Evolving an improved axial structure for fibrillar collagen

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Tendon tissue engineering : An overview of biologics to promote tendon healing and repair

Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors acknowledge operating grant support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 955685, www.helsinki.fi/p4fit .Peer reviewedPublisher PD

Mechanics-driven mechanobiological mechanisms of arterial tortuosity

[EN] Arterial tortuosity manifests in many conditions, including hypertension, genetic mutations predisposing to thoracic aortopathy, and vascular aging. Despite evidence that tortuosity disrupts efficient blood flow and that it may be an important clinical biomarker, underlying mechanisms remain poorly understood but are widely appreciated to be largely biomechanical. Many previous studies suggested that tortuosity may arise via an elastic structural buckling instability, but the novel experimental-computational approach used here suggests that tortuosity arises from mechanosensitive, cell-mediated responses to local aberrations in the microstructural integrity of the arterial wall. In particular, computations informed by multimodality imaging show that aberrations in elastic fiber integrity, collagen alignment, and collagen turnover can lead to a progressive loss of structural stability that entrenches during the development of tortuosity. Interpreted in this way, microstructural defects or irregularities of the arterial wall initiate the condition and hypertension is a confounding factor.This work was supported by grants from the U.S. NIH (R01 HL105297, P01 HL134605, and U01 HL142518)Weiss, D.; Cavinato, C.; Gray, A.; Ramachandra, AB.; Avril, S.; Humphrey, JD.; Latorre, M. (2020). Mechanics-driven mechanobiological mechanisms of arterial tortuosity. Science Advances. 6(49):1-26. https://doi.org/10.1126/sciadv.abd357412664

The genetics and disease mechanisms of rhegmatogenous retinal detachment

Rhegmatogenous retinal detachment (RRD) is a sight threatening condition that warrants immediate surgical intervention. To date, 29 genes have been associated with monogenic disorders involving RRD. In addition, RRD can occur as a multifactorial disease through a combined effect of multiple genetic variants and non-genetic risk factors. In this review, we provide a comprehensive overview of the spectrum of hereditary disorders involving RRD. We discuss genotype-phenotype correlations of these monogenic disorders, and describe genetic variants associated with RRD through multifactorial inheritance. Furthermore, we evaluate our current understanding of the molecular disease mechanisms of RRD-associated genetic variants on collagen proteins, proteoglycan versican, and the TGF-β pathway. Finally, we review the role of genetics in patient management and prevention of RRD. We provide recommendations for genetic testing and prophylaxis of at-risk patients, and hypothesize on novel therapeutic approaches beyond surgical intervention.</p

Simulation of Subject-Specific Progression of Knee Osteoarthritis and Comparison to Experimental Follow-up Data : Data from the Osteoarthritis Initiative

Economic costs of osteoarthritis (OA) are considerable. However, there are no clinical tools to predict the progression of OA or guide patients to a correct treatment for preventing OA. We tested the ability of our cartilage degeneration algorithm to predict the subject-specific development of OA and separate groups with different OA levels. The algorithm was able to predict OA progression similarly with the experimental follow-up data and separate subjects with radiographical OA (Kellgren-Lawrence (KL) grade 2 and 3) from healthy subjects (KL0). Maximum degeneration and degenerated volumes within cartilage were significantly higher (p <0.05) in OA compared to healthy subjects, KL3 group showing the highest degeneration values. Presented algorithm shows a great potential to predict subjectspecific progression of knee OA and has a clinical potential by simulating the effect of interventions on the progression of OA, thus helping decision making in an attempt to delay or prevent further OA symptoms.Peer reviewe

The genetics and disease mechanisms of rhegmatogenous retinal detachment

Rhegmatogenous retinal detachment (RRD) is a sight threatening condition that warrants immediate surgical intervention. To date, 29 genes have been associated with monogenic disorders involving RRD. In addition, RRD can occur as a multifactorial disease through a combined effect of multiple genetic variants and non-genetic risk factors. In this review, we provide a comprehensive overview of the spectrum of hereditary disorders involving RRD. We discuss genotype-phenotype correlations of these monogenic disorders, and describe genetic variants associated with RRD through multifactorial inheritance. Furthermore, we evaluate our current understanding of the molecular disease mechanisms of RRD-associated genetic variants on collagen proteins, proteoglycan versican, and the TGF-β pathway. Finally, we review the role of genetics in patient management and prevention of RRD. We provide recommendations for genetic testing and prophylaxis of at-risk patients, and hypothesize on novel therapeutic approaches beyond surgical intervention.</p

From Transcript to Tissue: Multiscale Modeling from Cell Signaling to Matrix Remodeling

[EN] Tissue-level biomechanical properties and function derive from underlying cell signaling, which regulates mass deposition, organization, and removal. Here, we couple two existing modeling frameworks to capture associated multiscale interactions¿one for vessel-level growth and remodeling and one for cell-level signaling¿and illustrate utility by simulating aortic remodeling. At the vessel level, we employ a constrained mixture model describing turnover of individual wall constituents (elastin, intramural cells, and collagen), which has proven useful in predicting diverse adaptations as well as disease progression using phenomenological constitutive relations. Nevertheless, we now seek an improved mechanistic understanding of these processes; we replace phenomenological relations in the mixture model with a logic-based signaling model, which yields a system of ordinary differential equations predicting changes in collagen synthesis, matrix metalloproteinases, and cell proliferation in response to altered intramural stress, wall shear stress, and exogenous angiotensin II. This coupled approach promises improved understanding of the role of cell signaling in achieving tissue homeostasis and allows us to model feedback between vessel mechanics and cell signaling. We verify our model predictions against data from the hypertensive murine infrarenal abdominal aorta as well as results from validated phenomenological models, and consider effects of noisy signaling and heterogeneous cell populations.This work was supported by Grants from the US NIH (R01 HL105297, P01 HL134605, R01 HL139796, U01 HL142518, R01 HL146723)Irons, L.; Latorre, M.; Humphrey, JD. (2021). From Transcript to Tissue: Multiscale Modeling from Cell Signaling to Matrix Remodeling. Annals of Biomedical Engineering. 48(7):1701-1715. https://doi.org/10.1007/s10439-020-02713-81701171548