Biology subjects

Fercher, D.

Publications and source records attributed to Fercher, D..

3 recordsLinked to original sources

bioRxiv2026

Vitamin C-Induced Photo-Redox Threshold Enables High-Fidelity Volumetric Printing of Pristine Collagen

Tomographic volumetric printing (TVP) enables rapid fabrication of complex, centimeter-scale 3D architectures. TVP of pristine proteins like collagen is attractive because it better preserves native bioactive motifs that regulate cell-matrix signaling. However, direct TVP of collagen remains challenging because dityrosine crosslinking, driven by visible-light-activated Ru(II)bpy32+/sodium persulfate (SPS), lacks an effective inhibitory mechanism. This results in near-immediate crosslinking upon exposure to light, which leads to an insufficient nonlinear threshold response that fails to suppress background curing. Here, we introduce vitamin C (L-ascorbic acid) as a biocompatible redox regulator to overcome this limitation. UV-Vis kinetics demonstrate that vitamin C suppresses Ru(III) accumulation and scavenges persulfate radicals within Ru/SPS system. This dual action generates a critical photo-redox and crosslinking threshold that inhibits dityrosine formation until vitamin C is depleted. Thereby the threshold response needed for TVP is successfully established, which enables high-fidelity volumetric printing of native collagen. Post-printing construct densification ([~]53% shrinkage) further improves feature resolution (80 {micro}m positive; 120 {micro}m negative) and yields mechanically stable and highly stretchable hydrogels (up to 180% strain). Collagen resin with vitamin C supports both cell seeding post-printing and cell-laden printing with high cell density and viability, enabling the rapid biofabrication of cell-instructive 3D microenvironments. Table of Contents (ToC) O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=37 SRC="FIGDIR/small/717972v1_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@742a83org.highwire.dtl.DTLVardef@930c06org.highwire.dtl.DTLVardef@1fa7f08org.highwire.dtl.DTLVardef@aa22bb_HPS_FORMAT_FIGEXP M_FIG C_FIG Tomographic volumetric printing (TVP) of native proteins is limited by uncontrolled background crosslinking. Here, vitamin C is introduced as a biocompatible redox-regulator to establish a tunable nonlinear polymerization threshold response for TVP. This strategy effectively suppresses background crosslinking and enables high-fidelity printing of pristine collagen. Subsequent post-print densification yields robust, elastic, and cell-compatible constructs with enhanced resolution for tissue engineering applications.

bioengineering↗

bioRxiv2025

Tissue Engineered Elastic Cartilage-Mimetic Auricular Grafts for Ear Reconstruction

Patients born with microtia, the congenital malformation of the external ear, face substantial psychosocial strain. Current reconstruction relies on harvesting rib cartilage, an invasive procedure associated with donor site morbidity and unnaturally stiff ears due to the use of hyaline cartilage. Tissue engineered auricles could overcome these drawbacks by providing patient-specific elastic cartilage without the need for rib harvest. Yet, key challenges such as fibrocartilage formation, inhomogeneous extracellular matrix formation and mechanical inferiority during ex vivo maturation remain, often leading to graft deformation and degradation in vivo. To address this gap, we integrated approaches maintaining the chondrogenic potential with growth factors, promoting elastic cartilage formation through stress-relaxing materials, and achieving homogeneous maturation by culturing grafts on an elevated bioreactor platform that enables uniform nutrient diffusion, using primary human auricular chondrocytes. Together these approaches resulted in the maturation of bioprinted auricular grafts that closely resemble native human auricular cartilage, demonstrated by the uniform distribution of elastin, glycosaminoglycans, and collagen II, and lack of collagen I. RNA sequencing revealed gene expression patterns consistent with the transition from fibrocartilage towards elastic cartilage. On a functional level, grafts achieved a compressive modulus of 1.1{+/-}0.03 MPa, matching that of native human auricular cartilage (1.0{+/-}0.1 MPa) and maintained their structural integrity for 6 weeks in a subcutaneous rat model, where they transitioned towards mature elastic fibers. These grafts represent the closest approximation of native elastic cartilage achieved ex vivo to date, bringing the field closer to a clinically viable, long-term therapy for children affected by microtia. One-sentence summaryBioprinted auricular grafts develop native-like elastic cartilage and advance towards a durable therapy for children with microtia.

bioengineering↗

bioRxiv2025

Leptin-Associated Sex Difference in TMJ OA Induced by Metabolic Endotoxemia

Background: Temporomandibular joint (TMJ) osteoarthritis (OA) is a degenerative disease affecting the whole synovial joint, with a higher prevalence in women. Obesity is recognised as a risk factor for knee OA, but its association with TMJ degeneration remains controversial. Lipopolysaccharide (LPS), or endotoxin, has increasingly been proposed as a mediator of obesity-related knee OA. In parallel, adipose-derived leptin played a role in the development of metabolic OA. This study investigated whether chronic LPS exposure induces TMJ OA and whether leptin is involved in this process. Methods: Six-month-old female and male Wistar rats received continuous subcutaneous LPS infusion to induce TMJ OA. At 10 weeks, peripheral blood, white adipose tissue, and TMJs were harvested for biochemical, histological, micro-computed tomography and gene expression analyses. Primary TMJ chondrocytes isolated from healthy rats were used to investigate sex-specific cellular responses to leptin and LPS in vitro. Results: Chronic LPS exposure induced mild, sex-divergent TMJ changes. Compared to same-sex healthy controls, LPS-treated females showed a marginally worse Mankin score (P = 0.053) with greater cartilage glycosaminoglycan loss (P = 0.032), synovitis and subchondral bone deterioration, whereas LPS-treated males only showed worse cartilage surface fibrillation. Both sexes showed subcutaneous adipocyte hypertrophy in response to LPS. Only females progressed to adipose inflammation and plasma leptin elevation (P = 0.018), which correlated strongly with total Mankin score (Spearman rho=+0.773, P = 0.024). Leptin was detected in the joint on chondrocytes co-expressing leptin receptor (OB-R) and inducible nitric oxide synthase (iNOS). The percentage of cells positive for leptin, OB-R and iNOS was differentially abundant in LPS-treated females than in sex-matched controls and LPS-treated males. In vitro, at the same leptin dose, female chondrocytes exhibited lower metabolic activity and greater oxidative stress than male chondrocytes. Notably, leptin upregulated matrix metallopeptidase (MMP)-13 expression only in LPS-primed female chondrocytes. Conclusion: Chronic systemic LPS exposure induced sex-divergent TMJ osteoarthritic pathology, adipose dysfunction and altered leptin signalling. The tissue-level changes were associated with leptin-linked inflammatory cascades amplified in female chondrocytes. These findings suggest that leptin is involved in the pathogenesis of systemic endotoxin-triggered TMJ OA and may partly explain sex differences in OA development.

pathology↗