iBB

As current treatments for periodontitis have failed to promote tissue repair and the coordinated regeneration of the whole periodontium, innovative therapeutic strategies are urgently needed to improve the clinical outcomes. Electrospun nanofibrous scaffolds are particularly promising for applications in periodontal regeneration since they are able to mimic the native tissue extracellular matrix (ECM) features such as the size and alignment of the fibers present in the periodontal ligament (PDL). In this article recently published in the journal Nanomaterials, iBB researchers MSc Mafalda Santos, Dr. Marta Carvalho and Dr. João Silva provided an overview of the current state of the art of the application of electrospun nanofibers in periodontal regeneration, either as guided tissue regeneration (GTR) membranes or as scaffolds for tissue engineering strategies.

There is a high demand for functional bone grafts worldwide partly due to the increased life expectancy. Bone matrix proteins, especially osteopontin (OPN) and osteocalcin (OC), have been reported to regulate some physiological process, such as cell migration and bone mineralization. However, the effects of OPN and OC on cell proliferation, osteogenic differentiation, mineralization and angiogenesis are still undefined.  In a recent study published in Journal of Cellular and Biochemistry, researchers from SCERG-iBB working with colleagues from the Rensselaer Polytechnic Institute assessed the exogenous effect of OPN and OC supplementation on human bone marrow mesenchymal stem/stromal cells proliferation and osteogenic differentiation.  These results suggest that OC and OPN stimulate bone regeneration by inducing stem cell proliferation, osteogenesis and by enhancing angiogenic properties. The synergistic effect of OC and OPN observed in this study can be applied as an attractive strategy for bone regeneration therapeutics by targeting different vital cellular processes.

Cell-derived extracellular matrix (ECM) has been employed as scaffolds for tissue engineering. SCERG-iBB researchers working with colleagues from the Rensselaer Polytechnic developed bioactive cell-derived ECM electrospun polycaprolactone (PCL) scaffolds produced from ECM derived from human mesenchymal stem/stromal cells (MSC), human umbilical vein endothelial cells (HUVEC) and their combination based on the hypothesis that the cell-derived ECM incorporated into the PCL fibers would enhance the biofunctionality of the scaffold. The findings show that all cell-derived ECM electrospun scaffolds promoted significant cell proliferation compared to PCL alone, while presenting similar physical/mechanical properties. Additionally, MSC:HUVEC-ECM electrospun scaffolds significantly enhanced osteogenic differentiation of MSCs. The study was published in Materials Science and Engineering: C.

The project "DentalBioMatrix: Exploiting the power of decellularized extracellular matrix to fabricate hierarchical biomimetic scaffolds to regenerate functional periodontal tissues" has been recommended for funding by FCT (2020 Call for SR&TD Project Grants). The goal of DentalBioMatrix is to develop novel bioengineering strategies to regenerate periodontium, by engineering hierarchically designed compartmentalized systems to meet the different characteristics of the tissues involved in periodontal defects. Decellularized extracellular matrix (dECM) will be used to create complex dECM-derived scaffolds to recreate the different niches of periodontium. Collectively, this approach will potentially provide the opportunity to harness the properties of periodontal tissue ECM, recreating a local niche at the tooth interface that can promote periodontal regeneration, especially important for osteoporotic and older patients with compromised ECM. The project, which falls within the scientific area of Medical Biotechnology, is headed by Marta Carvalho from SCERG-iBB.

Cell-derived ECM have emerged as promising materials for regenerative medicine due to their ability to recapitulate the native tissue microenvironment. However, little is known about the glycosaminoglycan (GAG) composition of these cell-derived ECM. In a recent study published in Glycoconjugate Journal, researchers from SCERG-iBB, working in collaboration with colleagues from the Rensselaer Polytechnic Institute, characterized three different cell-derived ECM in terms of their GAG content, composition and sulfation patterns using a highly sensitive LC-MS/MS technique. Distinct GAG compositions and disaccharide sulfation patterns were verified for the different cell-derived ECM. Additionally, the effect of decellularization method on the GAG and disaccharide relative composition was also assessed. The method offers a novel approach to determine the GAG composition of cell-derived ECM, which we believe is critical for a better understanding of ECM role in directing cellular responses and has the potential for generating important knowledge for the development of new ECM-like biomaterials for tissue engineering applications.