Biology subjects

El Haj, A. J.

Publications and source records attributed to El Haj, A. J..

4 recordsLinked to original sources

bioRxiv2024

Localized Delivery of Growth Factors from Microparticles Modulate Osteogenic and Chondrogenic Gene Expression in Growth Factor-dependent Manner in an ex vivo Chick Embryonic Bone Model.

AbstractGrowth factors play a crucial role in regulating various cellular functions, including proliferation and differentiation. Consequently, the biomaterial-based delivery of exogenous growth factors presents a promising strategy in regenerative medicine to manage the healing process and restore tissue function. For effective therapeutic applications, it is essential that these active compounds are precisely targeted to the site of regeneration, with release kinetics that align with the slow pace of tissue growth. We have developed an ex vivo model utilizing a developing embryonic chick bone, and using PLGA based microparticles as controlled-release systems, allowing for the investigation of spatiotemporal effects of growth factor delivery on cell differentiation and tissue formation. Our findings demonstrate that BMP2 and FGF2 can significantly alter cell morphology and zonally pattern collagen deposition within the model, but only when the growth factor presentation rate is carefully regulated. Furthermore, the growth factor-dependent responses observed underscore the potential of this model to explore the interactions between cells and the growth factors released from biomaterials in an approach which can be applied for bone tissue engineering.

bioengineering↗

bioRxiv2024

Sweet and sticky: increased cell adhesion through click-mediated functionalization of regenerative liver progenitor cells

The burgeoning field of cell therapies is rapidly expanding, offering the promise to tackle complex and unsolved healthcare problems. One prominent example is represented by CAR T-cells, which have been introduced into the clinic for treating a variety of cancers. Promising cell-based candidates have also been developed to promote tissue regeneration, showing high potencies for the treatment of damaged liver. Nevertheless, in the remit of regenerative medicine, cell-therapy efficacies remain suboptimal as a consequence of the low engraftment of injected cells to the existing surrounding tissue. Herein, we present a facile approach to enhance the adhesion and engraftment of therapeutic hepatic progenitor cells (HPCs) through specific and homogeneous cell surface modification with exogenous polysaccharides, without requiring genetic modification. Coated HPCs exhibited significantly increased markers of adhesion and cell spreading, demonstrating preferential interactions with certain extra-cellular matrix proteins. Moreover, they displayed enhanced binding to endothelial cells and 3D liver microtissues. This translatable methodology shows promise for improving therapeutic cell engraftment, offering a potential alternative to liver transplantation in end-stage liver disease.

bioengineering↗

bioRxiv2021

Remote spatially variant debiased profiling of cell and tissue mechanical properties

The role of the mechanical environment in defining tissue function, development and growth has been shown to be fundamental. Assessment of the changes in stiffness of tissue matrices at multiple scales has relied mostly on invasive and often specialist equipment such as AFM or mechanical testing devices poorly suited to the cell culture workflow.In this paper, we have developed a novel unbiased passive optical coherence elastography method, exploiting ambient vibrations in the sample that enables real-time noninvasive quantitative profiling of cells and tissues. We demonstrate a robust method that decouples optical scattering and mechanical properties by actively compensating for scattering associated noise bias and reducing variance. The efficiency for the method to retrieve ground truth is validated in silico and in vitro, and exemplified for key applications such as time course mechanical profiling of bone and cartilage spheroids, tissue engineering cancer models, tissue repair models and single cell. Our method is readily implementable with any commercial optical coherence tomography system without any hardware modifications, and thus offers a breakthrough in tissue mechanical assessment for novel on line assessment of spatial mechanical properties for organoids, soft tissues and tissue engineering.

bioengineering↗

bioRxiv2020

Experimental and mathematical modelling of magnetically labelled mesenchymal stromal cell delivery

A key challenge for stem cell therapies is the delivery of therapeutic cells to the repair site. Magnetic targeting has been proposed as a platform for defining clinical sites of delivery more effectively. In this paper we use a combined in vitro experimental and mathematical modelling approach to explore the magnetic targeting of mesenchymal stromal cells (MSCs) labelled with magnetic nanoparticles using an external magnet. This study aims to (i) demonstrate the potential of magnetic tagging for MSC delivery, (ii) examine the effect of red blood cells (RBCs) on MSC capture efficacy and (iii) highlight how mathematical models can provide both insight into mechanics of therapy and predictions about cell targeting in vivo. In vitro MSCs are cultured with magnetic nanoparticles and circulated with RBCs over an external magnet. Cell capture efficacy is measured for varying magnetic field strengths and RBC percentages. We use a 2D continuum mathematical model to represent the flow of magnetically tagged MSCs with RBCs. Numerical simulations demonstrate qualitative agreement with experimental results showing better capture with stronger magnetic fields and lower levels of RBCs. We additionally exploit the mathematical model to make hypotheses about the role of extravasation and identify future in vitro experiments to quantify this effect.

bioengineering↗