journal article·2026-03Open access

Dynamic and static strain levels differentially affect the enzymatic degradation of collagen fibres

Amal K. Mansoor, Mark C. van Turnhout, Keita Ito, Tommaso Ristori, Jasper Foolen

Acta Biomaterialia· Volume 213

Abstract

Collagen fibres are essential for the load-bearing capacity of soft biological tissues, ensuring structural integrity and function. The repair process after injury often involves collagen remodelling, including reorganisation, synthesis, and degradation. When remodelling is unbalanced, degradation can lead to mechanical strength loss and tissue failure, as often seen after anterior cruciate ligament reconstruction. It is well established that enzymatic collagen degradation is modulated by levels of static strain, with relatively low and high strain magnitudes accelerating degradation rates compared to an intermediate minimum. However, in vivo, load-bearing tissues experience more often dynamic strain, and the impact of different magnitudes of cyclic strain on collagen enzymatic breakdown remains unclear. The present study investigated whether different levels of cyclic strain alter the susceptibility of collagen to enzymatic degradation by collagenases, and compared them to static strain. Decellularised porcine patellar tendons underwent various static and cyclic strain relaxation tests with or without bacterial collagenases. Consistent with prior findings, static strain elicited maximum protection at the heel point where stiffness increases. In contrast, dynamic strain accelerated degradation regardless of average strain, indicating a magnitude-independent mechanism under dynamic loading. Additionally, the dynamic degradation rate, unlike under static stretch, was relatively unaffected in the toe region, with a decreasing trend above the heel point. These findings suggest that optimising tissue recovery with controlled collagen degradation requires carefully selecting strain values based on the loading type. Such insights enhance our understanding of collagen remodelling and inform recovery strategies. STATEMENT OF SIGNIFICANCE: Tissue repair after injury involves collagen remodelling, where degradation plays an important role. Collagen enzymatic degradation is known to be affected by static strain. However, in vivo tissues experience dynamic strains, with unclear effects. We investigated how dynamic strain alters collagen enzymatic degradation in porcine patellar tendons. As shown previously, static strain protected collagen degradation at the heel point, whereas the present study provided new insight that dynamic strain increased the degradation rate relative to static strain at all strain values and that this effect trended to be less sensitive to strain levels. These results suggest that physiological strains influence collagen degradation differently under static and dynamic loading, offering insights that may guide targeted strain applications to improve healing.
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Research context

OpenAlex topics: Tendon Structure and Treatment · Knee injuries and reconstruction techniques · Cellular Mechanics and Interactions

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (67)

Show source-provided references
1. Tissue repair: the hidden drama10.4161/org.6.4.12555 ↗
2. The roles of matrix metalloproteinases and their inhibitors in human diseases10.3390/ijms21249739 ↗
3. Tension in fibrils suppresses their enzymatic degradation – A molecular mechanism for ‘use it or lose it10.1016/j.matbio.2019.06.001 ↗
4. C. Huang, I.V Yannas, Mechanochemical studies of enzymatic degradation of insoluble collagen fibers, 154 (1977) 137–154.10.1002/jbm.820110113 ↗
5. Strain-controlled enzymatic cleavage of collagen in loaded matrix10.1016/j.bbrc.2005.08.128 ↗
6. Deformation-dependent enzyme mechanokinetic cleavage of type I collagen10.1115/1.3078177 ↗
7. Modulation of collagen fiber orientation by strain-controlled enzymatic degradation10.1016/j.actbio.2016.02.033 ↗
8. Uniaxial tension inhibits tendon collagen degradation by collagenase in vitro10.1002/jor.1100140120 ↗
9. Single-molecule tracking of collagenase on native type i collagen fibrils reveals degradation mechanism10.1016/j.cub.2012.04.012 ↗
10. Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis10.1073/pnas.0710588105 ↗
11. Small-angle light scattering to detect strain-directed collagen degradation in native tissue10.1098/rsfs.2011.0039 ↗
12. Highly sensitive single-fibril erosion assay demonstrates mechanochemical switch in native collagen fibrils10.1007/s10237-012-0399-2 ↗
13. Erratum: highly sensitive single-fibril erosion assay demonstrates mechanochemical switch in native collagen fibrils (Biomechanics and Modeling in Mechanobiology (2013) 12 (291300) DOI 10.1007/s10237-012-0399-2)10.1007/s10237-013-0500-5 ↗
14. Graft remodeling and ligamentization after anterior cruciate ligament reconstruction
15. Intra-articular remodelling of hamstring tendon grafts after anterior cruciate ligament reconstruction10.1007/s00167-013-2634-5 ↗
16. Postoperative healing and complications based on anterior cruciate ligament reconstruction graft type10.21037/aoj-24-3 ↗
17. Rehabilitation and return to sports after Achilles tendon repair10.26603/001c.122643 ↗
18. Anterior cruciate ligament graft positioning, tensioning and twisting10.1007/s001670050215 ↗
19. Review on tension in the natural and reconstructed anterior cruciate ligament10.1007/BF01845586 ↗
20. Effect of graft tensioning on mechanical restoration in a rat model of anterior cruciate ligament reconstruction using free tendon graft10.1007/s00167-012-1974-x ↗
21. The effect of initial graft tension on postoperative clinical outcome in anterior cruciate ligament reconstruction with semitendinosus tendon10.1007/s00402-005-0045-x ↗
22. Initial graft tension and the effect on postoperative patient functional outcomes in anterior cruciate ligament reconstruction10.1016/j.arthro.2013.01.021 ↗
23. The effect of initial graft tension on the biomechanical properties of a healing ACL replacement graft: a study in goats10.1016/S0736-0266(02)00265-6 ↗
24. Effects of complete stress-shielding on the mechanical properties and histology of in situ frozen patellar tendon10.1002/jor.1100110414 ↗
25. The effect of increased stress on the patellar tendon10.1302/0301-620X.84B3.0840440 ↗
26. An off-the-shelf decellularized and sterilized human bone-ACL-bone allograft for anterior cruciate ligament reconstruction10.1016/j.jmbbm.2022.105452 ↗
27. A decellularized and sterilized human meniscus allograft for off-the-shelf meniscus replacement10.1186/s40634-022-00555-y ↗
28. Decellularized porcine achilles tendon induces anti-inflammatory macrophage phenotype In vitro and tendon repair In vivo
29. Dynamic loading does not interfere with the initial repopulation of decellularized tendons: an ex vivo study10.1002/jbm.a.38005 ↗
30. Force measurements of the α5β1 integrin-fibronectin interaction10.1016/S0006-3495(03)74940-6 ↗
31. Stress relaxation of porcine tendon under simulated biological environment: experiment and modeling10.37190/ABB-01735-2020-02 ↗
32. Accumulation of collagen molecular unfolding is the mechanism of cyclic fatigue damage and failure in collagenous tissues10.1126/sciadv.aba2795 ↗
33. Ooomens · 2018
34. Optical clearing of fixed brain samples using SeeDB
35. SeeDB: A simple and morphology-preserving optical clearing agent for neuronal circuit reconstruction10.1038/nn.3447 ↗
36. M.-T. Ke, S. Fujimoto, T. Imai, Optical clearing using See DB, Bio Protocol 4 (2014). https://doi.org/10.21769/bioprotoc.1042.10.21769/BioProtoc.1042 ↗
37. How do I interpret a confidence interval?10.1111/trf.13635 ↗
38. Mechanical forces accelerate collagen digestion by bacterial collagenase in lung tissue strips10.3389/fphys.2016.00287 ↗
39. Mechanical strain enhances survivability of collagen micronetworks in the presence of collagenase: implications for load-bearing matrix growth and stability10.1098/rsta.2009.0093 ↗
40. Mechanical strain stabilizes reconstituted collagen fibrils against enzymatic degradation by mammalian collagenase matrix metalloproteinase 8 (MMP-8)10.1371/journal.pone.0012337 ↗
41. Probing collagen/enzyme mechanochemistry in native tissue with dynamic, enzyme-induced creep10.1021/la100384e ↗
42. Prediction of diffusion coefficients of plasmids10.1002/bit.21626 ↗
43. Molecular mechanochemistry: low force switch slows enzymatic cleavage of human type I collagen monomer10.1021/ja110098b ↗
44. Strain mediated enzymatic degradation of arterial tissue: insights into the role of the non-collagenous tissue matrix and collagen crimp10.1016/j.actbio.2018.06.037 ↗
45. Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides10.1038/ncomms14913 ↗
46. Tendon tissue microdamage and the limits of intrinsic repair10.1016/j.matbio.2019.07.008 ↗
47. Mechanical loading of bovine pericardium accelerates enzymatic degradation10.1016/S0142-9612(99)00013-7 ↗
48. Anterior cruciate ligament microfatigue damage detected by collagen autofluorescence in situ10.1186/s40634-022-00507-6 ↗
49. Mechanobiology of tendon10.1016/j.jbiomech.2005.05.011 ↗
50. From mechanical loading to collagen synthesis, structural changes and function in human tendon10.1111/j.1600-0838.2009.00986.x ↗
51. Pressure-induced collagen degradation in arterial tissue as a potential mechanism for degenerative arterial disease progression10.1016/j.jmbbm.2020.103771 ↗
52. Homeostatic collagen remodeling: enzymatic strain stabilization and large strain softening in pressurized thick-walled cylindrical vessels10.1007/s42558-024-00062-3 ↗
53. A computational analysis of cell-mediated compaction and collagen remodeling in tissue-engineered heart valves10.1016/j.jmbbm.2015.10.001 ↗
54. Cell-matrix interaction during straindependent remodelling of simulated collagen networks10.1098/rsfs.2015.0069 ↗
55. Computational modeling guides tissue-engineered heart valve design for long-term in vivo performance in a translational sheep model10.1126/scitranslmed.aan4587 ↗
56. Predicting and understanding collagen remodeling in human native heart valves during early development10.1016/j.actbio.2018.08.040 ↗
57. A physically motivated constitutive model for cell-mediated compaction and collagen remodeling in soft tissues10.1007/s10237-013-0549-1 ↗
58. Limited proteolysis of type I collagen at hyperreactive sites by class I and II Clostridium histolyticum collagenases: complementary digestion patterns10.1021/bi00377a004 ↗
59. Interstitial collagen catabolism10.1074/jbc.R113.451211 ↗
60. Diffusion tensor imaging in the musculoskeletal and peripheral nerve systems: from experimental to clinical applications10.1186/s41747-017-0018-1 ↗
61. Diffusion tensor imaging of tendons and ligaments at ultra-high magnetic fields10.1615/CritRevBiomedEng.2018027320 ↗
62. Tendon biomechanical properties are altered by storage duration but not freeze-thaw temperatures or cycles10.1002/jor.25783 ↗
63. The effect of multiple freeze-thaw cycles on the viscoelastic properties and microstructure of bovine superficial digital flexor tendon10.1016/j.jmbbm.2021.104582 ↗
64. A comparison of the quasi-static mechanical and non-linear viscoelastic properties of the human semitendinosus and gracilis tendons10.1016/j.clinbiomech.2009.12.007 ↗
65. Hydration dependent viscoelastic tensile behavior of cornea10.1007/s10439-014-0996-6 ↗
66. The effect of strain rate on the viscoelastic response of aortic valve tissue: A direct-fit approach10.1023/B:ABME.0000012742.01261.b0 ↗
67. Linear and quasi-linear viscoelastic characterization of ankle ligaments10.1115/1.429623 ↗