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Biology subjects

Schaer, T.

Publications and source records attributed to Schaer, T..

3 recordsLinked to original sources

Absolute Quantification of Tissue Composition by Raman Spectroscopy

Raman spectroscopy captures the molecular fingerprints of living tissues without labels or tissue destruction. Translating these spectra into absolute measures of tissue biochemical composition remains a challenge owing to tissue-dependent optical properties, variations in sampling volume, and lack of normalization standards requisite for quantitative scaling. Here we introduce a scheme to derive the biochemical constituents of a tissue expressed as a percentage of the tissue wet weight, like biochemical assays, from Raman spectra measured optically. Nonlinear polynomial models of Raman spectra are trained on chemically defined phantoms that mimic the variability of the essential biochemical constituents of a tissue, accommodating spectral overlap and tissue-dependent optical effects. We validated this scheme using cartilage, a tissue fundamental to diarthrodial joint function. Cartilage is comprised of glycosaminoglycans, collagens and water that act synergistically to impart the rheological and tribological material properties essential to tissue function. Using biochemically perturbed live cartilage explants, phantom-calibrated Raman spectroscopy (PC-Raman) resolved constituent-specific changes and achieved quantitative agreement with independent biochemical assays (R-squared = 0.88-0.92; slopes {approx} 1.0; 95% confidence intervals {+/-}2.7-3.2%pt). We demonstrate that PC-Raman is applicable across the hierarchy of tissue interrogation from microscopic imaging of tissue extracellular matrix composition to macroscopic longitudinal monitoring of drug effects in-vitro using live tissue constructs and in-vivo assessments of cartilage regeneration in an equine cartilage repair model. Converting Raman spectra measurements of the essential biochemical constituents of a tissue in absolute terms (tissue wet-weight-%) allows for the non-destructive, longitudinal quantification of tissue composition in disease (tissue degeneration) and in response to treatment (tissue repair).

biochemistry↗

Relaxin-2 drives regenerative healing and suppresses scar formation

Fibrotic scarring is a pervasive and unresolved challenge in medicine, leading to permanent disfigurement, impaired mobility, and severe disruption of basic skin functions including elasticity, barrier protection, and thermoregulation. Despite its far-reaching personal, clinical, and economic impact, affecting hundreds of millions worldwide after surgery, trauma, and burns, no effective treatments exist to halt or reverse pathological scar formation. Scarring results from uncontrolled TGF-b1 signaling, which drives excessive deposition of extracellular matrix (ECM) proteins such as collagen-I/III and accumulation of alpha-smooth muscle actin (alpha-SMA), producing rigid, dysfunctional tissue. Here, we present a mechanistically guided approach targeting this unmet clinical need, leveraging the natural antifibrotic peptide hormone relaxin-2 (RLX-2) to actively remodel dermal architecture. RLX-2 signals via its G-protein coupled receptor RXFP1, upregulating matrix metalloproteinases (MMPs) and inhibiting aberrant ECM production. In TGF-b1-activated dermal fibroblasts across 2D and 3D in vitro models, ex vivo healthy and scarred human skin samples - cultured under physiological and pathological tension - and in an in vivo murine burn wound model, RLX-2 robustly suppresses fibrosis, restores regenerative tissue features, and rescues dermal architecture. Importantly, RLX-2 achieves this result without compromising the normal wound healing process, highlighting its potential as a transformative therapy for both prevention and reversal of pathological scarring.

bioengineering↗

Engineering a Biomimetic Multiphasic Suture Anchor System for Enhanced Rotator Cuff Enthesis Regeneration

Conventional suture anchor methods in rotator cuff repair often fail to replicate the native tendon-to-bone interface, leading to re-tears due to stress concentrations and poor biological integration at anchor sites. To address these challenges, we engineered a biomimetic multiphasic scaffold system (BMS) that integrates with standard suture anchors and deliver spatially organized structural and biological cues to enhance enthesis regeneration. The BMS comprises three distinct phases: aligned nanofibrous decellularized bovine Achilles tendon extracellular matrix (dECM) with stiff methacrylated hyaluronic acid (MeHA) for tendon regeneration; nonaligned nanofibrous dECM with soft MeHA for fibrocartilage formation; and a porous, citrate-based composite scaffold with bioactive glass for bone integration. In vitro, the BMS facilitated zone-specific tenogenic, fibrochondrogenic, and chondrogenic differentiation. Further, in vivo, it promoted successful integrative healing, forming distinct tendon, fibrocartilage, and bone regions at the repair site. This advanced multiphasic scaffold replicates native tissue properties, offering a promising strategy to improve rotator cuff repair. Its integration with conventional suture anchors provides an innovative design that enhances mechanical fixation and guides enthesis healing to reduce re-tear rates. Broadly, this platform offers a versatile solution for biointegrative repair strategies across complex soft-to-hard tissue interfaces.

bioengineering↗