Due to the limitations of bone autografts, we aimed to develop new composite biomaterials with pro-angiogenic and osteogenic properties to be used as scaffolds in bone tissue engineering applications. We used a porous, cross-linked and slowly biodegradable fibrin/alginate scaffold originally developed in our laboratory for wound healing, throughout which deposits of calcium phosphate (CaP) were evenly incorporated using an established biomimetic method. Material characterisation revealed the porous nature and confirmed the deposition of CaP precursor phases throughout the scaffolds. MC3T3-E1 cells adhered to the scaffolds, proliferated, migrated and differentiated down the osteogenic pathway during the culture period. Chick chorioallantoic membrane (CAM) assay results showed that the scaffolds were pro-angiogenic and biocompatible. The work presented here gave useful insights into the potential of these pro-angiogenic and osteogenic scaffolds for bone tissue engineering and merits further research in a pre-clinical model prior to its clinical translation.

Biomaterial development for clinical applications is currently on the rise. This necessitates adequate in vitro testing, where the structure and composition of biomaterials must be specifically tailored to withstand in situ repair and regeneration responses for a successful clinical outcome. The chorioallantoic membrane of chicken embryos has been previously used to study angiogenesis, a prerequisite for most tissue repair and regeneration. In this study, we report an optimised ex ovo method using a glass-cling film set-up that yields increased embryo survival rates and has an improved protocol for harvesting biomaterials. Furthermore, we used this method to examine the intrinsic angiogenic capacity of a variety of biomaterials categorised as natural, synthetic, natural/synthetic and natural/natural composites with varying porosities. We detected significant differences in biomaterials’ angiogenesis with natural polymers and polymers with a high overall porosity showing a greater vascularisation compared to synthetic polymers. Therefore, our proposed ex ovo chorioallantoic membrane method can be effectively used to pre-screen biomaterials intended for clinical application.

We hypothesized that a composite of 3D porous melt-electrowritten poly-ɛ-caprolactone (PCL) coated throughout with a porous and slowly biodegradable fibrin/alginate (FA) matrix would accelerate bone repair due to its angiogenic potential. Scanning electron microscopy showed that the open pore structure of the FA matrix was maintained in the PCL/FA composites. Fourier transform infrared spectroscopy and differential scanning calorimetry showed complete coverage of the PCL fibres by FA, and the PCL/FA crystallinity was decreased compared with PCL. In vitro cell work with osteoprogenitor cells showed that they preferentially bound to the FA component and proliferated on all scaffolds over 28 days. A chorioallantoic membrane assay showed more blood vessel infiltration into FA and PCL/FA compared with PCL, and a significantly higher number of bifurcation points for PCL/FA compared with both FA and PCL. Implantation into a rat cranial defect model followed by microcomputed tomography, histology, and immunohistochemistry after 4- and 12-weeks post operation showed fast early bone formation at week 4, with significantly higher bone formation for FA and PCL/FA compared with PCL. However, this phenomenon was not extrapolated to week 12. Therefore, for long-term bone regeneration, tuning of FA degradation to ensure syncing with new bone formation is likely necessary.

The regenerative capacity of mesenchymal stem cells (MSCs) is now attributed to their ability to release paracrine factors into the extracellular matrix that boost tissue regeneration, reduce inflammation and encourage healing. Understanding the MSC secretome is crucial for shifting the prototypic conventional cell-based therapies to cell-free regenerative treatments. This systematic review aimed to analyse the functional annotations of the secretome of human adult adipose tissue and bone marrow MSCs and unveil the gene clusters responsible for bone formation. Bioinformatics tools were used to identify the biological processes, molecular functions, hallmarks and KEGG pathways of adipose and bone marrow MSC secretome proteins. We found a substantial overlap in the functional annotations and protein compositions of both adipose and bone marrow MSC secretome indicating that MSC source may be noninfluencial with regards to tissue regeneration. Additionally, a novel network pharmacology-based analysis of the secreted proteins revealed that the commonly secreted proteins within a single source interact with multiple drugable targets of bone diseases and regulate various KEGG pathway. This study unravels the secretome profile of human adult adipose and bone marrow MSCs based on the current literature and provides valuable insights into the therapeutic use of the MSC secretome for cell-free therapies.

This communication reports preliminary data towards the development of a live ex vivo model of persistent infection that is based on the chick embryo chorioallantoic membrane (CAM), which can be used for pre-screening biomaterials with antimicrobial properties for their antimicrobial and angiogenic potential. Our results showed that it was possible to infect chicken embryos with Staphylococcus aureus, one of the main types of bacteria found in the persistent infection associated with chronic wounds, and maintain the embryos’ survival for up to 48 h. Survival of the embryos varied with the dose of bacteria inoculum and with the use and time of streptomycin application after infection. In infected yet viable embryos, the blood vessels network of the CAM was maintained with minimal disruption. Microbiological tests could confirm embryo infection, but quantification was difficult. By publishing these preliminary results, we hope that not only our group but others within the scientific community further this research towards the establishment of biomimetic and reproducible ex vivo models of persistent infection.

Rheumatoid arthritis (RA) is a multifaceted autoimmune disease that is marked by a complex molecular profile influenced by an array of factors, including genetic, epigenetic, and environmental elements. Despite significant advancements in research, the precise etiology of RA remains elusive, presenting challenges in developing innovative therapeutic markers. This study takes an integrated multi-omics approach to uncover novel therapeutic markers for RA. By analyzing both transcriptomics and epigenomics datasets, we identified common gene candidates that span these two omics levels in patients diagnosed with RA. Remarkably, we discovered eighteen multi-evidence genes (MEGs) that are prevalent across transcriptomics and epigenomics, twelve of which have not been previously linked directly to RA. The bioinformatics analyses of the twelve novel MEGs revealed they are part of tightly interconnected protein–protein interaction networks directly related to RA-associated KEGG pathways and gene ontology terms. Furthermore, these novel MEGs exhibited direct interactions with miRNAs linked to RA, underscoring their critical role in the disease’s pathogenicity. Overall, this comprehensive bioinformatics approach opens avenues for identifying new candidate markers for RA, empowering researchers to validate these markers efficiently through experimental studies. By advancing our understanding of RA, we can pave the way for more effective therapies and improved patient outcomes.