Biology subjects

Kanczler, J.

Publications and source records attributed to Kanczler, J..

4 recordsLinked to original sources

bioRxiv2026

Decoupled ionic and particulate clearance pathways determine the in vivo fate of a synthetic nanoclay-BMP-2 biomaterial during ectopic bone induction.

Nanoclay-based biomaterials offer promise for localised growth factor presentation, yet their in vivo degradation, clearance, and systemic fate remain poorly defined. Here, we investigate the fate of a synthetic nanoclay-BMP-2 gel during ectopic bone induction using a combination of in vivo imaging, histology, and component-resolved elemental analysis. Fluorescent tracking confirmed prolonged localisation of BMP-2 within the nanoclay gel and robust bone induction despite negligible growth-factor release. Inductively coupled plasma mass spectrometry (ICP-MS) revealed divergent clearance kinetics for lithium and silicon, structurally distinct components of the clay crystalline lattice, indicating decoupled ionic and particulate degradation pathways. Early clearance was dominated by cell-mediated fragmentation and the transport of clay particulates, while later stages involved preferential lithium release associated with local clay dissolution as well as integration within newly formed bone. Systemic biodistribution analysis demonstrated rapid, transient lithium release into circulation with renal clearance, contrasted with initial hepatic and then later-phase renal handling of silicon species. Together, these findings define a multiphasic in vivo clearance model for nanoclay biomaterials consistent with progressive remodelling, localised BMP-2 activity and, importantly, safe systemic handling. This work provides mechanistic insight into the activity and clearance of nanoclay-based regenerative therapies and establishes the importance of component-resolved tracking for evaluating the biodistribution of degradable inorganic biomaterials.

bioengineering↗

bioRxiv2026

The material properties of the cell determine microbubble-induced cell deformation and permeabilisation

Mechanical properties influence how cells withstand and transmit force, but their role in clinically relevant, high-frequency therapeutic perturbations remains poorly understood. Ultrasound-stimulated microbubbles can locally deform cells and tissues to enhance drug delivery, yet therapeutic responses vary markedly across mechanical microenvironments. How cellular material properties govern microbubble-cell interactions at megahertz loading rates - well beyond the range accessible to conventional mechanobiology - remains unresolved. Here we combine ultra-high-speed imaging with digital image correlation to map microbubble-induced deformation in living cells at ultrasound frequencies. We show that oscillating microbubbles generate harmonic deformation waves whose spatial decay defines a micrometre-scale attenuation length governed by cytoskeletal organisation and intracellular viscoelastic dissipation. Pharmacological softening or stiffening alters both deformation propagation and wave speed, and these mechanical changes predict permeabilisation efficiency in tumour-derived and primary human bone-marrow stromal cells. These findings establish cellular viscoelasticity as a determinant of microbubble bioeffects and suggest that tissue mechanical state can be used as a design parameter for ultrasound-mediated therapeutic delivery.

bioengineering↗

bioRxiv2026

Repetition-controllable gain-managed nonlinear fiber amplifier enables ultrashort, multiphoton imaging with reduced photodamage

1.We report a repetition-controllable gain-managed nonlinear fiber amplifier (GMNA) that delivers near-infrared 50-fs pulses with pulse energies up to 150 nJ and a widely tunable repetition rate from 1-20 MHz, while maintaining stable pulse quality across the full range. Using this source, we demonstrate label-free multiphoton imaging--including metabolic autofluorescence (2PF/3PF), second/third-harmonic generation, and Simultaneous Label-free Autofluorescence Multiharmonic (SLAM) microscopy imaging--across live cells, human lung spheroids, and hard tissues. We further assess the impact of laser repetition rate on photodamage at fixed pulse energy, supported by preliminary measurements indicating lower damage at lower repetition rate. Collectively, the compact architecture and repetition-rate agility of the GMNA enable real-time optimization of imaging speed, depth, and sample safety for advanced biological microscopy.

biophysics↗

bioRxiv2022

Nonlinear micro finite element models based on digital volume correlation measurements predict early microdamage in newly formed bone

Bone regeneration in critical-sized defects is a clinical challenge, with biomaterials under constant development aiming at enhancing the natural bone healing process. The delivery of bone morphogenetic proteins (BMPs) in appropriate carriers represents a promising strategy for bone defect treatment but optimisation of the spatial-temporal release is still needed for the regeneration of bone with biological, structural, and mechanical properties comparable to the native tissue. Nonlinear micro finite element (FE) models can address some of these challenges by providing a tool able to predict the biomechanical strength and microdamage onset in newly formed bone when subjected to physiological or supraphysiological loads. Yet, these models need to be validated against experimental data. In this study, experimental local displacements in newly formed bone induced by osteoinductive biomaterials subjected to in situ X-ray computed tomography compression in the apparent elastic regime and measured using digital volume correlation (DVC) were used to validate FE models. Displacement predictions from homogeneous linear FE models were highly correlated to DVC-measured local displacements, while tissue heterogeneity capturing mineralisation differences showed negligible effects. Nonlinear FE models improved the correlation and showed that tissue microdamage occurs at low apparent strains. Microdamage seemed to occur next to large cavities or in biomaterial-induced thin trabeculae, independent of the mineralisation. While localisation of plastic strain accumulation was similar, the amount of damage accumulated in these locations was slightly higher when including material heterogeneity. These results demonstrate the ability of the nonlinear FE model to capture local microdamage in newly formed bone tissue and can be exploited to improve the current understanding of healing bone and mechanical competence. This will ultimately aid the development of BMPs delivery systems for bone defect treatment able to regenerate bone with optimal biological, mechanical, and structural properties.

bioengineering↗