Exploring the Osteoinductive Potential of Bacterial Pyomelanin Derived from Pseudomonas aeruginosa in a Human...

Alkaptonuria (AKU) is a genetically determined disease associated with disorders of tyrosine metabolism. In AKU, the deposition of homogentisic acid polymers contributes to the pathological ossification of cartilage tissue. The controlled use of biomimetics similar to deposits observed in cartilage during AKU potentially may serve the development of new bone regeneration therapy based on the activation of osteoblasts. The proposed biomimetic is pyomelanin (PyoM), a polymeric biomacromolecule synthesized by Pseudomonas aeruginosa. This work presents comprehensive data on the osteoinductive, pro-regenerative, and antibacterial properties, as well as the cytocompatibility, of water-soluble (PyoM_sol) or water-insoluble (PyoM_insol) PyoM. Both variants of PyoM support osteoinductive processes as well as the maturation of osteoblasts in cell cultures in vitro due to the upregulation of bone-formation markers, osteocalcin (OC), and alkaline phosphatase (ALP). Furthermore, the cytokines involved in these processes were elevated in cell cultures of osteoblasts exposed to PyoM: tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10. The PyoM variants are cytocompatible in a wide concentration range and limit the doxorubicin-induced apoptosis of osteoblasts. This cytoprotective PyoM activity is correlated with an increased migration of osteoblasts. Moreover, PyoM_sol and PyoM_insol exhibit antibacterial activity against staphylococci isolated from infected bones. The osteoinductive, pro-regenerative, and antiapoptotic effects achieved through PyoM stimulation prompt the development of new biocomposites modified with this bacterial biopolymer for medical use.