Peek@ZIF-8(CEL) as a Novel Bone Implant for Large Defect Repair and Enhanced Bone Healing via a Long-Term Stable Bioactive Releaser.

The repair of large bone defects poses a significant challenge in orthopedics. Polyetheretherketone (PEEK) is a promising bone substitute, while it suffers a lack of bioactivity. Although several studies have been performed to further improve the bioactivities of PEEK by various surface modifications, PEEK offering long-term, multifaceted biofunctionalities remains still desired. In this study, we introduced metal-organic frameworks (MOFs), specifically ZIF-8 loaded with celecoxib (ZIF-8(CEL)), onto the PEEK surface through dopamine adhesion. The resulting PEEK@ZIF-8(CEL) aims to achieve long-term stable release of Zn ions and CEL for enhanced bone integration. Material characterization and biological experiments confirmed the successful integration of ZIF-8(CEL) onto PEEK and its positive biomedical effects, including creating a positive bone immunological environment and promoting bone growth. This study demonstrates the potential of PEEK@ZIF-8(CEL) as a novel repair material for large bone defects, offering a promising alternative in orthopedic applications.

Vascular endothelial cellular mechanics under hyperglycemia and its role in tissue regeneration.

Diabetes is one of the most prevalent diseases worldwide. The tissue regeneration of diabetes patients is known to be rather tricky as the result of vascular dysfunction, and this leads to various clinical complications including diabetic foot ulcers. The vascular endothelial cells, which compactly line the inner surface of blood vessels, are responsible for the growth and maintenance of blood vessels and play an essential role in tissue regeneration. Although the mechanical properties of cells are generally known to be regulated by physiological/pathological conditions, few studies have been performed to investigate vascular endothelial cellular mechanics under hyperglycemia and the biological functions related to tissue regeneration. In this study, we conduct a systematic investigation of this issue. The results suggested that the stiffness of human umbilical vein endothelial cells (HUVECs) can be significantly regulated by the glucose concentration, subsequently, leading to significant alterations in cell migration and proliferation capabilities that are closely related to tissue regeneration. The rearrangement of the cytoskeleton induced by hyperglycemia through Cdc42 was found to be one of the pathways for the alteration of the cell stiffness and the subsequent cell dysfunctions. Therefore, we suggested that the inhibition of Cdc42 might be a promising strategy to facilitate various tissue regeneration for diabetes patients.

The development of novel multifunctional drug system 7,8-DHF@ZIF-8 and its potential application in bone defect healing.

Physical exercise has long been considered an essential regulator of bone formation. Recent studies have shown that brain-derived neurotrophic factor (BDNF) is an important cytokine released during physical exercise to promote osteogenic differentiation and facilitate the bone defect healing process. In this study, we developed a multifunctional system 7,8-DHF@ZIF-8, which combines the superior osteogenesis and angiogenesis properties of ZIF-8 and the unique capability of 7,8-DHF to mimic the function of BDNF to compensate for the routine physical exercise missed during the bone defect period. Various material characterizations were performed to confirm the successful synthesis of 7,8-DHF@ZIF-8. Drug release experiments suggested that 7,8-DHF@ZIF-8 could achieve slow diffusive release under physiological conditions within seven days. In vitro cell experiments indicated that low concentrations of ZIF-8 and 7,8-DHF@ZIF-8 could significantly promote the proliferation of MC3T3-E1 cells. Moreover, as proved by RT-QPCR analysis, incorporating 7,8-DHF into ZIF-8 could further enhance osteogenesis and angiogenesis-related gene expression. Therefore, we believe that the multifunctional drug system 7,8-DHF@ZIF-8 should have promising applications to facilitate bone defect healing.

Strontium-modified porous polyetheretherketone with the triple function of osteogenesis, angiogenesis, and anti-inflammatory for bone grafting.

Polyetheretherketone (PEEK) is a potential bone repair material because of its stable chemical and good mechanical properties. However, the biological inertness of PEEK limits its clinical application. Sr2+ has multi biological functions, including promoting bone formation and blood vessel regeneration and inhibiting inflammation. In this paper, PEEK was modified with Sr2+ with the purpose to construct PEEK bone graft material with triple functions of osteogenesis, angiogenesis, and anti-inflammatory. The results showed that Sr-modified PEEK could stably release Sr2+ for a long time in the PBS solution, and indeed could promote the proliferation and differentiation of osteoblasts, promote angiogenesis, and inhibit inflammation. Therefore, it is believed that this multifunctional PEEK with Sr2+ should show great promise for clinical applications in bone repair.

Surface Modification of Poly(ether ether ketone) by Simple Chemical Grafting of Strontium Chondroitin Sulfate to Improve its Anti-Inflammation, Angiogenesis, Osteogenic Properties.

Besides inducing osteogenic differentiation, the surface modification of poly(ether ether ketone) (PEEK) is highly expected to improve its angiogenic activity and reduce the inflammatory response in the surrounding tissue. Herein, strontium chondroitin sulfate is first attempted to be introduced into the surface of sulfonated PEEK (SPEEK-CS@Sr) based on the Schiff base reaction between PEEK and ethylenediamine (EDA) and the amidation reaction between EDA and chondroitin sulfate (CS). The surface characteristics of SPEEK-CS@Sr implant are systematically investigated, and its biological properties in vitro and in vivo are also evaluated. The results show that the surface of SPEEK-CS@Sr implant exhibits a 3D microporous structure and good hydrophilicity, and can steadily release Sr ions. Importantly, the SPEEK-CS@Sr not only displays excellent biocompatibility, but also can remarkably promote cell adhesion and spread, improve osteogenic activity and angiogenic activity, and reduce the inflammatory response compared to the original PEEK. Therefore, this study presents the surface modification of PEEK material by simple chemical grafting of strontium chondroitin sulfate to improve its angiogenesis, anti-inflammation, and osteogenic properties, and the as-fabricated SPEEK-CS@Sr has the potential to serve as a promising orthopedic implant in bone tissue engineering.

A ZIF-8-based multifunctional intelligent drug release system for chronic osteomyelitis.

Chronic osteomyelitis (COM) is an inflammatory bone disease caused by bacterial infection. Conventional treatment with antibiotics is prone to resistance and other side effects, and it is ineffective against inflammation caused by infection and bone loss. To treat COM comprehensively, based on the acidic microenvironment of osteomyelitis, we used ZIF-8 and celecoxib to construct a multifunctional intelligent drug release system with pH response effect, named CEL@ZIF-8. Material characterization revealed that celecoxib is successfully loaded into ZIF-8. Ion release and drug release experiments indicated that CEL@ZIF-8 can respond well to the pH and intelligently control the release of ions and drugs. Antibacterial assays manifested that CEL@ZIF-8 is able to inhibit the growth of bacteria significantly. In vitro cell experiments demonstrated that CEL@ZIF-8 can significantly up-regulate the expression of osteogenesis-related cytokines and down-regulate the levels of inflammatory factors. Studies verify that the novel drug release system possesses multiple functions: antibacterial, osteogenesis, anti-inflammatory and intelligent release, suggesting a tremendous clinical promise for the treatment of COM.

An Mg-MOFs based multifunctional medicine for the treatment of osteoporotic pain.

Bone pain is the primary problem for patients with osteoporosis. Ketoprofen is clinically used to treat osteoporotic pain, while long-term oral administration of ketoprofen can cause some side effects. In addition, osteoporosis is also accompanied by bone mass loss and inflammation. In this study, we designed a multifunctional drug (Ket@Mg-MOF-74) adopted Mg-MOF-74 to load ketoprofen to treat osteoporotic pain, bone loss and inflammation comprehensively. Mg-MOF-74 was prepared, and the physicochemical characterization proved that it had excellent physical and chemical stability. Ket@Mg-MOF-74 was synthesized by post-synthetic modification method and a high loading rate of ketoprofen was confirmed. Drug release and ion release experiments indicated Ket@Mg-MOF-74 had a good controlled release of ketoprofen and Mg in solution. Cell experiments in vitro proved the compound drug could significantly reduce the expression of pain-related genes of cyclooxygenase 2 (COX2), obviously up-regulated the expression of osteogenic cytokines and remarkably down-regulated the secretion of pro-inflammatory factors. Therefore, Ket@Mg-MOF-74 is believed a promising painkiller for osteoporotic bone pain, with the function of anti-inflammatory and promoting bone formation.

Strontium Laminarin polysaccharide modulates osteogenesis-angiogenesis for bone regeneration.

Bone regeneration and repair has become one of the major clinical challenges worldwide and it involves multiple processes including inflammation, angiogenesis and osteogenesis. In this study, we synthesized strontium Laminarin polysaccharide (LP-Sr), a novel polysaccharide-metal complex that should have therapeutic effects on modulating osteogenesis and angiogenesis. The structure and composition of the as-fabricated LP-Sr were analyzed by EDS, XRD, FITR, 1H NMR, HPLC, etc. The results indicate that we successfully synthesized this novel polysaccharide complex. Moreover, we evaluated the biomedical potential of this complex in promoting osteogenesis and angiogenesis by cell proliferation assay, ALP staining, immunofluorescent staining of CD31 and reverse transcription polymerase chain reaction (RT-PCR). The biological experiment results show that LP-Sr can effectively promote proliferation and increase the expression of VEGF and EGFL6 in HUVECs and significantly up-regulate the expression of Col1α1 and OCN in MC3T3-E1. Besides, it is suggested that LP-Sr has positive effects on the suppression of pro-inflammatory factor IL6 in both HUVECs and MC3T3-E1. Moreover, the osteogenic and angiogenic markers, i.e. alkaline phosphatase (ALP) and CD31, exhibited high expression in LP-Sr group. Hence, we believe that LP-Sr should be a promising and novel polysaccharide complex in modulating osteogenesis-angiogenesis for bone regeneration.

In situ fabrication of a composite hydrogel with tunable mechanical properties for cartilage tissue engineering.

A composite hydrogel with tunable mechanical properties has been fabricated and characterized in this study. We investigated its swelling degree, morphology, structure and thermal stability. Moreover, the effect of strontium chloride concentration on both the dynamic rheology and nanomechanical properties of the composite hydrogels was confirmed in this work. To eliminate the viscoelastic influences of hydrogels during nanomechanical tests, we first analyzed the elastic modulus of strontium alginate (Alg-Sr) and strontium alginate/chondroitin sulfate (Alg/CS-Sr) hydrogels via atomic force microscopy (AFM) using the rate-jump method. Chondrocytes were cultured with the Alg-Sr and Alg/CS-Sr hydrogels respectively. Cell viability assay reveals that the Alg/CS-Sr hydrogel possesses good cytocompatibility. Flow cytometry, qPCR and western blotting analysis suggest that the Alg/CS-Sr hydrogel exerts a positive effect on the inhibition of apoptosis and may exert anti-inflammatory effects in articular cartilage related applications. Furthermore, the preliminary in vivo study shows that the Alg/CS-Sr composite hydrogel facilitates the repair of cartilage in rabbit cartilage defect. Taken together, it is indicated that the Alg/CS-Sr composite hydrogel might be a promising scaffold to promote the repair of cartilage defects.