{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:06:15Z","timestamp":1790863575142,"version":"4.1.0"},"reference-count":28,"publisher":"ASME International","issue":"11","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.asme.org\/publications-submissions\/publishing-information\/legal-policies"}],"content-domain":{"domain":["asmedigitalcollection.asme.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A heart valve leaflet flexes tens of millions of times each year inside a fluid carrying active collagenases, yet its collagen network holds for decades before disease unravels it within months. This review argues the resolving principle is mechanical. Tensile strain reshapes the collagen triple helix and folds its scissile bond away from matrix metalloproteinases (MMPs), a protective behavior termed strain-stabilization. The mechanism is traced from reconstituted collagen and tendon to native semilunar valve leaflets under physiologically realistic biaxial loading. The organizing framework is a V-shaped force-degradation curve\u2014a schematic, cross-scale synthesis assembled from experiments that differ in enzyme type, length scale, and tissue system, rather than a single directly measured dose-response relationship. Enzymatic attack is rapid at zero strain, falls to a minimum under moderate physiological tension, and rises under pathological overload, where single-molecule measurements record a 100-fold increase in MMP-1 cleavage rate at \u223c10 pN. Two biaxial studies anchor the argument. Equibiaxial stretching of porcine leaflets accelerated collagenolysis, whereas loading matched to diastolic strain ratios suppressed it almost entirely. Crimp, fiber rotation, and heterogeneous recruitment govern how tissue-level strain reaches individual molecules and which arm of the V-curve a leaflet occupies. Glutaraldehyde-fixed bioprosthetic valves fail by this logic inverted: fixation freezes the helix, disables the protective cycle, and strips glycosaminoglycans from the interfibrillary space before implantation. Conditioning tissue-engineered scaffolds under physiological biaxial strain produces collagen anisotropy matching native leaflets and tunes valve interstitial cell biosynthesis toward a homeostatic phenotype. Loading is a design variable, and the converging evidence reviewed here suggests that a valve can in principle be engineered to maintain its collagen in the protected regime\u2014a hypothesis that tissue-engineering studies are now beginning to test experimentally.<\/jats:p>","DOI":"10.1115\/1.4072712","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:35:09Z","timestamp":1789641309000},"update-policy":"https:\/\/doi.org\/10.1115\/crossmarkpolicy-asme","source":"Crossref","is-referenced-by-count":0,"title":["Strain-Stabilization of Collagen in Heart Valve Tissues: A Biomechanical Account of Proteolysis"],"prefix":"10.1115","volume":"148","author":[{"given":"Hsiao-Ying Shadow","family":"Huang","sequence":"first","affiliation":[{"name":"Mechanical and Aerospace Engineering Department, North Carolina State University , 1840 Entrepreneur Dr. , Raleigh, NC 27695"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyao","family":"Huang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04tj63d06","id-type":"ROR","asserted-by":"publisher"}],"name":"North Carolina State University Mechanical and Aerospace Engineering Department, , 1840 Entrepreneur Dr. , Raleigh, NC 27695"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Barbour","sequence":"additional","affiliation":[{"name":"Mechanical and Aerospace Engineering Department, North Carolina State University , 1840 Entrepreneur Dr. , Raleigh, NC 27695"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"33","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"issue":"1","key":"2026100109143372100_bib1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/jbm.820110113","article-title":"Mechanochemical Studies of Enzymatic Degradation of Insoluble Collagen Fibers","volume":"11","year":"1977","journal-title":"J. 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