Beyond bioactivity: Chitosan macromolecular coatings on titanium surfaces drive osseointegration and immune suppression through targeted epigenetic regulation

Articles in Press

Document Type : Original Article

Authors

1 Department of Prosthodontics and Crown & Bridge, Government Dental College and Hospital, Cuddalore District, The Tamilnadu Dr. M.G.R. Medical University, Tamilnadu, India

2 Department of Prosthodontics and Crown & Bridge, Government Dental College and Hospital, Cuddalore District, The Tamilnadu Dr. M.G.R. Medical University, Tamilnadu

3 Department of Prosthodontics and Crown & Bridge, Government Dental College and Hospital, Cuddalore District, The Tamilnadu Dr. M.G.R. Medical University Tamilnadu

4 Department of Dentistry, Vinayaka Mission’s Medical College and Hospital, Vinayaka Mission’s Research Foundation (DU), Karaikal, Puducherry, India

5 Department of Periodontology, Government Dental College and Hospital, Cuddalore District, TheTamilnadu Dr. M.G.R. Medical University, Tamilnadu, India

10.22038/ijbms.2026.92524.19981

Abstract

Objective(s): To address titanium (Ti) implant failures caused by inadequate osseointegration and persistent inflammation by developing a novel dual-action coating. This coating utilizes a chitosan (CH) matrix to deliver epigenetic pharmaceuticals, 5-azacytidine (AZ) and trichostatin A (TR), onto Ti surfaces (AZ/TR-CH@TI).
Materials and Methods: Coating morphology and successful drug integration were validated via FTIR and SEM. Drug release kinetics were evaluated in physiological (pH 7.4) and inflammatory (pH 5.5) conditions over 48 hr. In vitro assessments utilizing MG63 osteoblast-like cells evaluated biocompatibility, anti-inflammatory responses, and osteogenic differentiation using real-time gene expression analysis, functional assays (alkaline phosphatase, Alizarin red), and immunofluorescence. 
Results: The composite exhibited an intelligent, pH-responsive controlled drug release. AZ/TR-CH@TI significantly enhanced biocompatibility, achieving 124.6% cell proliferation and 89.3% wound closure compared to uncoated controls. Gene expression analysis demonstrated potent anti-inflammatory effects, with TNF-α and IL-6 reduced to 0.31- and 0.35-fold, respectively. Concurrently, it augmented osteogenesis, up-regulating RUNX2 (2.60-fold), BMP2 (4.87-fold), and type-1 collagen (4.15-fold). Assays unequivocally validated comprehensive osteogenic differentiation and significant mineralization.
Conclusion: This macromolecular epigenetic drug-loaded CH coating effectively mitigates inflammation while simultaneously stimulating bone formation. The AZ/TR-CH@TI system presents a highly promising therapeutic approach to improve Ti osseointegration for clinical orthopaedic and dental applications.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 02 June 2026

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