerakker
,
S.
, and
Snedeker
,
J. G.
,
2018
, “
Tissue Alignment Enhances Remodeling Potential of Tendon-Derived Cells - Lessons From a Novel Microtissue Model of Tendon Scarring
,”
Matrix Biol.
,
65
, pp.
14
29
.10.1016/j.matbio.2017.06.002
29.
Castilho
,
M.
,
Levato
,
R.
,
Bernal
,
P. N.
,
de Ruijter
,
M.
,
Sheng
,
C. Y.
,
van Duijn
,
J.
,
Piluso
,
S.
,
Ito
,
K.
, and
Malda
,
J.
,
2021
, “
Hydrogel-Based Bioinks for Cell Electrowriting of Well-Organized Living Structures With Micrometer-Scale Resolution
,”
Biomacromolecules
,
22
(
2
), pp.
855
866
.10.1021/acs.biomac.0c01577
30.
Aldana
,
A. A.
, and
Abraham
,
G. A.
,
2017
, “
Current Advances in Electrospun Gelatin-Based Scaffolds for Tissue Engineering Applications
,”
Int. J. Pharm.
,
523
(
2
), pp.
441
453
.10.1016/j.ijpharm.2016.09.044
31.
Guner
,
M. B.
,
Dalgic
,
A. D.
,
Tezcaner
,
A.
,
Yilanci
,
S.
, and
Keskin
,
D.
,
2020
, “
A Dual-Phase Scaffold Produced by Rotary Jet Spinning and Electrospinning for Tendon Tissue Engineering
,”
Biomed. Mater. Bristol Eng.
,
15
(
6
), p.
065014
.10.1088/1748-605X/ab9550
32.
Blum
,
C.
,
Schlegelmilch
,
K.
,
Schilling
,
T.
,
Shridhar
,
A.
,
Rudert
,
M.
,
Jakob
,
F.
,
Dalton
,
P. D.
,
Blunk
,
T.
,
Flynn
,
L. E.
, and
Groll
,
J.
,
2019
, “
Extracellular Matrix-Modified Fiber Scaffolds as a Proadipogenic Mesenchymal Stromal Cell Delivery Platform
,”
ACS Biomater. Sci. Eng.
,
5
(
12
), pp.
6655
6666
.10.1021/acsbiomaterials.9b00894
33.
Alexander
,
F. A.
,
Johnson
,
L.
,
Williams
,
K.
, and
Packer
,
K.
,
2019
, “
A Parameter Study for 3D-Printing Organized Nanofibrous Collagen Scaffolds Using Direct-Write Electrospinning
,”
Materials
,
12
(
24
), p.
4131
.10.3390/ma12244131
34.
Davis
,
Z.
,
Hussain
,
A. F.
, and
Fisher
,
M.
,
2021
, “
Processing Variables of Direct-Write, Near-Field Electrospinning Impact Size and Morphology of Gelatin Fibers
,”
Biomed. Mater.
,
16
(
4
), p.
045017
.10.1088/1748-605X/abf88b
35.
Wang
,
C.
,
Xu
,
Y.
,
Xia
,
J.
,
Zhou
,
Z.
,
Fang
,
Y.
,
Zhang
,
L.
, and
Sun
,
W.
,
2021
, “
Multi-Scale Hierarchical Scaffolds With Aligned Micro-Fibers for Promoting Cell Alignment
,”
Biomed. Mater. Bristol Eng.
,
16
(
4
), p.
045047
.10.1088/1748-605X/ac0a90
36.
Bello
,
A. B.
,
Kim
,
D.
,
Kim
,
D.
,
Park
,
H.
, and
Lee
,
S.-H.
,
2020
, “
Engineering and Functionalization of Gelatin Biomaterials: From Cell Culture to Medical Applications
,”
Tissue Eng. Part B Rev.
,
26
(
2
), pp.
164
180
.10.1089/ten.teb.2019.0256
37.
Grier
,
W. K.
,
Iyoha
,
E. M.
, and
Harley
,
B. A. C.
,
2017
, “
The Influence of Pore Size and Stiffness on Tenocyte Bioactivity and Transcriptomic Stability in Collagen-GAG Scaffolds
,”
J. Mech. Behav. Biomed. Mater.
,
65
, pp.
295
305
.10.1016/j.jmbbm.2016.08.034
38.
Patel
,
D.
,
Sharma
,
S.
,
Screen
,
H. R. C.
, and
Bryant
,
S. J.
,
2018
, “
Effects of Cell Adhesion Motif, Fiber Stiffness, and Cyclic Strain on Tenocyte Gene Expression in a Tendon Mimetic Fiber Composite Hydrogel
,”
Biochem. Biophys. Res. Commun.
,
499
(
3
), pp.
642
647
.10.1016/j.bbrc.2018.03.203
39.
Ghassemi
,
Z.
, and
Slaughter
,
G.
,
2018
, “
Storage Stability of Electrospun Pure Gelatin Stabilized With EDC/Sulfo-NHS
,”
Biopolymers
,
109
(
9
), p.
e23232
.10.1002/bip.23232
40.
Campiglio
,
C. E.
,
Ponzini
,
S.
,
De Stefano
,
P.
,
Ortoleva
,
G.
,
Vignati
,
L.
, and
Draghi
,
L.
,
2020
, “
Cross-Linking Optimization for Electrospun Gelatin: Challenge of Preserving Fiber Topography
,”
Polymers
,
12
(
11
), p.
2472
.10.3390/polym12112472
41.
Haugh
,
M. G.
,
Jaasma
,
M. J.
, and
O'Brien
,
F. J.
,
2009
, “
The Effect of Dehydrothermal Treatment on the Mechanical and Structural Properties of Collagen-GAG Scaffolds
,”
J. Biomed. Mater. Res. A
,
89A
(
2
), pp.
363
369
.10.1002/jbm.a.31955
42.
Crowder
,
S. W.
,
Leonardo
,
V.
,
Whittaker
,
T.
,
Papathanasiou
,
P.
, and
Stevens
,
M. M.
,
2016
, “
Material Cues as Potent Regulators of Epigenetics and Stem Cell Function
,”
Cell Stem Cell
,
18
(
1
), pp.
39
52
.10.1016/j.stem.2015.12.012
43.
Engler
,
A. J.
,
Sen
,
S.
,
Sweeney
,
H. L.
, and
Discher
,
D. E.
,
2006
, “
Matrix Elasticity Directs Stem Cell Lineage Specification
,”
Cell
,
126
(
4
), pp.
677
689
.10.1016/j.cell.2006.06.044
44.
Rehmann
,
M. S.
,
Luna
,
J. I.
,
Maverakis
,
E.
, and
Kloxin
,
A. M.
,
2016
, “
Tuning Microenvironment Modulus and Biochemical Composition Promotes Human Mesenchymal Stem Cell Tenogenic Differentiation
,”
J. Biomed. Mater. Res. A
,
104
(
5
), pp.
1162
1174
.10.1002/jbm.a.35650
45.
Ratanavaraporn
,
J.
,
Rangkupan
,
R.
,
Jeeratawatchai
,
H.
,
Kanokpanont
,
S.
, and
Damrongsakkul
,
S.
,
2010
, “
Influences of Physical and Chemical Crosslinking Techniques on Electrospun Type a and B Gelatin Fiber Mats
,”
Int. J. Biol. Macromol.
,
47
(
4
), pp.
431
438
.10.1016/j.ijbiomac.2010.06.008
46.
Reddy
,
N.
,
Reddy
,
R.
, and
Jiang
,
Q.
,
2015
, “
Crosslinking Biopolymers for Biomedical Applications
,”
Trends Biotechnol.
,
33
(
6
), pp.
362
369
.10.1016/j.tibtech.2015.03.008
47.
Kuijpers
,
A. J.
,
Engbers
,
G. H. M.
,
Feijen
,
J.
,
De Smedt
,
S. C.
,
Meyvis
,
T. K. L.
,
Demeester
,
J.
,
Krijgsveld
,
J.
,
Zaat
,
S. A. J.
, and
Dankert
,
J.
,
1999
, “
Characterization of the Network Structure of Carbodiimide Cross-Linked Gelatin Gels
,”
Macromolecules
,
32
(
10
), pp.
3325
3333
.10.1021/ma981929v
48.
Campiglio
,
C. E.
,
Contessi Negrini
,
N.
,
Farè
,
S.
, and
Draghi
,
L.
,
2019
, “
Cross-Linking Strategies for Electrospun Gelatin Scaffolds
,”
Materials
,
12
(
15
), p.
24
.10.3390/ma12152476
49.
Oryan
,
A.
,
Kamali
,
A.
,
Moshiri
,
A.
,
Baharvand
,
H.
, and
Daemi
,
H.
,
2018
, “
Chemical Crosslinking of Biopolymeric Scaffolds: Current Knowledge and Future Directions of Crosslinked Engineered Bone Scaffolds
,”
Int. J. Biol. Macromol.
,
107
(
Pt A
), pp.
678
688
.10.1016/j.ijbiomac.2017.08.184
50.
Koch
,
D. W.
,
Schnabel
,
L. V.
,
Ellis
,
I. M.
,
Bates
,
R. E.
, and
Berglund
,
A. K.
,
2022
, “
TGF-Β2 Enhances Expression of Equine Bone Marrow-Derived Mesenchymal Stem Cell Paracrine Factors With Known Associations to Tendon Healing
,”
Stem Cell Res. Ther.
,
13
(
1
), p.
477
.10.1186/s13287-022-03172-9
51.
Falk
,
M.
,
Willing
,
E.
,
Schmidt
,
S.
,
Schatz
,
S.
,
Galster
,
M.
,
Tiemann
,
M.
,
Ficker
,
J. H.
, and
Brueckl
,
W. M.
,
2023
, “
Response of an HER2-Mutated NSCLC Patient to Trastuzumab Deruxtecan and Monitoring of Plasma ctDNA Levels by Liquid Biopsy
,”
Curr. Oncol.
,
30
(
2
), pp.
1692
1698
.10.3390/curroncol30020130
52.
Ionescu
,
L. C.
,
Lee
,
G. C.
,
Garcia
,
G. H.
,
Zachry
,
T. L.
,
Shah
,
R. P.
,
Sennett
,
B. J.
, and
Mauck
,
R. L.
,
2011
, “
Maturation State-Dependent Alterations in Meniscus Integration: Implications for Scaffold Design and Tissue Engineering
,”
Tissue Eng. Part A
,
17
(
1–2
), pp.
193
204
.10.1089/ten.tea.2010.0272
53.
Stegemann
,
H.
, and
Stalder
,
K.
,
1967
, “
Determination of Hydroxyproline
,”
Clin. Chim. Acta
,
18
(
2
), pp.
267
273
.10.1016/0009-8981(67)90167-2
54.
Neuman
,
R. E.
, and
Logan
,
M. A.
,
1950
, “
The Determination of Hydroxyproline
,”
J. Biol. Chem.
,
184
(
1
), pp.
299
306
.10.1016/S0021-9258(19)51149-8
55.
Fisher
,
M. B.
,
Henning
,
E. A.
,
Söegaard
,
N.
,
Bostrom
,
M.
,
Esterhai
,
J. L.
, and
Mauck
,
R. L.
,
2015
, “
Engineering Meniscus Structure and Function Via Multi-Layered Mesenchymal Stem Cell-Seeded Nanofibrous Scaffolds
,”
J. Biomech.
,
48
(
8
), pp.
1412
1419
.10.1016/j.jbiomech.2015.02.036
56.
Farndale
,
R. W.
,
Buttle
,
D. J.
, and
Barrett
,
A. J.
,
1986
, “
Improved Quantitation and Discrimination of Sulphated Glycosaminoglycans by Use of Dimethylmethylene Blue
,”
Biochim. Biophys. Acta BBA - Gen. Subj.
,
883
(
2
), pp.
173
177
.10.1016/0304-4165(86)90306-5
57.
Xu
,
Y.
, and
Murrell
,
G. A. C.
,
2008
, “
The Basic Science of Tendinopathy
,”
Clin. Orthop.
,
466
(
7
), pp.
1528
1538
.10.1007/s11999-008-0286-4
58.
Dulnik
,
J.
, and
Sajkiewicz
,
P.
,
2021
, “
Crosslinking of Gelatin in Bicomponent Electrospun Fibers
,”
Materials
,
14
(
12
), p.
3391
.10.3390/ma14123391
59.
Ahmad
,
Z.
,
Shepherd
,
J. H.
,
Shepherd
,
D. V.
,
Ghose
,
S.
,
Kew
,
S. J.
,
Cameron
,
R. E.
,
Best
,
S. M.
,
Brooks
,
R. A.
,
Wardale
,
J.
, and
Rushton
,
N.
,
2015
, “
Effect of 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodiimide and N-Hydroxysuccinimide Concentrations on the Mechanical and Biological Characteristics of Cross-Linked Collagen Fibres for Tendon Repair
,”
Regener. Biomater.
,
2
(
2
), pp.
77
85
.10.1093/rb/rbv005
60.
Nong
,
L.-M.
,
Zhou
,
D.
,
Zheng
,
D.
,
Jiang
,
Y.-Q.
,
Xu
,
N.-W.
,
Zhao
,
G.-Y.
,
Wei
,
H.
,
Zhou
,
S.-Y.
,
Han
,
H.
, and
Han
,
L.
,
2019
, “
The Effect of Different Cross-Linking Conditions of EDC/NHS on Type II Collagen Scaffolds: An In Vitro Evaluation
,”
Cell Tissue Banking
,
20
(
4
), pp.
557
568
.10.1007/s10561-019-09790-7
61.
Puetzer
,
J. L.
,
Ma
,
T.
,
Sallent
,
I.
,
Gelmi
,
A.
, and
Stevens
,
M. M.
,
2021
, “
Driving Hierarchical Collagen Fiber Formation for Functional Tendon, Ligament, and Meniscus Replacement
,”
Biomaterials
,
269
, p.
120527
.10.1016/j.biomaterials.2020.120527
62.
Sharma
,
R. I.
, and
Snedeker
,
J. G.
,
2010
, “
Biochemical and Biomechanical Gradients for Directed Bone Marrow Stromal Cell Differentiation Toward Tendon and Bone
,”
Biomaterials
,
31
(
30
), pp.
7695
7704
.10.1016/j.biomaterials.2010.06.046
63.
Ostadi Moghaddam
,
A.
,
Arshee
,
M. R.
,
Lin
,
Z.
,
Sivaguru
,
M.
,
Phillips
,
H.
,
McFarlin
,
B. L.
,
Toussaint
,
K. C.
, and
Wagoner Johnson
,
A. J.
,
2023
, “
Orientation-Dependent Indentation Reveals the Crosslink-Mediated Deformation Mechanisms of Collagen Fibrils
,”
Acta Biomater.
,
158
, pp.
347
357
.10.1016/j.actbio.2023.01.005
64.
Varma
,
S.
,
Orgel
,
J. P. R. O.
, and
Schieber
,
J. D.
,
2016
, “
Nanomechanics of Type I Collagen
,”
Biophys. J.
,
111
(
1
), pp.
50
56
.10.1016/j.bpj.2016.05.038
65.
Heim
,
A. J.
,
Matthews
,
W. G.
, and
Koob
,
T. J.
,
2006
, “
Determination of the Elastic Modulus of Native Collagen Fibrils Via Radial Indentation
,”
Appl. Phys. Lett.
,
89
(
18
), p.
181902
.10.1063/1.2367660
66.
Wenger
,
M. P. E.
,
Bozec
,
L.
,
Horton
,
M. A.
, and
Mesquida
,
P.
,
2007
, “
Mechanical Properties of Collagen Fibrils
,”
Biophys. J.
,
93
(
4
), pp.
1255
1263
.10.1529/biophysj.106.103192
67.
Yang
,
L.
,
Fitié
,
C. F. C.
,
van der Werf
,
K. O.
,
Bennink
,
M. L.
,
Dijkstra
,
P. J.
, and
Feijen
,
J.
,
2008
, “
Mechanical Properties of Single Electrospun Collagen Type I Fibers
,”
Biomaterials
,
29
(
8
), pp.
955
962
.10.1016/j.biomaterials.2007.10.058
68.
Yi
,
B.
,
Xu
,
Q.
, and
Liu
,
W.
,
2022
, “
An Overview of Substrate Stiffness Guided Cellular Response and Its Applications in Tissue Regeneration
,”
Bioact. Mater.
,
15
, pp.
82
102
.10.1016/j.bioactmat.2021.12.005
69.
Schoenenberger
,
A. D.
,
Foolen
,
J.
,
Moor
,
P.
,
Silvan
,
U.
, and
Snedeker
,
J. G.
,
2018
, “
Substrate Fiber Alignment Mediates Tendon Cell Response to Inflammatory Signaling
,”
Acta Biomater.
,
71
, pp.
306
317
.10.1016/j.actbio.2018.03.004
70.
Arya
,
S.
, and
Kulig
,
K.
,
2010
, “
Tendinopathy Alters Mechanical and Material Properties of the Achilles Tendon
,”
J. Appl. Physiol.
,
108
(
3
), pp.
670
675
.10.1152/japplphysiol.00259.2009
71.
Freedman
,
B. R.
,
Knecht
,
R. S.
,
Tinguely
,
Y.
,
Eskibozkurt
,
G. E.
,
Wang
,
C. S.
, and
Mooney
,
D. J.
,
2022
, “
Aging and Matrix Viscoelasticity Affect Multiscale Tendon Properties and Tendon Derived Cell Behavior
,”
Acta Biomater.
,
143
, pp.
63
71
.10.1016/j.actbio.2022.03.006
72.
Gouldin
,
A. G.
,
Brown
,
M. E.
, and
Puetzer
,
J. L.
,
2021
, “
An Inducible Model for Unraveling the Effects of Advanced Glycation End-Product Accumulation in Aging Connective Tissues
,”
Connect. Tissue Res.
,
63
(
4
), pp.
406
424
.10.1080/03008207.2021.1991333
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