Surface bioactivation of Polyetheretherketone (PEEK) by magnesium chondroitin sulfate (MgCS) as orthopedic implants for reconstruction of skeletal defects.

Polyether-ether-ketone (PEEK) is clinically used as a bio-implant for the healing of skeletal defects. However, the osseointegration of clinical-sized bone grafts remains limited. In this study, surface-porous PEEK was created by using a sulfonation method and a metal-polysaccharide complex MgCS was introduced on the surface of sulfonated PEEK to form MgCS@SPEEK. The as-prepared MgCS@SPEEK was found to have a porous surface with good hydrophilicity and bioactivity. This was followed by an investigation into whether MgCS loaded onto sulfonated PEEK surfaces could promote osseointegration and angiogenesis. The in vitro results showed that MgCS@SPEEK had a positive effect on reducing the expression levels of inflammatory genes and promoting osteogenesis and angiogenesis-related genes expression levels. Furthermore, porous MgCS@SPEEK was implanted in critical-sized rat tibial defects for in vivo evaluation of osseointegration. The micro-computed tomography evaluation results revealed substantial bone formation at 4 and 8 weeks. Collectively, these findings indicate that MgCS@SPEEK could provide improved osseointegration and an attractive strategy for orthopaedic applications.

Surface modifications of titanium dental implants with strontium eucommia ulmoides to enhance osseointegration and suppress inflammation.

BACKGROUND: Titanium (Ti) is now widely used as implant material due to its excellent mechanical properties and superior biocompatibilities, while its inert bioactivities might lead to insufficient osseointegration, and limit its performance in dental applications. METHODS: We introduced a robust and simple approach of modifying titanium surfaces with polysaccharide complexes. Titanium samples were subjected to hydrothermal treatment to create a uniform porous structure on the surface, followed by coating with a bioinspired and self-assembly polydopamine layer. Strontium Eucommia Ulmoides Polysaccharide (EUP-Sr) complexes are then introduced to the polydopamine-coated porous titanium. Multiple morphological and physiochemical characterizations are employed for material evaluation, while cell proliferation and gene expression tests using macrophages, primary alveolar bone osteoblasts, and vascular endothelial cells are used to provide an overall insight into the functions of the product. The significances of statistical differences were analyzed using student's t-test. RESULTS: Microscopic and spectrometric characterizations confirmed that the Ti surface formed a porous structure with an adequate amount of EUP-Sr loading. The attachment was attributed to hydrogen bonding between the ubiquitous glycosidic linkage of the polysaccharide complex and the ring structure of polydopamine, yet the loaded EUP-Sr complex can be gradually released, consequently benefiting the neighboring microenvironment. Cell experiments showed no cytotoxicity of the material, and the product showed promising anti-inflammation, osseointegration, and angiogenesis properties, which were further confirmed by in vivo evaluations. CONCLUSION: We believe the EUP-Sr modified titanium implant is a promising candidate to be used in dental applications with notable osteoimmunomodulation and angiogenesis functions. And the novel technique proposed in this study would benefit the modification of metal/inorganic surfaces with polysaccharides for future research.

Hybrid composites with magnesium-containing glycosaminoglycans as a chondroconducive matrix for osteoarthritic cartilage repair.

The alteration of the extracellular matrix (ECM) homeostasis plays an important role in the development of osteoarthritis (OA). The pathological changes of OA are mainly manifested in the large reduction of components in ECM, like type II collagen and aggrecan, especially hyaluronic acid and chondroitin sulfate and often accompanied by inflammation. Rebuilding ECM and inhibiting inflammation may reverse OA progression. In this work, we developed new magnesium-containing glycosaminoglycans (Mg-GAGs), to create a positive ECM condition for promoting cartilage regeneration and alleviating OA. In vitro results suggested that the introduction of Mg-GAGs contributed to promoting chondrocyte proliferation and facilitated upregulating chondrogenic genes and suppressed inflammation-related factors. Moreover, Mg-GAGs exhibited positive effects on suppressing synovial inflammation, reducing chondrocyte apoptosis and preserving the subchondral bone in the ACLT-induced OA rabbit model. This study provides new insight into ECM-based therapeutic strategy and opens a new avenue for the development of novel OA treatment.

Strontium based Astragalus polysaccharides promote osteoblasts differentiation and mineralization.

Bone formation and repair represent a clinical challenge. In this work, we designed and synthesized strontium Astragalus polysaccharide (APS-Sr), a novel polysaccharide compound that should have therapeutic effects on both anti-inflammation and promoting bone formation. Using material characterization techniques, including SEM, FITR, XRD, etc., we verified the successful synthesis of this compound. Moreover, we examined the potential of this compound for promoting bone repair and inhibiting inflammatory response by cell proliferation assay, ALP and Alizarin Red staining experiments and RT-qPCR. The biological experiment results showed that APS-Sr can effectively inhibit inflammatory factors, promote osteogenic differentiation and up-regulate the bone growth factors. It is therefore believed that APS-Sr should be a promising polysaccharide compound in bone-related biomedical applications.

Chondroitin sulfate zinc with antibacterial properties and anti-inflammatory effects for skin wound healing.

A chondroitin sulfate zinc (CSZn) complex was prepared by an ion-exchange method. The purified product was characterized by energy-dispersive X-ray spectroscopy, high-performance chromatography, elemental analysis, Fourier transform infrared spectroscopy, inductively coupled mass spectrometry, and nuclear magnetic resonance spectroscopy. The CSZn demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus and satisfied MTT cell viability (NIH3T3 fibroblasts) at ≤50 µg/mL. RT-PCR demonstrated significant promotion by CSZn of fibroblast growth factor beta (ß-FGF), collagen III (COLIIIα1), vascular endothelial growth factor (VEGF) and reduction of cytokines IL-6, IL-1ß & TNF-alpha. An in vivo rat full-thickness wound healing model demonstrated significant wound healing of CSZn relative to controls of saline treatment, zinc chloride treatment and chondroitin treatment. CSZn has demonstrated promising antibacterial and wound healing properties making it deserving of consideration for more advanced wound healing applications.

Chitosan-strontium chondroitin sulfate scaffolds for reconstruction of bone defects in aged rats.

Bone defects caused by trauma have become increasingly common in aged populations. Clinically, because of the relatively decreased bone healing capacity compared with the youth adults, bone defect repair in the elderly remains challenging. The development of effective biomaterials targeted at bone defects in the elderly is a key component of bone-tissue engineering strategies. However, little attention has been paid to bone regeneration in the elderly. Here, we developed a new scaffold chitosan-Strontium chondroitin sulfate (CH-SrCS) and evaluated its effect on improving bone regeneration. We find that the CH-SrCS scaffold displayed positive effects on downregulation of inflammation and osteoclastogenesis related mRNA expressions while demonstrating a significant increase in the expression level of BMP2. Finally, we show that the bone defects healing effects as assessed using an aged rats' bone defects model. Ultimately, this work also provides insights into the design of effective biomaterials targeted at bone defects in the elderly.

Synthesis of carboxymethyl chitosan-strontium complex and its therapeutic effects on relieving osteoarthritis.

Osteoarthritis (OA) is an age-related joint disorder and one of the leading causes of physical disability. In this study, we designed and synthesized a new polysaccharide complex, carboxymethyl chitosan strontium (CMCS-Sr), which is believed to have positive effects on relieving OA. The synthesized CMCS-Sr was structurally verified by SEM, EDS, FTIR, etc. The therapeutic effects of CMCS-Sr were evaluated using various biological experiments. The cell viability and apoptosis results reveal that CMCS-Sr can significantly promote the proliferation and suppress OA chondrocytes apoptosis in vitro. The immunofluorescence staining results suggest that CMCS-Sr facilitates the promotion of the secretion of Type II collagen (Col-II). The transcriptomic results support the observed positive effects of CMCS-Sr on inhibiting chondrocytes apoptosis and alleviating inflammatory reactions. Moreover, animal study demonstrates that CMCS-Sr effectively reduced articular cartilage damage and subchondral bone degradation. Therefore, we propose the use of CMCS-Sr as a promising candidate for relieving OA.

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.

Metformin Hydrochloride Encapsulation by Alginate Strontium Hydrogel for Cartilage Regeneration by Reliving Cellular Senescence.

Cartilage lesion is a common tissue defect and is challenging in clinical practice. Trauma-induced cellular senescence could decrease the chondrocyte capability of maintaining cartilage tissue regeneration. A previous investigation showed that, by controlling the cellular senescence, the cartilage regeneration can be significantly accelerated. Based on this finding, we design a novel hydrogel, Alg/MH-Sr, that combines metformin, an established drug for inhibiting senescence, and strontium, an effective anti-inflammatory material for cartilage tissue engineering. A RT-PCR test suggests the significant inhibitory effect of the hydrogel on senescent, apoptotic, oxidative, and inflammatory genes' expression. Histological examinations demonstrate that the Alg/MH-Sr hydrogel accelerated cartilage repairment, and chondrocyte senescence was significantly inhibited. Our study demonstrates that the Alg/MH-Sr hydrogel is effective for cartilage defect treatment and provides a new clue in accelerating tissue repairment by inhibiting the senescence of cells and tissues.

Fabrication of strontium Eucommia ulmoides polysaccharides and in vitro evaluation of their osteoimmunomodulatory property.

The osteoimmune environment plays indispensable roles in bone regeneration because it determines subsequent osteogenesis and osseointegration. Eucommia ulmoides polysaccharide (EUP) was proved to be an effective biomaterial that has immunomodulatory effects for improving the biomechanical quality of bone. Strontium is a trace element that inhibits inflammation and promotes bone growth. To develop a novel EUP-based osteoimmunomodulatory biomaterial with potentially enhanced bone regeneration, we synthesized strontium Eucommia ulmoides polysaccharides (EUP-Sr) and evaluated its morphology, structure and thermal stability. The materials characterization results confirmed that strontium was successfully introduced into the EUP and formed a new complex with thermal-stable property. The cytocompatibility evaluation of different concentrations of EUP-Sr by CCK8 assay suggested that EUP-Sr is beneficial to the macrophages proliferation. We further evaluated the gene expressions of RAW 264.7 cells treated with EUP-Sr. It was found that EUP-Sr could suppress inflammatory factors and osteoclastogenesis, and enhance the expressions of osteogenic factors of RAW 264.7 cells. Therefore, EUP-Sr should be a promising bioactive compound with the capability to create a positive pro-regenerative environment for skeleton tissue engineering.

Synthesis of chondroitin sulfate magnesium for osteoarthritis treatment.

Magnesium chondroitin sulfate (MgCS) has been fabricated and characterized in this study. We investigated its morphology, composition as well as structure. The results verify that the sodium of sodium chondroitin sulfate (CS) is successfully replaced by magnesium and formed a polysaccharide-metal ion complex. To evaluate the clinical potential of MgCS, cell proliferation and apoptosis test were conducted. The results reveal that MgCS could effectively increase the proliferation and decrease the apoptosis of osteoarthritis (OA) chondrocytes. Moreover, real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to evaluate the gene expression level. RT-qPCR analysis suggests that MgCS could significantly increase the expression of COLII and decrease the expression of IL-1ß and iNOS in OA chondrocytes. Furthermore, significant upregulation of Bcl-2 mRNA expression and downregulation of the expression of apoptosis related gene p53 were observed. Thus, it is indicated that MgCS should have great potentials in OA treatment.

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.

Alginate/chondroitin sulfate based hybrid hydrogel with different molecular weight and its capacity to regulate chondrocytes activity.

Chondrocytes culture within three-dimensional (3D) hydrogels is an attractive strategy for expanding their potential in various biomedical applications. Molecular weight (MW) of the polymers used for preparing one-component hydrogels for 3D cell culture can affect the activity of chondrocytes. However, whether MW of double network hydrogels affects cell fate remains to be determined. Here, a ternary hydrogel was employed to encapsulate chondrocytes. By altering MW of alginate, the hybrid hydrogels with different mechanical properties were prepared. The effects of MW on the properties of hydrogels were evaluated in this work. Cell results revealed that chondrocytes encapsulated in low-MW hydrogels exhibited the best results on maintaining cell viability and inhibiting cell death. Additionally, RT-qPCR analysis suggested that the expression of COLII was increased while the expression of IL-1ß and iNOS was decreased in chondrocytes encapsulated in low-MW hydrogels. Hence, it is reasonable to be expected that the developed low-MW hydrogel should be a promising candidate for cartilage tissue engineering.