Chiara Schiraldi

Currently, chondroitin sulfate (CS) and hyaluronic acid (HA) pharma-grade forms are used for osteoarthritis (OA) management, CS as an oral formulations component, and HA as intra-articular injective medical devices. Recently, unsulfated chondroitin, obtained through biofermentative (BC) manufacturing, has been proposed for thermally stabilized injective preparation with HA. This study aimed to highlight the specific properties of two commercial injective medical devices, one based on HA/BC complexes and the other containing HA, extractive CS, and cyclodextrins, in order to provide valuable information for joint disease treatments. Their biophysical and biomechanical features were assayed; in addition, biological tests were performed on human pathological chondrocytes. Rheological measurements displayed similar behavior, with a slightly higher G′ for HA/BC, which also proved superior stability to the hyaluronidase attack. Both samples reduced the expression of specific OA-related biomarkers such as NF-kB, interleukin 6 (IL-6), and metalloprotease-13 (MMP-13). Moreover, HA/BC better ensured chondrocyte phenotype maintenance by up-regulating collagen type 2A1 (COLII) and aggrecan (AGN). Notwithstanding, the similarity of biomolecule components, the manufacturing process, raw materials characteristics, and specific concentration resulted in affecting the biomechanical and, more interestingly, the biochemical properties, suggesting potential better performances of HA/BC in joint disease treatment.

Lactobacillus rhamnosus is a homofermentative probiotic strain that was previously demonstrated to grow on lignocellulosic-derived raw materials and to convert glucose into L-lactic acid (LA) with yields that vary between 0.38 and 0.97 g/g. Lactic acid is a key platform chemical, largely applied in different biotechnological fields (spanning from the pharmaceutical to the food sector) and also as a building block for the production of biodegradable polymers. In the present study, grape stalks were evaluated as sources of fermentable sugars for the growth of L. rhamnosus IMC501 and for the production of LA, since millions of hectoliters of wine are produced every year worldwide, generating a huge amount of waste. Although grape stalks are quite recalcitrant, the combination of a steam explosion pre-treatment with optimized two-step hydrolysis and commercial enzymes (Cellic-CTec2) allowed us to obtain a cellulose conversion efficiency of about 37% and to develop small-scale 2 L batch fermentation processes. Results successfully demonstrate that L. rhamnosus IMC501 can tolerate biomass-derived inhibitors and grow on grape stalk hydrolysate without the need for additional sources of nitrogen or other nutritional elements, and that the strain can convert all glucose present in the medium into LA, reaching the maximal theoretical yield.