Biology subjects

Gelmi, A.

Publications and source records attributed to Gelmi, A..

3 recordsLinked to original sources

bioRxiv2026

Changing the Fate of Dystrophin-Deficient Myoblasts via Hetero ligand Nanoclusters on Biomaterial Surface: Effects of Integrin-Syndecan or Dystroglycan Crosstalk

Engineering skeletal muscle tissue regeneration, particularly in dystrophin-deficient muscles is dependent on facilitating myogenesis and recovery of myotube structure and function, which can be challenging due to compromised cell-extracellular matrix (ECM) interactions. The current study explored the potential impact of enhancing dystrophin-associated protein complex and focal adhesion formation and the interaction with associated target receptors to improve cellular response in both normal and Duchenne muscular dystrophy (Dmd) mutant myoblasts. This was achieved by multivalent dual ligands functionalization of RAFT-synthesized copolymer with fibronectin- and laminin-derived adhesion peptides (RGD, AG73, and A2G80) and their clustering at the biointerface. Our findings demonstrated the synergistic effect of integrin-syndecan/dystroglycan engagement and their clustering on enhancing myoblast adhesion, proliferation, and differentiation, partially overcoming the deficits caused by loss of dystrophin. Furthermore, enhanced focal adhesion formation and elevated receptor localization, particularly dystroglycan, at the sarcolemma were associated with improved structural organization, mechanical stability, and neuromuscular connectivity of myotubes. These results suggest a novel insight into harnessing next-generation molecularly engineered biomaterials with robust interaction with cells mechanosensors for advancing skeletal muscle tissue engineering, offering potential applications in the regeneration of dystrophic muscle and the development of neuromuscular disease models for drug testing. O_FIG O_LINKSMALLFIG WIDTH=174 HEIGHT=200 SRC="FIGDIR/small/717576v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@16c6b87org.highwire.dtl.DTLVardef@107a84borg.highwire.dtl.DTLVardef@1b9e4ddorg.highwire.dtl.DTLVardef@160a9a7_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract/ToCC_FLOATNO Current work developed molecularly engineered biomaterial surfaces with nanoscale clustering of integrin-, syndecan-, and/or dystroglycan-binding peptides for skeletal muscle tissue regeneration. By controlling peptide distribution and type at the biointerface, cell adhesion, proliferation, and differentiation were modulated in dystrophin-deficient myoblasts. Accordingly, the results demonstrated significant improvement in myotube structural organization, mechanical stiffness, and their innervation in response to heteronanoclusters. C_FIG

bioengineering↗

bioRxiv2024

Real-time Biomechanical Characterisation of Cytoskeletal Remodelling

As progenitors for tissue, human mesenchymal stem cells (hMSCs) with ability of self-proliferation and differentiation into various cell types such as osteocytes and adipocytes show great potential applications for tissue engineering. Stem cell fate regulation is highly affected by the cytoskeleton structure and mechanical properties. In this paper, quantitative Atomic Force Microscopy (Q-AFM) was used to continuously characterise topography and biomechanical properties while applying cytoskeleton disruptors to hMSCs. The cell stiffness (quantified by Youngs modulus), primarily governed by the cytoskeleton network, had quantifiable changes associated with cytoskeleton polymerisation and depolymerisation when treatments were applied. Furthermore, with Q-AFM measurements, these changes were tracked in real time over a period of minutes to hours, and the biomechanical properties of the cells were tracked through the applied treatment and subsequent recovery post treatment. Here we present the capability of Q-AFM to perform real time biomechanical characterisation of living cells, directly correlated to intracellular structure and cytoskeletal remodelling.

biophysics↗

bioRxiv2020

Driving Hierarchical Collagen Fiber Formation for Functional Tendon, Ligament, and Meniscus Replacement

Hierarchical collagen fibers are the primary source of strength in musculoskeletal tendons, ligaments, and menisci. It has remained a challenge to develop these large fibers in engineered replacements or in vivo after injury. The objective of this study was to investigate the ability of restrained cell-seeded high density collagen gels to drive hierarchical fiber formation for multiple musculoskeletal tissues. We found boundary conditions applied to high density collagen gels were capable of driving tenocytes, ligament fibroblasts, and meniscal fibrochondrocytes to develop native-sized hierarchical collagen fibers 20-40 {micro}m in diameter. The collagen fibers organize similar to native collagen with native fibril banding patterns and hierarchical fiber bundles 50-350 {micro}m in diameter by 6 weeks. Mirroring fiber organization, tensile properties of restrained samples improved significantly with time, reaching [~]1 MPa. Additionally, tendon, ligament, and meniscal cells produced significantly different sized fibers, different degrees of crimp, and different GAG concentrations, which corresponded with respective native tissue. To our knowledge, these are some of the largest, most organized fibers produced to date in vitro. Further, cells produced tissue specific hierarchical fibers, suggesting this system is a promising tool to better understand cellular regulation of fiber formation to better stimulate it in vivo after injury.

bioengineering↗