Keratin biomaterials with high molecular weights were intensively investigated but few are marketed due to complex methods of extraction and preparation and limited understanding of their influence on cells behavior. In this context the aim of this research was to elucidate decisive molecular factors for skin homeostasis restoration induced by two low molecular weight keratin hydrolysates extracted and conditioned through a simple and green method. Two keratin hydrolysates with molecular weights of 3758 and 12,400 Da were physico-chemically characterized and their structure was assessed by circular dichroism (CD) and FTIR spectroscopy in view of bioactive potential identification. Other investigations were focused on several molecular factors: α1, α2 and β1 integrin mediated signals, cell cycle progression in pro-inflammatory conditions (TNFα/LPS stimulated keratinocytes and fibroblasts) and ICAM-1/VCAM-1 inhibition in human vascular endothelial cells. Flow cytometry techniques demonstrated a distinctive pattern of efficacy: keratin hydrolysates over-expressed α1 and α2 subunits, responsible for tight bounds between fibroblasts and collagen or laminin 1; both actives stimulated the epidermal turn-over and inhibited VCAM over-expression in pro-inflammatory conditions associated with bacterial infections. Our results offer mechanistic insights in wound healing signaling factors modulated by the two low molecular weight keratin hydrolysates which still preserve bioactive secondary structure.

Osteoarthritis (OA) as a multi-factorial disease that features interrelated mechanisms (senescence/ apoptosis, proliferation, decreased synthesis of matrix proteins, activation of degrading enzymes, inflammation) and a diversity of cells involved in bone and cartilage metabolism: chondrocytes, osteoblasts, osteoclasts etc. A complete pharmaceutical solution remains an unsolved question in this interdisciplinary field of research.We focused our approach on osteoarthritic primary chondrocytes HC-OA (Cell Application), exploring on this primary cell line the small sea fish extract's potential to improve the proliferation rate and to stop the cytokines pro-inflammatory signaling. Previous research results have shown an important therapeutic potential of the small sea fish extract, restoring the intrinsic functionality of the cartilage through its correlative effects: antioxidant and anti-inflammatory action, stimulatory activity of cell proliferation and matriceal proteins homeostasis. In the context of pro-inflammatory and degradative stimulation with IL1β, the small sea fish extract prove a counteracting "in vitro" effect, restoring the proliferative capacity of HC-OA cells and inhibiting the IL8 release, with implication in several cartilage degradation pathways: MMP13 activation, neutrophils' accumulation, synovium leucocytes activation, as well as the hypertrophic and differentiation processes of chondrocytes.

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