El-Rashidy, A. A., I. A. Radwan, D. Rady, S. El Moshy, M. M. S. Abbass, K. M. Sadek, A. E. El-Arab, and K. F. M. El-Sayed, "Dental Mesenchymal Stem/Progenitor Cells: A New Prospect in Regenerative Medicine", Stem Cells : Springer Cham, 2021.
El-Rashidy, A. A., S. El Moshy, I. A. Radwan, D. Rady, M. M. S. Abbass, C. E. Dörfer, and K. M Fawzy El-Sayed, "Effect of Polymeric Matrix Stiffness on Osteogenic Differentiation of Mesenchymal Stem/Progenitor Cells: Concise Review.", Polymers, vol. 13, issue 17, 2021. Abstract

Mesenchymal stem/progenitor cells (MSCs) have a multi-differentiation potential into specialized cell types, with remarkable regenerative and therapeutic results. Several factors could trigger the differentiation of MSCs into specific lineages, among them the biophysical and chemical characteristics of the extracellular matrix (ECM), including its stiffness, composition, topography, and mechanical properties. MSCs can sense and assess the stiffness of extracellular substrates through the process of mechanotransduction. Through this process, the extracellular matrix can govern and direct MSCs' lineage commitment through complex intracellular pathways. Hence, various biomimetic natural and synthetic polymeric matrices of tunable stiffness were developed and further investigated to mimic the MSCs' native tissues. Customizing scaffold materials to mimic cells' natural environment is of utmost importance during the process of tissue engineering. This review aims to highlight the regulatory role of matrix stiffness in directing the osteogenic differentiation of MSCs, addressing how MSCs sense and respond to their ECM, in addition to listing different polymeric biomaterials and methods used to alter their stiffness to dictate MSCs' differentiation towards the osteogenic lineage.

Abbass, M. M. S., A. A. El-Rashidy, K. M. Sadek, S. El Moshy, I. A. Radwan, D. Rady, C. E. Dörfer, and K. M Fawzy El-Sayed, "Hydrogels and Dentin-Pulp Complex Regeneration: From the Benchtop to Clinical Translation.", Polymers, vol. 12, issue 12, 2020. Abstracthydrogels_and_dentin-pulp_complex_regeneration_from_the_benchtop_to_clinical_translation.pdf

Dentin-pulp complex is a term which refers to the dental pulp (DP) surrounded by dentin along its peripheries. Dentin and dental pulp are highly specialized tissues, which can be affected by various insults, primarily by dental caries. Regeneration of the dentin-pulp complex is of paramount importance to regain tooth vitality. The regenerative endodontic procedure (REP) is a relatively current approach, which aims to regenerate the dentin-pulp complex through stimulating the differentiation of resident or transplanted stem/progenitor cells. Hydrogel-based scaffolds are a unique category of three dimensional polymeric networks with high water content. They are hydrophilic, biocompatible, with tunable degradation patterns and mechanical properties, in addition to the ability to be loaded with various bioactive molecules. Furthermore, hydrogels have a considerable degree of flexibility and elasticity, mimicking the cell extracellular matrix (ECM), particularly that of the DP. The current review presents how for dentin-pulp complex regeneration, the application of injectable hydrogels combined with stem/progenitor cells could represent a promising approach. According to the source of the polymeric chain forming the hydrogel, they can be classified into natural, synthetic or hybrid hydrogels, combining natural and synthetic ones. Natural polymers are bioactive, highly biocompatible, and biodegradable by naturally occurring enzymes or via hydrolysis. On the other hand, synthetic polymers offer tunable mechanical properties, thermostability and durability as compared to natural hydrogels. Hybrid hydrogels combine the benefits of synthetic and natural polymers. Hydrogels can be biofunctionalized with cell-binding sequences as arginine-glycine-aspartic acid (RGD), can be used for local delivery of bioactive molecules and cellularized with stem cells for dentin-pulp regeneration. Formulating a hydrogel scaffold material fulfilling the required criteria in regenerative endodontics is still an area of active research, which shows promising potential for replacing conventional endodontic treatments in the near future.

Rady, D., M. M. S. Abbass, A. A. El-Rashidy, S. El Moshy, I. A. Radwan, C. E. Dörfer, and K. M Fawzy El-Sayed, "Mesenchymal Stem/Progenitor Cells: The Prospect of Human Clinical Translation", Stem Cells International, vol. 2020: Hindawi, pp. 8837654, 2020. Abstractmesenchymal_stem-progenitor_cells_the_prospect_of_human_clinical_translation.pdfWebsite

Mesenchymal stem/progenitor cells (MSCs) are key players in regenerative medicine, relying principally on their differentiation/regeneration potential, immunomodulatory properties, paracrine effects, and potent homing ability with minimal if any ethical concerns. Even though multiple preclinical and clinical studies have demonstrated remarkable properties for MSCs, the clinical applicability of MSC-based therapies is still questionable. Several challenges exist that critically hinder a successful clinical translation of MSC-based therapies, including but not limited to heterogeneity of their populations, variability in their quality and quantity, donor-related factors, discrepancies in protocols for isolation, in vitro expansion and premodification, and variability in methods of cell delivery, dosing, and cell homing. Alterations of MSC viability, proliferation, properties, and/or function are also affected by various drugs and chemicals. Moreover, significant safety concerns exist due to possible teratogenic/neoplastic potential and transmission of infectious diseases. Through the current review, we aim to highlight the major challenges facing MSCs’ human clinical translation and shed light on the undergoing strategies to overcome them.

El Moshy, S., I. A. Radwan, D. Rady, M. M. S. Abbass, A. A. El-Rashidy, K. M. Sadek, C. E. Dörfer, and K. M Fawzy El-Sayed, "Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications.", Stem cells international, vol. 2020, pp. 7593402, 2020. Abstract

Regenerative medicine literature has proposed mesenchymal stem/progenitor cell- (MSC-) mediated therapeutic approaches for their great potential in managing various diseases and tissue defects. Dental MSCs represent promising alternatives to nondental MSCs, owing to their ease of harvesting with minimally invasive procedures. Their mechanism of action has been attributed to their cell-to-cell contacts as well as to the paracrine effect of their secreted factors, namely, secretome. In this context, dental MSC-derived secretome/conditioned medium could represent a unique cell-free regenerative and therapeutic approach, with fascinating advantages over parent cells. This article reviews the application of different populations of dental MSC secretome/conditioned medium in in vitro and in vivo animal models, highlights their significant implementation in treating different tissue' diseases, and clarifies the significant bioactive molecules involved in their regenerative potential. The analysis of these recent studies clearly indicate that dental MSCs' secretome/conditioned medium could be effective in treating neural injuries, for dental tissue regeneration, in repairing bone defects, and in managing cardiovascular diseases, diabetes mellitus, hepatic regeneration, and skin injuries, through regulating anti-inflammatory, antiapoptotic, angiogenic, osteogenic, and neurogenic mediators.

El-Rashidy, A. A., J. A. Roether, L. Harhaus, U. Kneser, and A. R. Boccaccini, "Regenerating bone with bioactive glass scaffolds: A review of in vivo studies in bone defect models", Acta Biomaterialia, vol. 62, pp. 1-28, 2017.
El-Rashidy, A. A., G. Waly, A. Gad, A. A. Hashem, P. Balasubramanian, S. Kaya, A. R. Boccaccini, and I. Sami, "Preparation and in vitro characterization of silver-doped bioactive glass nanoparticles fabricated using a sol-gel process and modified Stöber method", Journal of Non-Crystalline Solids, vol. 483, pp. 26-36, 2018.
El-Rashidy, A. A., G. Waly, A. Gad, J. A. Roether, J. Hum, Y. Yang, R. Detsch, A. A. Hashem, I. Sami, W. H. Goldmann, et al., "Antibacterial activity and biocompatibility of zein scaffolds containing silver-doped bioactive glass.", Biomedical materials (Bristol, England), vol. 13, issue 6, pp. 065006, 2018 Aug 24. Abstract

Composite 3D scaffolds combining natural polymers and bioceramics are promising candidates for bone tissue engineering (BTE). Zein, as a natural plant protein, offers several advantages, including biocompatibility, adequate strength properties, and low/no immunogenicity; however, it lacks bioactivity. Thus, composite zein: bioactive glass (BG) scaffolds are proposed as promising candidate for BTE applications, with silver-doping of bioactive glass providing an antibacterial effect against possible post-implantation infection. Therefore, the aim of this study was to investigate the in vitro antibacterial properties, biocompatibility, bioactivity and compressive strength of zein scaffolds containing silver-doped bioactive glass. BG nanoparticles, undoped and Ag-doped, were fabricated using the sol-gel method. 3D composite zein:BG scaffolds, containing 20 wt% BG, were prepared and their antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was assessed using the disc diffusion assay. Human osteoblast-like MG-63 cells were used to evaluate the in vitro biocompatibility of the prepared scaffold groups. In addition, the compressive strength of the scaffolds was determined using uniaxial compression strength testing and the scaffold interconnected porosity was measured using helium pycnometer. Disc diffusion assay showed that only zein scaffolds containing Ag-doped sol-gel BG are antibacterially positive against E. coli and S. aureus. Pure zein scaffolds and zein scaffolds containing sol-gel-derived BG showed no negative influence on the growth of MG-63 cells, as evident by the cells' ability to survive, proliferate, and function on these scaffolds. Moreover, incorporating sol-gel-derived BG into zein scaffolds at zein:BG of 80:20 ratio showed bioactive properties with adequate porosity without affecting the scaffolds' compressive strengths, which was similar to that of trabecular bone, suggesting that the new composites have potential for BTE applications in non-loaded bearing areas.

El-Rashidy, A. A., A. Gad, A. E. - H. G. Abu-Hussein, S. I. Habib, N. A. Badr, and A. A. Hashem, "Chemical and biological evaluation of Egyptian Nile Tilapia (Oreochromis niloticas) fish scale collagen", International Journal of Biological Macromolecules, vol. 79, pp. 618–626, 2015.
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