Anterior cruciate ligament microfatigue damage detected by collagen autofluorescence in situ

Abstract Purpose Certain types of repetitive sub-maximal knee loading cause microfatigue damage in the human anterior cruciate ligament (ACL) that can accumulate to produce macroscopic tissue failure. However, monitoring the progression of that ACL microfatigue damage as a function of loading cycles has not been reported. To explore the fatigue process, a confocal laser endomicroscope (CLEM) was employed to capture sub-micron resolution fluorescence images of the tissue in situ. The goal of this study was to quantify the in situ changes in ACL autofluorescence (AF) signal intensity and collagen microstructure as a function of the number of loading cycles. Methods Three paired and four single cadaveric knees were subjected to a repeated 4 times bodyweight landing maneuver known to strain the ACL. The paired knees were used to compare the development of ACL microfatigue damage on the loaded knee after 100 consecutive loading cycles, relative to the contralateral unloaded control knee, through second harmonic generation (SHG) and AF imaging using confocal microscopy (CM). The four single knees were used for monitoring progressive ACL microfatigue damage development by AF imaging using CLEM. Results The loaded knees from each pair exhibited a statistically significant increase in AF signal intensity and decrease in SHG signal intensity as compared to the contralateral control knees. Additionally, the anisotropy of the collagen fibers in the loaded knees increased as indicated by the reduced coherency coefficient. Two out of the four single knee ACLs failed during fatigue loading, and they exhibited an order of magnitude higher increase in autofluorescence intensity per loading cycle as compared to the intact knees. Of the three regions of the ACL - proximal, midsubstance and distal - the proximal region of ACL fibers exhibited the highest AF intensity change and anisotropy of fibers. Conclusions CLEM can capture changes in ACL AF and collagen microstructures in situ during and after microfatigue damage development. Results suggest a large increase in AF may occur in the final few cycles immediately prior to or at failure, representing a greater plastic deformation of the tissue. This reinforces the argument that existing microfatigue damage can accumulate to induce bulk mechanical failure in ACL injuries. The variation in fiber organization changes in the ACL regions with application of load is consistent with the known differences in loading distribution at the ACL femoral enthesis.http://deepblue.lib.umich.edu/bitstream/2027.42/173162/1/40634_2022_Article_507.pd

Fatigue-driven compliance increase and collagen unravelling in mechanically tested anterior cruciate ligament

Approximately 300,000 anterior cruciate ligament (ACL) tears occur annually in the United States, half of which lead to the onset of knee osteoarthritis within 10 years of injury. Repetitive loading is known to result in fatigue damage of both ligament and tendon in the form of collagen unravelling, which can lead to structural failure. However, the relationship between tissue's structural, compositional, and mechanical changes are poorly understood. Herein we show that repetitive submaximal loading of cadaver knees causes an increase in co-localised induction of collagen unravelling and tissue compliance, especially in regions of greater mineralisation at the ACL femoral enthesis. Upon 100 cycles of 4× bodyweight knee loading, the ACL exhibited greater unravelled collagen in highly mineralized regions across varying levels of stiffness domains as compared to unloaded controls. A decrease in the total area of the most rigid domain, and an increase in the total area of the most compliant domain was also found. The results highlight fatigue-driven changes in both protein structure and mechanics in the more mineralized regions of the ACL enthesis, a known site of clinical ACL failure. The results provide a starting point for designing studies to limit ligament overuse injury

Comprehensiveness of national bibliographic databases for social sciences and humanities : findings from a European survey

This article is based on work from COST Action 15137 European Network for Research Evaluation in the SSH (ENRESSH) and supported by COST (European Cooperation in Science and Technology). We thank all who have contributed to the two surveys on databases, especially Kasper Bruun, Gennady Eremenko, Viktor Glukhov, Marit Henningsen, Hanna-Mari Puuska, Svetlana Shabanova, Davor Šoštarič, and Mimi Urbanc. In the same way, we thank the reviewers for their valuable feedback.This article provides an overview of national bibliographic databases that include data on research output within social sciences and humanities (SSH) in Europe. We focus on the comprehensiveness of the database content. Compared to the data from commercial databases such as Web of Science and Scopus, data from national bibliographic databases (e.g. Flemish Academic Bibliographic Database for the SSH (VABB-SHW) in Belgium, Current Research Information System in Norway (CRISTIN)) are more comprehensive and may, therefore, be better fit for bibliometric analyses. Acknowledging this, several countries within Europe maintain national bibliographic databases; detailed and comparative information about their content, however, has been limited. In autumn 2016, we launched a survey to acquire an overview of national bibliographic databases for SSH in Europe and Israel. Surveying 41 countries (responses received from 39 countries), we identified 21 national bibliographic databases for SSH. Further, we acquired a more detailed description of 13 databases, with a focus on their comprehensiveness. Findings indicate that even though the content of national bibliographic databases is diverse, it is possible to delineate a subset that is similar across databases. At the same time, it is apparent that differences in national bibliographic databases are often bound to differences in country-specific arrangements. Considering this, we highlight implications to bibliometric analyses based on data from national bibliographic databases and outline several aspects that may be taken into account in the development of existing national bibliographic databases for SSH or the design of new ones.This work was supported by funding provided by the Flemish government to L.S., R.G., T.E., through the Centre for R&D Monitoring (ECOOM) and the COST Action 15137 ENRESSH (through a grant for a short-term scientific mission) to L.S