Multifunctional Copper-Containing Carboxymethyl Chitosan/Alginate Scaffolds for Eradicating Clinical Bacterial Infection and Promoting Bone Formation

Abstract

Repairing infected bone defects relies on a scaffold that can not only fill the defects to promote bone formation but also kill clinically present bacterial pathogens such as Staphylococcus aureus (S. aureus). To meet this demand, here, we develop a new copper (Cu) containing natural polymeric scaffold with a full potential for repairing infected bone defects. Instead of directly adding antibacterial Cu2+ ions to the polymer mixtures, which caused uncontrolled polymer cross-linking, we added Cu nanoparticles to the mixture of anionic carboxymethyl chitosan (CMC) and alginate (Alg). Then, the Cu2+ ions released from the Cu nanoparticles gradually cross-linked the polymer mixtures, which was further turned into a scaffold (CMC/Alg/Cu) with an interconnected porous structure by freeze-drying. We found that the CMC/Alg/Cu scaffolds showed significantly improved capabilities of osteogenesis and killing clinical bacteria compared to CMC/Alg scaffolds fabricated by the same procedure but without adding Cu nanoparticles. Specifically, in vitro studies showed that the CMC/Alg/Cu scaffolds with excellent biocompatibility could enhance preosteoblastic cell adhesion by upregulating the expression level of adhesion-related genes (focal adhesion kinase (FAK), paxillin (PXN), and vinculin (VCL)), promoting osteogenic differentiation and mineralization by upregulating the osteogenesis-related gene expression and extracellular calcium deposition. In vivo studies further demonstrated that CMC/Alg/Cu scaffolds could induce the formation of vascularized new bone tissue in 4 weeks while avoiding clinical bacterial infection even when the implantation sites were challenged with the clinically collected S. aureus bacteria. This work represents a facile and innovative approach to the fabrication of Cu containing polymer scaffolds that can potentially be used to repair infected bone defects.

Calcium silicate bioactive ceramics induce osteogenesis through oncostatin M

“…Bone defects caused by trauma, tumor, and osteomyelitis have prompted the use of bone regeneration biomaterials [ [1] , [2] , [3] , [4] , [5] , [6] ]. Biomaterials for the regeneration of bone defects have rapidly developed from pure biological inert materials to materials that can stimulate osteoblast, osteoclast, and other specific cell responses at the molecular level [ 7 ].…”

Preparation and biological characterization of the mixture of poly(lactic-co-glycolic acid)/chitosan/Ag nanoparticles for periodontal tissue engineering

“…Thus, by mixing different materials characterized by different properties, such as natural polymers with inorganic materials or synthetic polymers, numerous research groups have strived to design and fabricate periodontal materials for GTR/GBR with the requisite features and properties. [10][11][12] Dental plaque biofilm is considered as the initial symptom of a periodontal disease. 13 The key to successful treatment of a periodontal disease is the effective control of the dental plaque.…”

Zero-Dimensional Carbon Dots Enhance Bone Regeneration, Osteosarcoma Ablation, and Clinical Bacterial Eradication

“…9,10 Moreover, CS has notable biofunctions, including antimicrobial, antifungal, and antioxidant activities. 11–13 nHA constitutes 50–70% of human bone and is also histocompatible and osteoinductive. 14 Hence, CS and nHA composites are appropriate candidates for basic bone repair scaffolds.…”