Extracellular matrix (ECM) hydrogel promotes tissue regeneration in lesion cavities after stroke. However, a bioscaffold's regenerative potential needs to be considered in the context of the evolving pathological environment caused by a stroke. To evaluate this key issue in rats, ECM hydrogel was delivered to the lesion core/cavity at 7-, 14-, 28-, and 90-days post-stroke. Due to a lack of tissue cavitation 7-days post-stroke, implantation of ECM hydrogel did not achieve a sufficient volume and distribution to warrant comparison with the other time points. Biodegradation of ECM hydrogel implanted 14- and 28-days post-stroke were efficiently (80%) degraded by 14-days post-bioscaffold implantation, whereas implantation 90-days post-stroke revealed only a 60% decrease. Macrophage invasion was robust at 14- and 28-days post-stroke but reduced in the 90-days post-stroke condition. The pro-inflammation (M1) and pro-repair (M2) phenotype ratios were equivalent at all time points, suggesting that the pathological environment determines macrophage invasion, whereas ECM hydrogel defines their polarization. Neural cells (neural progenitors, neurons, astrocytes, oligodendrocytes) were found at all time points, but a 90-days post-stroke implantation resulted in reduced densities of mature phenotypes. Brain tissue restoration is therefore dependent on an efficient delivery of a bioscaffold to a tissue cavity, with 28-days post-stroke producing the most efficient biodegradation and tissue regeneration, whereas by 90-days post-stroke, these effects are significantly reduced. Improving our understanding of how the pathological environment influences biodegradation and the tissue restoration process is hence essential to devise engineering strategies that could extend the therapeutic window for bioscaffolds to repair the damaged brain.
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http://dx.doi.org/10.3390/ijms222111372 | DOI Listing |
Cell Biochem Biophys
December 2024
School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, 464-8650, Japan.
Cell-extracellular matrix (ECM) interactions play multiple roles in developmental, physiological, and pathological processes. ECM stiffness substantially affects cellular morphology, migration, and function. In this study, we investigated the effect of ECM comprising gelatin methacryloyl (GelMA) on the activation of rat basophilic leukemia (RBL-2H3) cells, a model mast cell line.
View Article and Find Full Text PDFGels
December 2024
Biointerface Laboratory, Helmholtz-Institut for Biomedical Engineering, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
Angiogenesis, the formation of new blood vessels, is a fundamental process in both physiological repair mechanisms and pathological conditions, including cancer and chronic inflammation. Hydrogels are commonly used as in vitro models to mimic the extracellular matrix (ECM) and support endothelial cell behavior during angiogenesis. Mesenchymal stem cells further augment cell and tissue growth and are therefore widely used in regenerative medicine.
View Article and Find Full Text PDFGels
November 2024
Department of Removable Prosthodontics and Occlusion, Osaka Dental University, 8-1, Kuzuhahanazono-cho, Hirakata-shi 573-1121, Osaka, Japan.
Bone tissue engineering is a technique that simulates the bone tissue microenvironment by utilizing cells, tissue scaffolds, and growth factors. The collagen hydrogel is a three-dimensional network bionic material that has properties and structures comparable to those of the extracellular matrix (ECM), making it an ideal scaffold and drug delivery system for tissue engineering. The clinical applications of this material are restricted due to its low mechanical strength.
View Article and Find Full Text PDFJ Biomed Mater Res A
January 2025
Department of Bioengineering, Stanford University, Stanford, California, USA.
Osteoarthritis (OA) is a prevalen degenerative joint disease with no FDA-approved therapies that can halt or reverse its progression. Current treatments address symptoms like pain and inflammation, but not underlying disease mechanisms. OA progression is marked by increased inflammation and extracellular matrix (ECM) degradation of the joint cartilage.
View Article and Find Full Text PDFMethods Mol Biol
December 2024
Department of Chemistry, North Carolina State University, Raleigh, NC, USA.
Extracellular matrix (ECM) from decellularized mammalian tissues has been used in many therapeutic applications. The tissue-specific composition of the ECM is critically associated with therapeutic performance. However, ECM translation needs to be improved because of the complex composition and limited understanding of ECM repairing mechanisms due partly to incomplete proteomic interrogation of ECM samples.
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