A promising therapeutic biomaterial: CHX@ZnO-HA/PSSS nanocomposites enable pH-Dependent infection eradication and bone regeneration in osteomyelitis

Objectives: Osteomyelitis is a considerable clinical problem, necessitating multifunctional biomaterials that can concurrently manage infection and facilitate bone tissue regeneration. In this study, a chlorhexidine-loaded zinc oxide-hydroxyapatite/poly(sodium 4-styrene sulfonate) (CHX@ZnO-HA/PSSS) nanocomposite for possible therapeutic scaffold applications was manufactured and characterized. Methods: the MTT assay, dual acridine orange and ethidium bromide staining, scratch assays, and real-time polymerase chain reaction analysis of osteogenic markers (BMP2, RUNX2, osteocalcin, alkaline phosphatase, and type 1 collagen). Results: Characterization tests demonstrated the effective incorporation of the amorphous PSSS/CHX layer onto the crystalline ZnO-HA framework. Studies using SBF indicated the time-dependent bioactivity, characterized by the development of a dense, bone-like apatite layer by day 7. Drug release analysis indicated a biphasic, sustained pattern, achieving 40% cumulative release of CHX over 24 h at pH 7.4, regulated by Fickian transport kinetics. Biological assays demonstrated that the CHX@ZnO-HA/PSSS composite markedly improved cell survival (97%), accelerated wound closure in scratch tests, and upregulated essential osteogenic genes relative to the untreated progenitor control group. Conclusion: osteogenic potential. These findings show that the nanocomposite is a promising, multifunctional biomaterial for localized bone infection treatment and osseointegration enhancement.