Biology subjects

Sarig, R.

Publications and source records attributed to Sarig, R..

3 recordsLinked to original sources

bioRxiv2025

3D-Printed Titanium Implants with Bioactive Peptide-polysaccharide Scaffolds for Personalized Bone Reconstruction

Large bone defects caused by trauma, tumor resection, or congenital abnormalities remain a major clinical challenge. Standard titanium implants are widely used due to their strength and biocompatibility, but their bioinert surfaces often lead to poor osseointegration. The emergence of 3D printing has enabled patient-specific titanium implants with tailored architecture and mechanical properties. However, these constructs still lack the bioactivity required for robust and spatially uniform bone integration, particularly within the implant core. To address this limitation, we developed a bioactive, cell-free strategy that integrates porous titanium implants with a nanofibrillar peptide-hyaluronic acid scaffold, delivered either as a hydrogel or in lyophilized form. The scaffold exhibited enhanced enzymatic stability and supported osteoblast-like cell adhesion in vitro. In a rabbit calvarial critical-size bone defect model, scaffold-integrated implants significantly outperformed inert controls, with hydrogel integration nearly doubling inner bone volume and improving trabecular architecture. Histological analysis confirmed enhanced bone-implant integration, active periosteum, healthy marrow, and reduced inflammation. This acellular, growth-factor-free approach combines the structural precision of titanium with the regenerative potential of ECM-mimicking scaffolds, offering a translatable pathway for personalized skeletal repair.

bioengineering↗

bioRxiv2023

Circuit to target approach defines an autocrine myofibroblast loop that drives cardiac fibrosis

Fibrosis is a broad pathology of excessive scarring with substantial medical implications. The fibrotic scar is produced by myofibroblasts that interact with macrophages. Fibrosis is a complex process involving thousands of factors, therefore, to better understand fibrosis and develop new therapeutic approaches, it is necessary to simplify and clarify the underlying concepts. Recently, we described a mathematical model for a macrophage-myofibroblast cell circuit, predicting two types of fibrosis - hot fibrosis with abundant macrophages and myofibroblasts, and cold fibrosis dominated by myofibroblasts alone. To test these concepts and intervention strategies in a medically relevant system, we use a widely studied in-vivo injury model for fibrosis, myocardial infarction (MI). We show that cold fibrosis is the final outcome of MI in both mice and pigs and demonstrate that fibrosis can shift toward healing in regenerative settings. MI begind with an increase of myofibroblasts and macrophages, followed by macrophage decline leading to persistent cold fibrosis (only myofibroblasts). During this process, fibroblasts, unlike macrophages, acquire distinct fate changes. Using mathematical modeling we predict that targeting of the autocrine signal for myofibroblast division could block cold fibrosis. We identify TIMP1 as an autocrine cardiac myofibroblast growth factor in-vitro. Treatment of adult mice after MI with anti-TIMP1 antibodies reduces fibrosis in-vivo. This study shows the utility of the concepts of hot and cold fibrosis and the feasibility of our circuit-to-target approach to reduce fibrosis after acute cardiac injury by inhibiting the myofibroblast autocrine loop.

systems biology↗

bioRxiv2022

The hidden secrets of the dental calculus: Calibration of a mass spectrometry protocol for dental calculus protein analysis

Dental calculus is a solid deposit that forms and accumulates on the tooth surface, entrapping oral microorganisms, biomolecules, and other micro-debris found in the oral cavity. Mass spectrometry analysis of its protein content opens a vista into the subjects diet, oral flora, and even some aspects of health, thus providing new insight and expanding our knowledge of archaic cultures. Multiple experimental protocols have been proposed for the optimal extraction of proteins from dental calculus. Herein, we compared various experimental conditions in order to calibrate and validate a protocol for protein extraction. Our results show that a high concentration of acetic acid followed by mechanical crushing and sonication provided the highest protein yield, while acetone precipitation enabled the identification of more distinct proteins. We validated this protocol using archeological samples, identifying human and microbial proteins in specimens from the 8th and 17th centuries (approximately 250-1300 years ago). These findings demonstrate that the developed protocol is useful for studying excavated archaeological samples and that it might be utilized to explore the biohistory, dietary habits, and microbiome of archaic populations.

molecular biology↗