As the most common cause of low back pain, the cascade of intervertebral disc (IVD) degeneration is initiated by the disappearance of notochordal cells and progressive loss of proteoglycan (PG). Limited nutrient supply in the avascular disc environment restricts the production of ATP which is an essential energy source for cell survival and function such as PG biosynthesis. The objective of this study was to examine ATP level and PG production of porcine IVD cells under prolonged exposure to hypoxia with physiological glucose concentrations. The results showed notochordal NP and AF cells responded differently to changes of oxygen and glucose. Metabolic activities (including PG production) of IVD cells are restricted under the in-vivo nutrient conditions while NP notochordal cells are likely to be more vulnerable to reduced nutrition supply. Moreover, provision of energy, together or not with genetic regulation, may govern PG production in the IVD under restricted nutrient supply. Therefore, maintaining essential levels of nutrients may reduce the loss of notochordal cells and PG in the IVD. This study provides a new insight into the metabolism of IVD cells under nutrient deprivation and the information for developing treatment strategies for disc degeneration.

Damage caused by disease or trauma often leads to multi-tissue damage which is both painful and expensive for the patient. Despite the common occurrence of such injuries, reconstruction can be incredibly challenging and often may focus on a single tissue, which has been damaged to a greater extent, rather than the environment as a whole. Tissue engineering offers an approach to encourage repair, replacement, and regeneration using scaffolds, biomaterials and bioactive factors. However, there are many advantages to creating a combined scaffold fabrication method approach that incorporates the treatment and regeneration of multiple tissue types simultaneously. This review provides a guide to combining multiple tissue-engineered scaffold fabrication methods to span several tissue types concurrently. Briefly, a background in the healing and composition of typical tissues targeted in scaffold fabrication is provided. Then, common tissue-engineered scaffold fabrication methods are highlighted, specifically focusing on porosity, mechanical integrity, and practicality for clinical application. Finally, an overview of commonly used scaffold biomaterials and additives is provided, and current research in combining multiple scaffold fabrication techniques is discussed. Overall, this review will serve to bridge the critical gap in knowledge pertaining to combining different fabrication methods for tissue regeneration without disrupting structural integrity and biomaterial properties.

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Hydrogels provide a promising method for the targeted delivery of protein drugs. Loading the protein drug into the hydrogel free volume can be challenging due to limited quantities of the drug (e.g., growth factor) and complex physicochemical properties of the hydrogel. Here, we investigated both passive and active loading of the heteropolysaccharide hydrogel pectin. Passive loading of glass phase pectin films was evaluated by contact angles and fractional thickness of the pectin films. Four pectin sources demonstrated mean contact angles of 88° with water and 122° with pleural fluid (p < 0.05). Slow kinetics and evaporative losses precluded passive loading. In contrast, active loading of the translucent pectin films was evaluated with the colorimetric tracer methylene blue. Active loading parameters were systematically varied and recorded at 500 points/s. The distribution of the tracer was evaluated by image morphometry. Active loading of the tracer into the pectin films required the optimization of probe velocity, compression force, and contact time. We conclude that active loading using pectin-specific conditions is required for the efficient embedding of low viscosity liquids into pectin hydrogels.