Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP), which results in disability worldwide. However, the pathogenesis of IVD degeneration mediating LBP remains unclear. Current conservative treatments and surgical interventions are both to relieve the symptoms and minimise pain; nevertheless, they are unable to reverse the degeneration. Previous studies have shown that inflammation and nociception markers are important indicators of pain mechanisms in IVD degeneration underlying LBP. As such, multiomics profiling allows the discovery of these target markers to understand the key pathological mechanisms mediating IVD degeneration underpinnings of LBP. This article provides insights into a precision medicine approach for identifying and understanding the pathophysiology of IVD degeneration associated with LPB based on the severity of the disease from early and mild to severe degenerative stages. Molecular profiling of key markers in degenerative IVDs based on patient stratification at early, mild, and severe stages will contribute to the identification of target markers associated with signalling pathways in mediating neuroinflammation, innervation, and nociception underlying painful IVD degeneration. This approach will offer an understanding of establishing personalised clinical strategies tailored to the severity of IVD degeneration for the treatment of LBP.
In recent years, the development of hyaluronic acid or hyaluronan (HA) based scaffolds, medical devices, bioconjugate systems have expanded into a broad range of research and clinical applications. Research findings over the last two decades suggest that the abundance of HA in most mammalian tissues with distinctive biological roles and chemical simplicity for modifications have made it an attractive material with a rapidly growing global market. Besides its use as native forms, HA has received much interest on so-called "HA-bioconjugates" and "modified-HA systems". In this review, the importance of chemical modifications of HA, underlying rationale approaches, and various advancements of bioconjugate derivatives with their potential physicochemical, and pharmacological advantages are summarized. This review also highlights the current and emerging HA-based conjugates of small molecules, macromolecules, crosslinked systems, and surface coating strategies with their biological implications, including their potentials and key challenges discussed in detail.
The diatom's frustule, characterized by its rugged and porous exterior, exhibits a remarkable biomimetic morphology attributable to its highly ordered pores, extensive surface area, and unique architecture. Despite these advantages, the toxicity and nonbiodegradable nature of silica-based organisms pose a significant challenge when attempting to utilize these organisms as nanotopographically functionalized microparticles in the realm of biomedicine. In this study, we addressed this limitation by modulating the chemical composition of diatom microparticles by modulating the active silica metabolic uptake mechanism while maintaining their intricate three-dimensional architecture through calcium incorporation into living diatoms. Here, the diatom Thalassiosira weissflogii was chemically modified to replace its silica composition with a biodegradable calcium template, while simultaneously preserving the unique three-dimensional (3D) frustule structure with hierarchical patterns of pores and nanoscale architectural features, which was evident by the deposition of calcium as calcium carbonate. Calcium hydroxide is incorporated into the exoskeleton through the active mechanism of calcium uptake via a carbon-concentrating mechanism, without altering the microstructure. Our findings suggest that calcium-modified diatoms hold potential as a nature-inspired delivery system for immunotherapy through antibody-specific binding.
Introduction: A regenerative strategy employing extracellular matrix (ECM)-based biomaterials and stem cells provide a better approach to mimicking the three-dimensional (3D) microenvironment of intervertebral disc for endogenous tissue regeneration. However, there is currently limited understanding regarding the human Wharton Jelly derived-mesenchymal stem cells (hWJ-MSCs) towards nucleus pulposus (NP)-like cells. Our study focused on the development of 3D bioengineered hydrogel based on the predominant ECM of native NP, including type II collagen (COLII) and hyaluronic acid (HA), which aims to tailor the needs of the microenvironment in NP. Methods: We have fabricated a 3D hydrogel using from COLII enriched with HA by varying the biomacromolecule concentration and characterised it for degradation, stability and swelling properties. The WJ-MSC was then encapsulated in the hydrogel system to guide the cell differentiation into NP-like cells. Results: We successfully fabricated COLII hydrogel (2 mg/ml) and HA 10 mg/ml at a weight ratio of HA and COLII at 1:9 and 4.5:9, and both hydrogels physically maintained their 3D sphere-shaped structure after complete gelation. The higher composition of HA in the hydrogel system indicated a higher water intake capacity in the hydrogel with a higher amount of HA. All hydrogels showed over 60% hydrolytic stability over a month. The hydrogel showed an increase in degradation on day 14. The hWJ-MSCs encapsulated in hydrogel showed a round morphology shape that was homogenously distributed within the hydrogel of both groups. The viability study indicated a higher cell growth of hWJ-MSCs encapsulated in all hydrogel groups until day 14. Discussion: Overall, our findings demonstrate that HA/COLII hydrogel provides an optimal swelling capacity, stability, degradability, and non-cytotoxic, thus mimics the NP microenvironment in guiding hWJ-MSCs towards NP phenotype, which is potentially used as an advanced cell delivery system for intervertebral disc regeneration.