The importance of 3D fibre architecture in cancer and implications for biomaterial model design

Ashworth, Jennifer C.; Cox, Thomas R.

doi:10.1038/s41568-024-00704-8

Cited by 4 publications

References 258 publications

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Quantitative Assessment of Collagen Architecture to Determine Role of Tumor Stroma During Vestibular Schwannoma Progression

Fisher,

Duhon,

Nguyen

et al. 2024

Otolaryngol.--head neck surg.

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ObjectiveThe primary objective was to characterize the abundance and architecture of collagen in the extracellular matrix in vestibular schwannoma (VS). The secondary objective was to investigate the association between collagen architecture and tumor size.Study DesignRetrospective cohort study.SettingAcademic referral center.MethodsTumor samples were obtained from patients with sporadic VS undergoing microsurgical resection. Histological analyses were performed including picrosirius red (PSR) staining under polarized light. Collagen architecture was quantified using an automated fiber detection software. Second Harmonic Generation (SHG) microscopy and immunofluorescence (IF) were utilized to characterize collagen architecture.ResultsEleven tumor specimens were included (mean tumor diameter = 2.80 cm, range 1.5‐4.0 cm), and were divided into large (mean diameter = 3.5 ± 0.4 cm) and small (mean tumor diameter = 2.0 ± 0.4 cm) cohorts based on size. The large VS cohort showed significantly higher collagen density (27.65% vs 12.73%, P = .0043), with more thick fibers (mature Type I, 24.54% vs 12.97%, P = .0022) and thin fibers (immature Type I or mature Type III, 23.55% vs 12.27%, P = .026). Tumor volume correlated with greater degree of collagen fiber disorganization (P = .0413, r2 = 0.298). Specifically, collagen type I intensity was significantly higher in large VS compared to small tumors (P < .001) and peripheral nerve (P = .028).ConclusionLarger VS exhibit increased collagen abundance in the tumor stroma, and a more disorganized collagen architecture compared to smaller VS and normal peripheral nerve tissue. This finding indicates that collagen organization may play a significant role in extracellular matrix remodeling and the progression of VS.

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Quantitative Assessment of Collagen Architecture to Determine Role of Tumor Stroma During Vestibular Schwannoma Progression

Fisher,

Duhon,

Nguyen

et al. 2024

Otolaryngol.--head neck surg.

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Modeling collagen fibril degradation as a function of matrix microarchitecture

Debnath,

Narasimhan,

Fraley

et al. 2024

Soft Matter

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Modeling collagen fibril degradation as a function of matrix microarchitecture

Debnath,

Narasimhan,

Fraley

et al. 2024

Preprint

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Collagenolytic degradation is a process fundamental to tissue remodeling. The microarchitecture of collagen fibril networks changes during development, aging, and disease. Such changes to microarchitecture are often accompanied by changes in matrix degradability.In vitro, collagen matrices of the same concentration but different microarchitectures also vary in degradation rate. How do different microarchitectures affect matrix degradation? To answer this question, we developed a computational model of collagen degradation. We first developed a lattice model that describes collagen degradation at the scale of a single fibril. We then extended this model to investigate the role of microarchitecture using Brownian dynamics simulation of enzymes in a multi-fibril three dimensional matrix to predict its degradability. Our simulations predict that the distribution of enzymes around the fibrils is non-uniform and depends on the microarchitecture of the matrix. This non-uniformity in enzyme distribution can lead to different extents of degradability for matrices of different microarchitectures. Our model predictions were tested usingin vitroexperiments with synthesized collagen gels of different microarchitectures. Experiments showed that indeed degradation of collagen depends on the matrix architecture and fibril thickness. In summary, our study shows that the microarchitecture of the collagen matrix is an important determinant of its degradability.

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The importance of 3D fibre architecture in cancer and implications for biomaterial model design

Cited by 4 publications

References 258 publications

Quantitative Assessment of Collagen Architecture to Determine Role of Tumor Stroma During Vestibular Schwannoma Progression

Quantitative Assessment of Collagen Architecture to Determine Role of Tumor Stroma During Vestibular Schwannoma Progression

Modeling collagen fibril degradation as a function of matrix microarchitecture

Modeling collagen fibril degradation as a function of matrix microarchitecture

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