4.8 Article

Nutrient Element Decorated Polyetheretherketone Implants Steer Mitochondrial Dynamics for Boosted Diabetic Osseointegration

Journal

ADVANCED SCIENCE
Volume 8, Issue 20, Pages -

Publisher

WILEY
DOI: 10.1002/advs.202101778

Keywords

mitochondrial dynamics; nutrient element; orthopedic implant; osseointegration; polyetheretherketone

Funding

  1. National Natural Science Foundation of China [81870802, 81961160736, 81801848]
  2. Sichuan Science and Technology Program [2019YFS0356, 2018JZ0026, 2021YJ0049, 2019YJ0141]
  3. Chengdu International Science and Technology Cooperation Foundation [2017-GH02-00025-HZ, 2020-GH03-00005-HZ]
  4. State Key Laboratory of Polymer Materials Engineering [sklpme2019-2-05]
  5. Young Elite Scientist Sponsorship Program by CAST, Youth Science and Technology Academic Leader Training Program of (Sichuan University), Sichuan University-Luzhou City Special Funding for Strategic Cooperation [2020CDLZ-5]
  6. Sichuan University Postodoctoral Interdisciplinary Innovation
  7. Fundamental Research Funds for the Central Universities
  8. Hong Kong Scholar

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This study introduced a novel mitochondria-targeted orthopedic implant with Zn2+ and Sr2+ modulation capability for enhancing bone formation and osseointegration in diabetic patients. The implant demonstrated the ability to recuperate mitochondrial dynamic disequilibrium and dysfunction in hyperglycemic conditions, ultimately enhancing osteogenicity of osteoblasts. In vivo evaluations further confirmed that nutrient element coatings substantially augment bone remodeling and osseointegration.
As a chronic metabolic disease, diabetes mellitus (DM) creates a hyperglycemic micromilieu around implants, resulting inthe high complication and failure rate of implantation because of mitochondrial dysfunction in hyperglycemia. To address the daunting issue, the authors innovatively devised and developed mitochondria-targeted orthopedic implants consisted of nutrient element coatings and polyetheretherketone (PEEK). Dual nutrient elements, in the modality of ZnO and Sr(OH)(2), are assembled onto the sulfonated PEEK surface (Zn&Sr-SPEEK). The results indicate the synergistic liberation of Zn2+ and Sr2+ from coating massacres pathogenic bacteria and dramatically facilitates cyto-activity of osteoblasts upon the hyperglycemic niche. Intriguingly, Zn&Sr-SPEEK implants are demonstrated to have a robust ability to recuperate hyperglycemia-induced mitochondrial dynamic disequilibrium and dysfunction by means of Dynamin-related protein 1 (Drp1) gene down-regulation, mitochondrial membrane potential (MMP) resurgence, and reactive oxygen species (ROS) elimination, ultimately enhancing osteogenicity of osteoblasts. In vivo evaluations utilizing diabetic rat femoral/tibia defect model at 4 and 8 weeks further confirm that nutrient element coatings substantially augment bone remodeling and osseointegration. Altogether, this study not only reveals the importance of Zn2+ and Sr2+ modulation on mitochondrial dynamics that contributes to bone formation and osseointegration, but also provides a novel orthopedic implant for diabetic patients with mitochondrial modulation capability.

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