With the increasing growth of the algae industry and the development of algae biorefinery, there is a growing need for high-value applications of algae-extracted biopolymers. The utilization of such biopolymers in the biomedical field can be considered as one of the most attractive applications but is challenging to implement. Historically, polysaccharides extracted from seaweed have been used for a long time in biomedical research, for example, agarose gels for electrophoresis and bacterial culture. To overcome the current challenges in polysaccharides and help further the development of high-added-value applications, an overview of the entire polysaccharide journey from seaweed to biomedical applications is needed. This encompasses algae culture, extraction, chemistry, characterization, processing, and an understanding of the interactions of soft matter with living organisms. In this review, we present algae polysaccharides that intrinsically form hydrogels: alginate, carrageenan, ulvan, starch, agarose, porphyran, and (nano)cellulose and classify these by their gelation mechanisms. The focus of this review further lays on the culture and extraction strategies to obtain pure polysaccharides, their structure-properties relationships, the current advances in chemical backbone modifications, and how these modifications can be used to tune the polysaccharide properties. The available techniques to characterize each organization scale of a polysaccharide hydrogel are presented, and the impact on their interactions with biological systems is discussed. Finally, a perspective of the anticipated development of the whole field and how the further utilization of hydrogel-forming polysaccharides extracted from algae can revolutionize the current algae industry are suggested.

Significance: Nanoparticles (NPs) can serve as containers for the targeting of therapeutics to tumors. Tumors comprise many cell types including endothelial cells that form the blood vessels. Developing new strategies to target information preferentially to endothelial cells can have major implications in the development of targeted therapeutics. We have discovered that charged polymers containing aromatic sulfonate have pronounced affinity for caveolae, which are highly expressed by endothelial cells. By engineering the surface of lipid NPs to bear sulfonate-containing polymers, lipid NPs that are preferentially taken up by endothelial cells have been demonstrated.

Significance: The role of soluble signals in neural differentiation and neurodegeneration is well established. However, the impact of nanotopography imposed by macromolecules within brain tissue on neuronal function and pathologies is not fully appreciated. We have discovered that nanoroughness can modulate the function of hippocampal neurons and their relationship with astrocytes. Inhibition of mechanosensing cation channels including Piezo-1, whose distribution is altered by nanotopography, abrogates the effects imposed by nanotopography and the association of neurons with astrocytes. The finding that regions of amyloid plaque buildup in Alzheimer’s involve changes to tissue nanoroughness provides a link between nanoscale physical cues and loss of function in neurons and may have implications in uncovering the factors that promote neurodegenerative diseases.

Polymers have a long history in medicine. Their uses to date range from traditional applications such as catheters, syringes, blood contacting extra corporeal devices to matrices for drug delivery, cell encapsulation and tissue regeneration. Polymers can be broadly classified on the basis of the reactivity of their chemical backbone (or susceptibility of the backbone to breakdown upon exposure to water, i.e., hydrolysis) as non-degradable and degradable. In this review, the polymers that exhibit no to very low degradation in aqueous and biological environments will be covered. The applications of various polymers both in traditional and emerging medical areas is discussed in the context of its chemical structure to better enable material selection for biomedical research.

Matrix-metalloproteinases 9 (MMP-9) belongs to the class of matrix metalloproteinases whose main function is to degrade and remodel the extracellular matrix (ECM). MMP-9 has been shown to be an integral part of many diseases where modulation of the ECM is a key step such as cancer, osteoporosis and fibrosis. MMP-9 is secreted as a latent pro-enzyme that requires activation in the extracellular space. Therefore, identifying physiological and molecular contexts, which can activate MMP-9 is important. Acidification of osteoclast-conditioned media to pH 5 resulted in a fragment with a size corresponding to active MMP-9. Also, treatment of recombinant proMMP-9 with recombinant cathepsin K (CTSK) at pH 5 yielded a fragment that corresponded to the molecular weight of active MMP-9, and showed MMP-9 activity. This activation was abrogated in the presence of CTSK inhibitor indicating that CTSK was responsible for the activation of pro-MMP-9. Knocking down CTSK in MDA-MB-231 cells also diminished MMP-9 activity compared to wild type control. Here we provide the first evidence that CTSK can cleave and activate MMP-9 in acidic environments such as seen in tumors and during bone resorption. This finding provides a key link between CTSK expression in tumors and bone and ECM remodeling, through MMP-9 activation. This novel mechanism to activate MMP-9 through extracellular physiological changes elucidated in this study reveals a protease-signaling network involving CTSK and MMP-9 and provides the impetus to explore ECM proteases as physiological markers and pharmacological targets.