Instructive cartilage regeneration modalities with advanced therapeutic implantations under abnormal conditions.

Instructive cartilage regeneration modalities with advanced therapeutic implantations under abnormal conditions

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.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/advs.202101778

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

https://doi.org/10.1016/j.bioactmat.2022.02.012

Exosome-functionalized magnesium-organic framework-based scaffolds with osteogenic, angiogenic and anti-inflammatory properties for accelerated bone regeneration

3D-printable chitosan/silk fibroin/cellulose nanoparticle scaffolds for bone regeneration via M2 macrophage polarization.

Marginal sealing around integral bilayer scaffolds for repairing osteochondral defects based on photocurable silk hydrogels.

Forming a stable anti-corrosion surface layer on magnesium (Mg) and its alloys has become a major challenge in developing a desirable degradable medical implant in bone. In this study, a porous MgO layer was first formed on Mg by plasma electrolytic oxidation (PEO), and then a Mg-Al layered double hydroxide (LDH) layer was prepared to seal the porous structure of the PEO layer (LDH-2h and LDH-12h) via hydrothermal treatment. The bilayer structure composite coating, which can effectively resist the penetration of surrounding media, is similar to plain Chinese tiles. The in vitro results revealed that compared with other coatings, the LDH-12h composite coating can reduce the release of Mg ions and induce a milder change in pH when immersed in phosphate-buffered saline (PBS). In vitro rat bone marrow stem cell (rBMSC) culture suggested that the LDH-12h composite coating is favorable for cell activity, proliferation and could improve the osteogenic activity of rBMSCs. A subcutaneous implantation test revealed that the as-prepared sample showed enhanced corrosion resistance and histocompatibility in vivo, especially in the LDH-12h group. Moreover, LDH-12h had the lowest rate of degradation and the closest combination with the new bone after being inserted into a rat femur for 12 weeks with no major organ dysfunction. In summary, the asprepared PEO/Mg-Al LDH composite coating is able to improve the corrosion resistance and biocompatibility of Mg and to enhance osteogenic activity in vivo, suggesting its promising prospects for orthopedic applications.

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Biocompatibility and bone regeneration of PEO/Mg-Al LDH-coated pure Mg: an in vitro and in vivo study

Copper peptide-incorporated 3D-printed silk-based scaffolds promote vascularized bone regeneration

Peri-implantitis is a typical pathological condition characterized by the destructive inflammation in the soft tissue and the progressive loss of supporting bones. As the current effective treatments and preventive measures are inconsistent and unpredictable, the use of biomaterials as carriers of bioactive ion coatings is a promising approach. However, the translation from lab to large-scale production and clinical applications is difficult due to a technology barrier. Determining the effective dosage of each ion to achieve an in vivo application of the in vitro screening is challenging. Here, we selected zinc and strontium ions to provide multiple effects on antibacterial activity and osteogenesis. The optimal coating with effective release concentrations of the two ions was obtained after the two-step screening from in vitro testing. The results showed that this type of in vivo bioactive ion usage leads to an enhanced osseointegration during the immediate implantation in a periodontitis-affected environment and prevents soft tissue inflammation and bone resorption in an inflammatory environment. The new biologically active ion screening method could verify the effectiveness of this clinical translation and its potential for large-scale production and could determine the effective dosage of each ion for a specific application.

The Translation from In Vitro Bioactive Ion Concentration Screening to In Vivo Application for Preventing Peri-implantitis.

Injectable hydrogels provide an effective strategy for minimally invasive treatment on irregular bony defects in the maxillofacial region. To improve the osteoinduction of gelatin methacrylate (GelMA), we fabricated a three-dimensional (3D) culture system based on the incorporation of magnesium ammonium phosphate hexahydrate (struvite) into GelMA. The optimal concentration of struvite was investigated using the struvite extracts, and 500 μg mL-1 was found to be the most suitable concentration for the osteogenesis of dental pulp stem cells (DPSCs) and angiogenesis of human umbilical vein endothelial cells (HUVECs). We prepared the GelMA composite (MgP) with 500 μg mL-1 struvite. Struvite did not affect the cross-linking of GelMA and released Mg2+ during degradation. The cell delivery system using MgP improved the laden-cell viability, upregulated the expression of osteogenic and angiogenic-differentiation-related genes, and promoted cell migration. Overall, the modifications made to the GelMA in this study improved osteoinduction and demonstrated great potential for application in vascularized bone tissue regeneration.

Xiaolin Wu

Papers

Marginal sealing around integral bilayer scaffolds for repairing osteochondral defects based on photocurable silk hydrogels.

Biocompatibility and bone regeneration of PEO/Mg-Al LDH-coated pure Mg: an in vitro and in vivo study

Copper peptide-incorporated 3D-printed silk-based scaffolds promote vascularized bone regeneration

The Translation from In Vitro Bioactive Ion Concentration Screening to In Vivo Application for Preventing Peri-implantitis.

Magnesium Ammonium Phosphate Composite Cell-Laden Hydrogel Promotes Osteogenesis and Angiogenesis In Vitro.