Urbaniak Mateusz M, Rudnicka Karolina, Płociński Przemysław, Chmiela Magdalena
Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, 12/16 Banacha St, 90-237 Łódź, Poland.
Department of Inorganic and Analytical Chemistry, Faculty of Chemistry, University of Lodz, 12 Tamka St, 91-403 Łódź, Poland.
Int J Mol Sci. 2024 Dec 14;25(24):13406. doi: 10.3390/ijms252413406.
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 . This work presents comprehensive data on the osteoinductive, pro-regenerative, and antibacterial properties, as well as the cytocompatibility, of water-soluble (PyoM) or water-insoluble (PyoM) 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 and PyoM 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.
黑尿症（AKU）是一种与酪氨酸代谢紊乱相关的遗传性疾病。在AKU中，尿黑酸聚合物的沉积会导致软骨组织病理性骨化。在AKU中，类似于软骨中观察到的沉积物的仿生材料的可控使用，可能有助于基于成骨细胞激活的新骨再生疗法的开发。所提出的仿生材料是焦黑素（PyoM），一种由……合成的聚合生物大分子。这项工作展示了关于水溶性（PyoM）或水不溶性（PyoM）PyoM的骨诱导、促再生和抗菌特性以及细胞相容性的全面数据。由于骨形成标志物骨钙素（OC）和碱性磷酸酶（ALP）的上调，PyoM的两种变体都支持骨诱导过程以及体外细胞培养中成骨细胞的成熟。此外，在暴露于PyoM的成骨细胞的细胞培养物中，参与这些过程的细胞因子水平升高：肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6和IL-10。PyoM变体在很宽的浓度范围内具有细胞相容性，并限制阿霉素诱导的成骨细胞凋亡。这种细胞保护作用与成骨细胞迁移增加相关。此外，PyoM和PyoM对从感染骨中分离出的葡萄球菌具有抗菌活性。通过PyoM刺激实现的骨诱导、促再生和抗凋亡作用促使开发用这种细菌生物聚合物改性的新型生物复合材料用于医学用途。
