Revolutionizing fracture fixation in diabetic and non-diabetic rats: High mobility group box 1-based coating for enhanced osseointegration

Alexandra Arteaga; Claudia Cristina Biguetti; BhuvanaLakkasetter Chandrashekar; Javier La Fontaine; Danieli C Rodrigues

doi:10.1016/j.bone.2023.116917

Revolutionizing fracture fixation in diabetic and non-diabetic rats: High mobility group box 1-based coating for enhanced osseointegration

Bone. 2023 Dec:177:116917. doi: 10.1016/j.bone.2023.116917. Epub 2023 Sep 20.

Authors

Alexandra Arteaga¹, Claudia Cristina Biguetti², BhuvanaLakkasetter Chandrashekar¹, Javier La Fontaine², Danieli C Rodrigues³

Affiliations

¹ Department of Bioengineering, The University of Texas at Dallas, Richardson, TX, USA.
² Department of Surgery and Biomechanics, School of Podiatric Medicine, The University of Texas Rio Grande Valley, Harlingen, TX, USA.
³ Department of Bioengineering, The University of Texas at Dallas, Richardson, TX, USA. Electronic address: danieli@utdallas.edu.

PMID: 37739297
DOI: 10.1016/j.bone.2023.116917

Abstract

Chronic inflammation and hyperglycemia in diabetic patients increase the risk of implant failure and impaired fracture healing. We previously developed and characterized a titanium (Ti) coating strategy using an imidazolium-based ionic liquid (IonL) with a fully reduced, non-oxidizable High Mobility Group Box 1 (HMGB1) isoform (Ti-IonL-HMGB1) to immunomodulate tissue healing. In this study, we used an open reduction fracture fixation (ORIF) model in non-diabetic (ND) and diabetic (D) rats to further investigate the effectiveness of this Ti-IonL-HMGB1 coating on orthopedic applications. Ninety male Lewis rats (12-15 weeks) were divided into D (n = 45) and ND (n = 45) groups that were distributed into three subgroups based on the type of local treatment received: Ti (uncoated Ti), Ti-IonL, and Ti-IonL-HMGB1 implants. Fracture healing and osseointegration were evaluated using microtomographic, histological, and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), Runt-related transcription factor 2 (RUNX2), and HMGB1 markers at 2, 10, and 21 days post-ORIF. Scanning Electron Microscopy verified the coating stability after placement. Microtomographic and histological analysis demonstrated increased fracture healing and osseointegration for ND rats in all treatment groups at 10 days, with impaired healing for D rats. Immunohistochemical analysis exhibited elevated PCNA+ and RUNX2+ cells for D animals treated with Ti-IonL-HMGB1 at 21 days compared to all other groups. The immunohistochemical marker HMGB1 was elevated at all time points for D animals in comparison to ND animals, yet was lowered for D tissues near the Ti-IonL-HMGB1 treated implant. Improved osseous healing was demonstrated in D animals with Ti-IonL-HMGB1 treatment by 21 days, compared to D animals with other treatments. To the best of our knowledge, this is the first study analyzing Ti-IonL-HMGB1 implantation in an injury site through ORIF procedures in ND and D rats. This surface approach has potential for improving implanted biomaterials in diabetic environments.

Keywords: HMGB1; Immunomodulation; Ionic liquids; Orthopedic implants; Osseointegration; Rodent models; Titanium.