The activity of stem cell processes is regulated by internal and external signals of the cell “niche”. In general, the niche of stem cells can be represented as the microenvironment of the cells, providing a signal complex, determining the properties of the cells. At the same time, the “niche” concept implies feedback. Cells can modify their microenvironment, supporting homeostasis or remodeling the composition and structure of the extracellular matrix. To ensure the regenerative potential of tissue engineering products the “niche” concept should be taken into account. To investigate interactions in an experimental niche, an original hydrogel biopolymer scaffold with encapsulated mesenchymal adipose-derived stem cells (ASCs) was used in this study. The scaffold provides for cell adhesion, active cell growth, and proliferative activity. Cells cultured within a scaffold are distinguished by the presence of a developed cytoskeleton and they form a cellular network. ASCs cultured within a scaffold change their microenvironment by secreting VEGF-A and remodeling the scaffold structure. Scaffold biodegradation processes were evaluated after previous culturing of the ASCs in the scaffolds for periods of either 24 h or six days. The revealed differences confirmed that changes had occurred in the properties of scaffolds remodeled by cells during cultivation. The mechanisms of the identified changes and the possibility of considering the presented scaffold as an appropriate artificial niche for ASCs are discussed.
Biopolymers, in particular collagen and fibrinogen, are the leading materials for use in tissue engineering. When developing technology for scaffold formation, it is important to understand the properties of the source materials as well as the mechanisms that determine the formation of the scaffold structures. Both factors influence the properties of scaffolds to a great extent. Our present work aimed to identify the features of the molecular characteristics of collagens of different species origin and the changes they undergo during the enzymatic hydrolysis used for the process of scaffold formation. For this study, we used the methods of gel-penetrating chromatography, dynamic light scattering, reading IR spectra, and scanning electron microscopy. It was found that cod collagen (CC) and bovine collagen (BC) have different initial molecular weight parameters, and that, during hydrolysis, the majority of either type of protein is hydrolyzed by the proteolytic enzymes within the first minute. The differently sourced collagen samples were also hydrolyzed with the formation of two low molecular fractions: Mw ~ 10 kDa and ~20 kDa. In the case of CC, the microstructure of the final scaffolds contained denser, closely spaced fibrillar areas, while the BC-sourced scaffolds had narrow, short fibrils composed of unbound fibers of hydrolyzed collagen in their structure.
The success of the regenerative process resulting from the implantation of a scaffold or a tissue-engineered structure into damaged tissues depends on a series of factors, including, crucially, the biodegradability of the implanted materials. The selection of a scaffold with appropriate biodegradation characteristics allows for synchronization of the degradation of the construct with the processes involved in new tissue formation. Thus, it is extremely important to characterize the biodegradation properties of potential scaffold materials at the stage of in vitro studies. We have analyzed the biodegradation of hybrid fibrin–collagen scaffolds in both PBS solution and in trypsin solution and this has enabled us to describe the processes of both their passive and enzymatic degradation. It was found that the specific origin of the collagen used to form part of the hybrid scaffolds could have a significant effect on the nature of the biodegradation process. It was also established, during comparative studies of acellular scaffolds and scaffolds containing stem cells, that the cells, too, make a significant contribution to changes in the biodegradation and structural properties of such scaffolds. The study results also provided evidence indicating the dependency between the pre-cultivation period for the cellular scaffolds and the speed and extent of their subsequent biodegradation. Our discussion of results includes an attempt to explain the mechanisms of the changes found. We hope that the said results will make a significant contribution to the understanding of the processes affecting the differences in the biodegradation properties of hybrid, biopolymer, and hydrogel scaffolds.
The article updates the existing data on the use of scaffolds as target and controlled substance delivery systems. The prerequisites and grounds for using scaffolds as substance delivery systems are being considered. Current tissue-engineered strategies for developing target drug and bioactive substance delivery using scaffolds are being discussed. A classification of scaffold-based substance delivery systems is provided. Special attention is given to the development of two-phase substance delivery systems using various types of nanoparticles. A variety of nanoparticles and the benefits of their use as carriers of substances in a two-component delivery systems are shown. Recent developments in the substance delivery systems for regenerative medicine and future prospects are presented.
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