Seaweed polysaccharides as macromolecular crowding agents.

Development of mesenchymal stem cell-based tissue engineered implantable devices requires prolonged in vitro culture for the development of a three-dimensional implantable device, which leads to phenotypic drift, thus hindering the clinical translation and commercialisation of such approaches. Macromolecular crowding, a biophysical phenomenon based on the principles of excluded-volume effect, dramatically accelerates and increases extracellular matrix deposition during in vitro culture. However, the optimal macromolecular crowder is still elusive. Herein, we evaluated the biophysical properties of various concentrations of different seaweed in origin sulphated polysaccharides and their effect on human adipose derived stem cell cultures. Carrageenan, possibly due to its high sulphation degree, exhibited the highest negative charge values. No correlation was observed between the different concentrations of the crowders and charge, polydispersity index, hydrodynamic radius and fraction volume occupancy across all crowders. None of the crowders, but arabinogalactan, negatively affected cell viability. Carrageenan, fucoidan, galactofucan and ulvan increased extracellular matrix (especially collagen type I and collagen type V) deposition. Carrageenan induced the highest osteogenic effect and galactofucan and fucoidan demonstrated the highest chondrogenic effect. All crowders were relatively ineffective with respect to adipogenesis. Our data highlight the potential of sulphated seaweed polysaccharides for tissue engineering purposes.

The effect of aligned electrospun fibers and macromolecular crowding in tenocyte culture.

Tendon injuries continuously rise, and regeneration is not only slow, but also limited due to the poor endogenous healing ability of the tendon tissue. Tissue grafts constitute the clinical gold standard treatment for severe injuries, but inherent limitations drive the field toward tissue engineering approaches to create suitable tissue constructs. Recapitulation of the native microenvironment represent a key challenge for the development of tendon tissue equivalents in vitro that can be further utilized as implantable devices. Methods to maintain cellular phenotype and to enhance extracellular matrix deposition for accelerated development of tissue-like modulus should be developed. Herein, we assessed the combining effect of surface topography and macromolecular crowding in human tenocyte culture. Our data demonstrated that bidirectionally aligned electrospun fibers induce physiological cell growth, while macromolecular crowding enhanced and accelerated tissue-specific extracellular matrix deposition. Collectively, these data advocate the use of multifactorial approaches for the accelerated development of functional tissue-like surrogates in vitro.

Bioresponsive drug delivery systems in intestinal inflammation: State-of-the-art and future perspectives.

Oral colon-specific delivery systems emerged as the main therapeutic cargos by making a significant impact in the field of modern medicine for local drug delivery in intestinal inflammation. The site-specific delivery of therapeutics (aminosalicylates, glucocorticoids, biologics) to the ulcerative mucus tissue can provide prominent advantages in mucosal healing (MH). Attaining gut mucosal healing and anti-fibrosis are main treatment outcomes in inflammatory bowel disease (IBD). The pharmaceutical strategies that are commonly used to achieve a colon-specific drug delivery system include time, pH-dependent polymer coating, prodrug, colonic microbiota-activated delivery systems and a combination of these approaches. Amongst the different approaches reported, the use of biodegradable polysaccharide coated systems holds great promise in delivering drugs to the ulcerative regions. The present review focuses on major physiological gastro-intestinal tract challenges involved in altering the pharmacokinetics of delivery systems, pathophysiology of MH and fibrosis, reported drug-polysaccharide cargos and focusing on conventional to advanced disease responsive delivery strategies, highlighting their limitations and future perspectives in intestinal inflammation therapy.