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Flaviviruses such as dengue, Zika, West Nile, and yellow fever are dangerous viruses that pose a significant global health burden and have massive epidemic potential. Annually, these viruses infect over 400 million individuals worldwide and have been responsible for several pandemics in recent years. Flavivirus infection can result in hepatitis, microcephaly, liver cirrhosis, hemorrhagic shock, and even death. Despite these severe consequences, there are no available therapeutics for the majority of these flaviviruses . The initial response to flavivirus infection is characterized by the mass production of pro-inflammatory molecules in the host’s attempt to defend against pathogen invasion, causing widespread tissue damage through a phenomenon known as a cytokine storm. Consequently, it is crucial to investigate the host immune regulators that govern inflammatory multi-protein complexes called inflammasomes. Previous studies have highlighted the role of Nod-Like Receptor Protein 10 (NLRP10) in suppressing inflammation by inhibiting another human protein called pro-caspase-1 (pro-CASP1), a key component of many inflammasome systems. Therefore, we sought to determine what role NLRP10 played in the context of flavivirus-associated inflammation. Our findings reveal that NLRP10 is cleaved by diverse flavivirus proteases at amino acid site 265. However, this cleavage did not result in the restoration of inflammasome activation. Despite this, we also discovered that flaviviruses also independently antagonize inflammasomes. Collectively, our results demonstrate that flaviviruses exert evolutionary pressures on many inflammasome-associated proteins such as NLRP10, highlighting the intricacy of virus-host dynamics on a broader pan-flavivirus scale.

Focal chondral defects that result from traumatic injuries to the knee remain one of the most common causes of disability in patients. Current solutions for healing focal cartilage defects are mainly limited by the production of inferior cartilage-like tissue and subsequent delamination due to incomplete healing of the subchondral bone. In this experiment a polymeric osteochondral implant for guiding autologous bone marrow stem cells (BMSCs) to populate the scaffold to create distinctive bone and cartilage tissue is used. The cartilage component presents bioactive aligned nanofibers containing chondroitin sulfate and hyaluronic acid while the bone component includes hydroxyapatite to promote chondrogenic and osteogenic differentiation of the rat BMSCs in vitro. The different cartilage and bone components resulted in the elevated expression of osteogenic markers such as bone sialoprotein, runt related transcription factor 2, and bone morphogenetic protein 2 in the deeper bone layer and chondrogenic markers such as collagen type II and aggrecan in the cartilage layer. Through immunofluorescence imaging, the alignment of the secreted collagen type II fibrils and aggrecan was visualized and quantified on the cartilage component of the scaffold. These current studies show that the biodegradable biphasic osteochondral implant may be effective in promoting more hyaline-like tissue to fill in chondral defects of the knee.

Cartilage degeneration is the major cause of disability and poses several challenges to repair and regenerate. Conventional surgical treatments often induce fibrous tissues and compromise its function. Alternative tissue engineering strategies utilized scaffolds, factors and cells alone or in combination with some degree of success. This study reports the use of nanostructured biomimetic scaffold system in regulating the rat bone marrow stem cells (rBMSCs) differentiation into chondrogenic lineage in vitro. The biometric scaffold is essentially a micro-porous polycaprolactone (PCL) spiral structure decorated with sparsely spaced bioactive PCL nanofibers. The bioactivity stems from the use of two major components of hyaline cartilage extracellular matrix (ECM) namely chondroitin sulfate (CS) and hyaluronic acid (HYA). The PCL spiral structure was surface functionalized with PCL nanofibers encapsulated with CS (20% (w/w)) and HYA (0.2% (w/w)). In order to retain and sustain the release of CS and HYA nanofibers were cross-linked using carbodiimide chemistry. This study also evaluated the effect of nanofiber alignment on rBMSCs differentiation and evaluated the production of characteristic hyaline cartilage proteins namely collagen type II and aggrecan in vitro up to 28 days. Rat bone marrow derived stem cells cultured on the aligned nanofibers expressed significantly elevated levels of collagen type II and aggrecan secretions (western blots) as compared to scaffolds decorated with random fibers and tissue culture polystyrene (TCPS). This fiber alignment dependent expression of collagen type II and aggrecan secretion were further confirmed through immunofluorescence staining. This biomimetic and bioactive scaffold may serve as a serve as an efficient scaffold system for cartilage regeneration.

Polymeric biomaterials have been extensively studied and optimized for biomedical applications. In the recent two decades, research has become more focused on translational clinical applications, especially tissue engineering and regenerative medicine. This chapter reviews major polymeric biomaterials, based on their diverse biomedical uses with a focus on regenerative tissue engineering. The polymers are divided into two classes: natural polymers and synthetic polymers, along with a comparison of their advantages and disadvantages. Synthetic polymers lend themselves to chemical modifications and are relatively versatile and customizable to specific needs, while natural polymers are more abundant and resemble the components present in extracellular matrices. A brief description of the physical, chemical, and biological properties of polymers is given, all of which are closely related to applications. Most of the polymers, polymer derivatives, blends, or copolymers are reported to retain their favorable characteristics suitable for tissue/regenerative engineering. Examples of applications involving repairing damaged tissues include the repair of cartilage, skin, bladder, muscle, neurite, bone, and blood vessels.