Biology subjects

Sensini, A.

Publications and source records attributed to Sensini, A..

6 recordsLinked to original sources

bioRxiv2026

Highlighting strain rate dependent vibrational behavior of electrospun bundles for tendon/ligament and enthesis fascicle tissue regeneration

Enthesis tissue engineering aims to develop scaffolds that replicate the mechanical and structural gradients of the tendon/ligament-bone interface. Among the different biofabrication techniques, electrospinning is surely one of the most promising to fabricate morpho-mechanically relevant enthesis fascicle-inspired scaffolds. An interesting and totally unexplored characteristic of these nanofibrous scaffolds is their ability, when mechanically tested, to produce/transmit strain rate and nanofiber fracture-dependent mechanical vibrations, which can potentially influence surrounding tissues and cells. This study develops a method to investigate how scaffold geometry and material affect vibrational behavior under mechanical stimulation. Electrospun bundles of poly(L-lactic) acid/collagen type I (PLLA/Coll) were fabricated to mimic the fibrocartilage, the enthesis junction, and the tendon/ligament regions, while block copolymer poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT-PBT) bundles represented only the tendon/ligament. Scaffolds were morphologically and mechanically characterized, including strain rate-dependent vibrational response. Scanning electron microscopy confirmed distinct fiber architectures. Under monotonic tensile tests to failure, scaffolds exhibited strain rate-dependent mechanical behavior, with PLLA/Coll bundles showing dominant vibrational frequencies up to 4.2 {+/-} 0.9 Hz with a scaffolds geometry-dependent manner. PEOT-PBT scaffolds instead, displayed higher vibration attenuation, with dominant frequencies peaking at 0.539 {+/-} 0.063 Hz. They also showed lower tensile properties, reflecting a different mechanical and vibrational profile respect to PLLA/Coll bundles. Integrating vibrational characterization with mechanical testing offers a novel framework for designing scaffolds that more accurately reproduce the gradient mechanical environment of fibrous musculoskeletal tissues such as tendons/ligaments and their entheses. These findings highlight the potential of this combined approach to further increase the mechanical comprehension of electrospun scaffolds. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/699441v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1e4f38dorg.highwire.dtl.DTLVardef@31e658org.highwire.dtl.DTLVardef@9c590org.highwire.dtl.DTLVardef@18996e9_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Wave-inspired MEW scaffolds for enhanced ligament tissue regeneration

AO_SCPLOWBSTRACTC_SCPLOWLigament injuries remain a major clinical challenge due to the limited intrinsic healing capacity of these fibrous tissues. Here, we demonstrate the use of melt electrowriting (MEW) to fabricate poly({varepsilon}-caprolactone) (PCL) scaffolds with precisely engineered wave architectures that mimic the hierarchical organization and nonlinear mechanics of native ligaments. By tuning fiber geometry, we achieved scaffolds with distinct mechanical behaviors ranging from highly compliant to structurally resilient, enabling architecture-driven modulation of elastic modulus and fatigue response. Mechanical testing revealed that wave-patterned scaffolds dissipate energy efficiently and adapt structurally under cyclic loading, reproducing key features of ligament-like viscoelasticity. When cultured with human anterior cruciate ligament (ACL) cells, the scaffolds supported adhesion, proliferation, and spatially organized alignment, together with the expression of ligament-associated markers. The results demonstrate that MEW scaffolds provide a favorable environment for ligament cell adhesion and matrix synthesis, while highlighting the strong influence of geometry on cell organization and early matrix production. Overall, this study establishes wave-based MEW architectures as a versatile platform to guide ligament tissue formation.

bioengineering↗

bioRxiv2024

RELATIONSHIP BETWEEN ACTUAL STRESS AND IN SITU MORPHOLOGICAL CHANGES IN THE MECHANICAL BEHAVIOR OF BIOMIMETIC POROUS HIERARCHICAL SCAFFOLDS

This study investigates the evolution with strain of the material volume fraction (i.e., porosity) and geometry in porous scaffolds to obtain a more accurate description of their stress-strain behavior. Single bundles and hierarchical structures (8 bundles enveloped by a membrane) were produced by electrospinning as tendon/ligament scaffolds. They underwent a micro-tomography in situ tensile test. Apparent and net stress were obtained using the initial sample cross-section and material volume fraction to normalize axial force. Micro-tomography revealed sample morphology change with strain to calculate the actual stress-strain. Moreover, nanofibers arrangement was revealed by scanning electron microscopy on both bundles and membranes. The description of the mechanical response significantly changed using evolving morphometry (actual stress-strain) instead of initial static one (apparent stress-strain), for both single bundle and hierarchical structure. The actual elastic modulus of the single bundles (583{+/-}97 MPa) was statistically higher than that of the hierarchical structures (163{+/-}107 MPa). This is related to the membrane, membrane-bundle and inter-bundle interactions. In the hierarchical structure, portions of the material resisting traction are constituted by nanofibers not aligned with the load. The different definitions for the stress-strain behavior allow different accuracy levels depending on the experimental complexity. The evolution of morphology with deformation can significantly affect the description of the mechanical response of porous scaffolds. This has a double impact in practical applications: at the body scale, it allows a better comparison between the scaffold behavior and the target tissue; at the cellular scale, it predicts the actual substrate stiffness that cells will face. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/630537v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@5d5337org.highwire.dtl.DTLVardef@1027047org.highwire.dtl.DTLVardef@11966a9org.highwire.dtl.DTLVardef@a2e4e3_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Understanding the structure and mechanics of the sheep calcaneal enthesis: a relevant animal model for tissue engineering applications

Tendon/enthesis injuries are a worldwide clinical problem. Along the enthesis, collagen fibrils show a progressive loss of anisotropy and an increase in mineralization reaching the bone. This causes gradients of mechanical properties. The design of scaffolds to regenerate these load-bearing tissues requires of being validated in vivo in relevant large animal models. The sheep tendon of triceps surae muscle is an optimal animal model for this scope with limited knowledge about its structure and mechanics. We decided to understand in-depth its structure and full-field mechanics. Collagen fibrils morphology was investigated via scanning electron microscopy revealing a marked change in orientation/dimensions passing from tendon to enthesis. Backscatter electron images and nanoindentation at the enthesis/bone marked small gradients of mineralization at the mineralized fibrocartilage reaching 27%wt and indentation modulus around 17-30 GPa. The trabecular bone instead had indentation modulus around 15-22 GPa. Mechanical tensile tests with digital image correlation confirmed the typical non-linear behavior of tendons (failure strain = 8.2{+/-}1.0%; failure force = 1369{+/-}187 N) with maximum principal strains reaching mean values of {varepsilon}p1[~]7%. The typical auxetic behavior of tendon was highlighted by the minimum principal strains ({varepsilon}p2[~]5%), progressively dampened at the enthesis. Histology revealed that this behavior was caused by a local thickening of the epitenon. Cyclic tests showed a force loss of 21{+/-}7 % at the last cycle. These findings will be fundamental for biofabrication and clinicians interested in designing the new generation of scaffolds for enthesis regeneration. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/630234v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@143f0a8org.highwire.dtl.DTLVardef@16cb394org.highwire.dtl.DTLVardef@181be61org.highwire.dtl.DTLVardef@f9f2d9_HPS_FORMAT_FIGEXP M_FIG C_FIG Statement of SignificanceTendon and enthesis lesions are a clinical problem. To validate scaffolds for these applications large animal models are needed. Sheep tendon of triceps surae muscle is an optimal site for this scope. However, little is known about its extracellular matrix structure and mechanical properties. This work investigates the structure and mechanics of this tissue from different points of view. Scanning electron microscopy and histology studied its extracellular matrix morphology and composition. Backscattered electron images and nanoindentation assessed gradients of mineralization and stiffness at the enthesis. Mechanical tensile and cyclic tests coupled with digital image correlation elucidated its mechanics and superficial strain distribution. These findings will be fundamental for biofabrication and clinician experts to design innovative scaffolds to regenerate the enthesis.

bioengineering↗

bioRxiv2024

Revealing the Auxetic Behavior of Biomimetic Multi-material and Region-specific Nanofibrous Scaffolds via Synchrotron Multiscale Digital Volume Correlation: Innovative Building Blocks for the Enthesis Regeneration

Enthesis lesions are one of the prevalent causes of injuries in the tendon tissue. The gradient of mineralization, extracellular matrix organization and auxetic mechanical properties, make enthesis regeneration challenging. Innovative electrospun fascicle-inspired nanofibrous poly(L-lactic)acid/collagen type I blend scaffolds were developed. Specifically, a mineralized fibrocartilage-inspired region (with/without nano-mineralization with hydroxyapatite), where random and aligned nanofibers coexist, is connected to a tendon-like region made of aligned nanofibers, through a conical non-mineralized fibrocartilage-inspired junction. Scanning electron microscopy and synchrotron nano-tomography show the morphological biomimicry of scaffolds with the natural tendon fascicles. Human mesenchymal stromal cells spheroids cultures confirm a balanced expression of both tendon, cartilage and bone markers on the non-mineralized scaffolds compared with the mineralized ones. Mechanical tests, at different physiological strain-rates, reveal a biomimetic mechanical behavior of scaffolds and the ability of junctions to tune the mechanics of their surrounding sites. Multiscale synchrotron in situ tensile tests, coupled with Digital Volume Correlation, elucidate the full-field strain distribution of scaffolds from the structural down to the nanofiber level, highlighting the auxetic mechanical behavior of junctions typical of the natural enthesis. The findings and cutting-edge investigations of our study suggest the suitability of these enthesis-inspired fascicles as innovative scaffolds for enhanced enthesis regeneration.

bioengineering↗

bioRxiv2023

Full-field strain distribution in hierarchical electrospun nanofibrous Poly-L(lactic) acid and Collagen based scaffolds for tendon and ligament tissue regeneration: a multiscale study

Regeneration of injured tendons and ligaments (T/L) is a worldwide need. In this study electrospun hierarchical scaffolds made of a poly (L-lactic) acid and collagen blend were developed reproducing all the multiscale levels of aggregation of these tissues. Scanning electron microscopy, microCT and tensile mechanical tests were carried out, including a multiscale digital volume correlation analysis to measure the full-field strain distribution of electrospun structures. The principal tensile and compressive strains detected the pattern of strains caused by the nanofibers rearrangement, while the deviatoric strains revealed the related internal sliding of nanofibers and bundles. The results of this study confirmed the biomimicry of such electrospun hierarchical scaffolds, paving the way to further tissue engineering and clinical applications. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/543145v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1a67baorg.highwire.dtl.DTLVardef@190149aorg.highwire.dtl.DTLVardef@38968borg.highwire.dtl.DTLVardef@123bb49_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗