Bioinspired adhesive polydopamine-metal-organic framework functionalized 3D customized scaffolds with enhanced angiogenesis, immunomodulation, and osteogenesis for orbital bone reconstruction

• Published in: International journal of biological macromolecules 2025-01, Vol.284 (Pt 1), p.137968, Article 137968
• Main Authors: Shi, Jieliang, Liu, Zhirong, Ren, Xiaobin, Wang, Wei, Zhang, Haojie, Wang, Yuanli, Liu, Mingyue, Yao, Qingqing, Wu, Wencan
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Benzophenones; Bone Regeneration - drug effects; Deferoxamine - chemistry; Deferoxamine - pharmacology; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Immunomodulation; Immunomodulation - drug effects; Indoles - chemistry; Indoles - pharmacology; Metal-Organic Frameworks - chemistry; Metal-Organic Frameworks - pharmacology; Mice; Neovascularization, Physiologic - drug effects; Orbital bone reconstruction; Osteogenesis - drug effects; Polyethylene Glycols - chemistry; Polymers - chemistry; Rabbits; Tissue Engineering - methods; Tissue Scaffolds - chemistry
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.137968

Critical-sized orbital bone defects can lead to significant maxillofacial deformities and even eye movement disorders. The challenges associated with these defects, including their complicated structure, inadequate blood supply, and limited availability of progenitor cells that hinder successful repair. To overcome these issues, we developed a novel approach using computer numerical control (CNC) material reduction manufacturing technology to produce a customized polyetheretherketone (PEEK) scaffold that conforms to the specific shape of orbital bone defects. Deferoxamine (DFO) was in situ encapsulated into polydopamine-hybridized zeolitic imidazolate framework-8 (pZIF8-DFO) nanoparticles, which was subsequently adhered to the sulfonated PEEK (sPEEK) scaffold through polydopamine modification. This functionalization enhanced drug loading efficiency and imparted anti-inflammatory properties to the nanoparticle system. Our in vitro findings demonstrated that the sustained release of DFO from the sPEEK/pZIF8-DFO scaffolds extended over 14 days and significantly promoted angiogenesis and progenitor cell recruitment, as evidenced by increased expression of HIF-1α, VEGF, and SDF-1α expression in human umbilical vein endothelial cells (HUVECs). Moreover, sPEEK/pZIF8-DFO scaffolds exhibited superior immunomodulation and osteogenic differentiation capabilities on Raw 264.7 cells and rabbit bone marrow mesenchymal stem cells (rBMSCs), respectively. Most notably, our in vivo rabbit orbital bone defects revealed that sPEEK/pZIF8-DFO scaffolds resulted in a greater volume of new bone formation than on sPEEK and sPEEK/pZIF8 scaffolds, with partial bone connection to the sPEEK/pZIF8-DFO scaffolds. In summary, we develop a novel PEEK scaffold that combines enhanced angiogenesis, stem cell recruitment, immunomodulation, and osteogenic differentiation, showcasing its promising potential for orbital bone reconstruction. [Display omitted]