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Bioactive Materials · 2022 · IF 16.874

Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects

Shuaijie Li,Liyan Zhang,Chunyu Liu,Jua Kim,Kun Su,Tingli Chen,Limin Zhao,Xiaomei Lu,Hao Zhang,Yinglin Cui,Xu Cui,Feng Yuan,Haobo Pan

Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria, which include: 1) recruitment and polarization of the macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype, 2) enhance vascularization, and 3) activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing. So far, no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation, angiogenesis, and osteogenesis. Therefore, in this study, we designed bone cement comprised of strontium and copper-incorporated borosilicate glass (Sr/Cu-BSG) in the liquid phase of chitosan to modulate bone healing. In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1) while down-regulating pro-inflammatory genes(IL-1β and IL-6) in macrophages at 3 days. Sr and Cu ions also increased the expressions of angiogenic genes (VEGF and bFGF) in HUVECs at 5 days and osteogenic genes (Runx-2, OCN, and OPN) in hBMSCs at 7, 14, and 21 days. 5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory, angiogenic, and osteogenic properties among the bone cement groups with different Sr and Cu ratios. Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results, where the degradation rate of Sr/Cu-BSG matched the bone healing rate. Similar to in vitro , the 5Sr3Cu-BSG group also showed the highest bone formation in vivo. Excellent physical and chemical properties, along with its bone repairing ability, make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects.

研究领域: 生物材料 · 组织工程 · 骨科 · 生物医学工程 · 材料科学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Increased physiological osteochondral repair via space-specific sequestrating endogenous BMP-2 founctional hydrogel

Yuping Wang,Yiting Lei,Nan Wang,Jun Zhang,Wenguo Cui,Xiaoji Luo

The challenge of achieving graded regeneration of adjacent tissues remains significant in tissue repair and regeneration. For instance, the disruption of the microenvironment caused by “osteogenesis mobilization” often results in fibrosis of the regenerated cartilage, ultimately leading to osteoarthritis. Inspired by the utilization of activated carbon for adsorbing and filtering small particles in air purification and water treatment, we have designed an integrated hydrogel scaffold capable of absorbing the endogenous BMP-2 produced by “osteogenesis mobilization”, confining it to the bone defect area, and preventing its diffusion into the cartilage region, thereby facilitating physiological osteochondral gradient regeneration. The osteogenic layer of this integrated scaffold is NHAP-AHAMA-B2A, which captures the BMP-2 produced by “osteogenesis mobilization” and amplifies its osteogenic effect through the grafted peptide B2A. This upregulation enhances the expression of ALP, OCN, and OPN in MSCs within the osteogenic layer, promoting osteogenic differentiation. The chondrogenic layer, HAMA-B2A, utilizes the peptide B2A to upregulate the expression of COL II and ACAN in MSCs, fostering chondrogenic differentiation. This integrated HAMA-B2A/NHAP-AHAMA-B2A hydrogel scaffold confines the BMP-2 produced by “osteogenesis mobilization” to the bone defect area, prevents its diffusion into the cartilage defect area, and effectively utilizes it to induce stem cell osteogenic differentiation. Simultaneously, it induces stem cell chondrogenic differentiation in the cartilage defect area, achieving transparent cartilage regeneration. In summary, the osteogenic and chondrogenic layers of this integrated scaffold collaborate to achieve a physicochemical gradient regeneration of bone-cartilage.

CAS / MDL: 106797-53-9 760-93-0
研究领域: 组织工程 · 再生医学 · 生物材料科学 · 骨科
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Biomaterials Advances · 2024 · IF 5.5

Carboxymethyl chitosan/alendronate sodium/Sr2+ modified TiO2 nanotube arrays enhancing osteogenic activity and antibacterial property

Kunpeng Jia,Changpeng Zuo,Yan Xu,Wenfu Ma,Lingtao Wang,Yan Ji,Jie Chen,Qiuyang Zhang,Changjiang Pan,Tingting Liu

Titanium and its alloys are widely used as orthopedic implants owing to their good mechanical properties and excellent corrosion resistance. However, the insufficient osteogenic activity and antibacterial properties hinder their clinical applications. To address these issues, TiO 2 nanotube arrays (TNT) were first fabricated on the TA2 alloy surface via an anodizing technique, and strontium ions (Sr 2+ ) were then loaded by hydrothermal reaction (TNT + Sr) and annealing treatment (TNT + A). Subsequently, the polydopamine layer (TNT + PDA) was constructed to immobilize the carboxymethyl chitosan and alendronate sodium (TNT + CA) mixture. The prepared coatings were thoroughly characterized by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), X-ray photoelectron spectrometer (XPS), attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffractometer (XRD), and water contact angle measurement. The results confirmed that Sr 2+ ions, polydopamine, and carboxymethyl chitosan/alendronate sodium were successfully immobilized on the nanotubes. The coating of TNT + CA significantly enhanced the hydrophilicity, and effectively delayed the release of Sr 2+ and alendronate. The TNT + CA coating significantly promoted osteoblast adhesion and proliferation, and up-regulated the expressions of alkaline phosphatase (ALP), osteocalcin (OCN), and osteoblast-specific transcription factor (RUNX2). TNT + CA was able to rapidly induce in situ hydroxyapatite deposition from the simulated body fluid (SBF). Moreover, TNT + CA coating showed inhibition against Escherichia coli and Staphylococcus aureus (especially against Escherichia coli ). The prepared TNT + CA coating provides a novel strategy for enhancing bone affinity, improving osteoblast behaviors, and antibacterial properties of titanium-based biomaterials.

研究领域: 生物材料 · 骨科 · 表面工程 · 纳米技术 · 生物医学工程
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Dynamic Cross-Linking, Self-Healing, Antibacterial Hydrogel for Regenerating Irregular Cranial Bone Defects

Zuoxiang Dong,Jian Xu,Peng Lun,Zeyu Wu,Wenshuai Deng,Peng Sun

Given the widespread clinical demand, addressing irregular cranial bone defects poses a significant challenge following surgical procedures and traumatic events. In situ-formed injectable hydrogels are attractive for irregular bone defects due to their ease of administration and the ability to incorporate ceramics, ions, and proteins into the hydrogel. In this study, a multifunctional hydrogel composed of oxidized sodium alginate (OSA)-grafted dopamine (DO), carboxymethyl chitosan (CMCS), calcium ions (Ca2+), nanohydroxyapatite (nHA), and magnesium oxide (MgO) (DOCMCHM) was prepared to address irregular cranial bone defects via dynamic Schiff base and chelation reactions. DOCMCHM hydrogel exhibits strong adhesion to wet tissues, self-healing properties, and antibacterial characteristics. Biological evaluations indicate that DOCMCHM hydrogel has good biocompatibility, in vivo degradability, and the ability to promote cell proliferation. Importantly, DOCMCHM hydrogel, containing MgO, promotes the expression of osteogenic protein markers COL-1, OCN, and RUNX2, and stimulates the formation of new blood vessels by upregulating CD31. This study could provide meaningful insights into ion therapy for the repair of cranial bone defects.

研究领域: 材料科学 · 生物材料 · 组织工程 · 生物医学工程 · 骨科 · 再生医学
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EXPERIMENTAL CELL RESEARCH · 2023 · IF 3.7

Punicalagin attenuates TNF-α-induced oxidative damage and promotes osteogenic differentiation of bone mesenchymal stem cells by activating the Nrf2/HO-1 pathway

Lei Huang,Shunyi Lu,Mengxuan Bian,Jiayi Wang,Jieqin Yu,Jun Ge,Jian Zhang,Qintong Xu

Oxidative stress is one of the most important factors in changing bone homeostasis. Redox homeostasis plays a key role in the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) and the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) for bone regeneration. Currently, this study assessed the effects of punicalagin (PUN) on BMSCs and HUVECs. Cell viability was determined by CCK-8 assay. A flow cytometry analysis was adopted to detect macrophage polarization. The production of reactive oxygen stress (ROS), glutathione (GSH), malonaldehyde (MDA) and superoxide dismutase (SOD) activities were evaluated by using commercially-available kits. Osteogenic capacity of BMSCs was evaluated by ALP activity, ALP staining and ARS staining. The expression of osteogenic-related proteins (OCN, Runx-2, OPN) and Nrf/HO-1 levles were evaluated by Western blotting. Osteogenic-related genes (Osterix, COL-1, BMP-4, ALP) were evaluated by RT-PCR. Migration ability and invasion ability of HUVECs were evaluated by wound healing assay and Transwell assay. Angiogenic ability was detected by tube formation assay and the expression of angiogenic-related genes (VEGF, vWF, CD31) were evaluated by RT-PCR. Results showed that PUN alleviated oxidative stress by TNF-α, enhanced osteogenic differentiation in BMSCs and angiogenesis in HUVECs. Moreover, PUN regulate immune microenvironment by promoting the polarization of M2 macrophages and reduce the oxidative stress related products by activating Nrf2/HO-1 pathway. Altogether, these results suggested that PUN can promote osteogenic capacity of BMSCs, angiogenesis of HUVECs, alleviate oxidative stress via Nrf2/HO-1 pathway, offering PUN as a novel antioxidant agent for treating bone loss diseases.

CAS / MDL: 30525-89-4
研究领域: 药理学 · 细胞生物学 · 分子生物学 · 干细胞研究 · 骨再生
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