Journal of Orthopaedic Translation
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2025
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IF 7.8
Jiaxin Zhang,Haotian Bai,He Liu,Xiaonan Wang,Mingwei Xu,Guokun Zhang,Zexin Di,Xin Zhao,Jincheng Wang,Luquan Ren
Rationale Imbalances in the osteogenic–osteoclastic microenvironment hinder effective osseointegration between the prosthesis and host bone, which is a key factor contributing to the high incidence of prosthesis loosening and periprosthetic fractures in osteoporosis patients. Developing an implant interface that can reverse the dysregulated osteogenic microenvironment is an effective strategy to address this challenge. Methods A novel bioinspired interface with a spatial gradient structure was engineered by 3D-printed porous titanium alloy implants and hollow mesoporous silica nanoparticles coating. Apart from the bioinspired bone microstructure, the amine-functionalized nanocoating of the bioactive interface could also load and temporally sustain the zoledronic acid (ZOL) release. A series of in vitro experiments were carried out to characterize the bioactive interface and to clarify the regulation of osteogenic–osteoclastic balance by ZOL temporal release from the nanocoatings. Afterward, an osteoporotic model was utilized to validate the in vivo bioactive interface osseointegration effect. Results Based on the structural features and chemical properties of the bioactive interface, efficient ZOL loading was achieved. Additionally, the temporal release mechanism of ZOL through free diffusion and ionic bond ionization enabled long-term sustained release. Meanwhile, the early high-concentration local release of ZOL effectively inhibited osteoclast formation and activation in the microenvironment. As the ZOL release decreased over time, the focus shifted to promoting the process of bone formation, thereby reversing the dysregulated osteogenic microenvironment. According to this, we identified the optimal gradient concentration (10 -5 M) of the ZOL temporal release system that efficiently exerts bidirectional regulatory effects. Most notably, the spatial gradient structured interface loaded with this optimal concentration of ZOL (10 -5 M) significantly augmented osseointegration under in vivo osteoporotic conditions. Conclusion Overall, our study provides a novel nanocoating capable of temporally releasing ZOL to reverse the dysregulated osteogenic microenvironment, aiming to maintain the long-term stability of artificial prostheses for osteoporosis patients. The translational potential of this article This study validates the structure–performance-effect relationship of ZOL-releasing nanocoatings with a temporal release mechanism, providing a novel approach to addressing the high incidence of postoperative complications in osteoporotic patients undergoing prosthetic replacement.
研究领域:
生物医学工程
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骨科
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材料科学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2021
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IF 8.947
Yiting Zhao,Yixian Zhou,Dan Yang,Xinyi Gao,Ting Wen,Jintao Fu,Xinguo Wen,Guilan Quan,Xin Pan,Chuanbin Wu
Cutaneous melanoma is one of the most common malignant skin cancer with high lethality. Chemotherapy and photothermal therapy are important and extensively studied treatment modalities for melanoma. However, these therapies still face some challenges, which severely restrict their further applications, such as unsatisfactory efficacy of monotherapy, nonspecific uptake and release during drug delivery, and unexpected adverse effects from system administration. Recently, the strategies of collaboration, functional modification, stimuli-responsive design, and topical administration all show great prospect for solving above problems. In this research, a multifunctional nanoparticle-integrated dissolving microneedle drug delivery system was constructed, in which the nanoparticles were prepared based on the framework with the incorporation of photothermal agent (CuS) into Zeolitic imidazolate framework-8 and functionalized by hyaluronic acid . This system can co-load multi-modal drugs, improve specific uptake and distribution of targeted tumor, deliver drug locally, and release drug intelligently and spatiotemporally, thereby promising a low-dose administration with high efficiency. The high inhibiting tumor performance and excellent systematic safety were verified both in vitro and in vivo . Together, this smart design overcame the drawbacks of monotherapy and conventional system administration. We believe the nanoparticle-integrated dissolving microneedles will be in prospect of clinical application for more superficial tumors with further delicate optimization. Statement of significance Melanoma is one of the most common skin cancers with high lethality. Extensively studied chemotherapy and photothermal therapy still face some challenges, such as the limited therapeutic efficacy and the severe system adverse effects. In order to overcome these drawbacks, the multifunctional nanoparticle-integrated dissolving microneedles (DMNs) were designed. Especially, the nanoparticles could co-load multi-modal drugs, improve specific uptake, and release drug intelligently and spatiotemporally. The microneedles could increase the drug accumulation in tumor, thus achieving excellent therapeutic efficacy and reducing side effects. This system paved the way to a less invasive, more focused and efficient therapeutic strategy for melanoma therapy.
研究领域:
肿瘤学
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药学
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纳米技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
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IF 13
Junwu Wang,Yilong Huang,Tian Luan,Pengzhi Shi,Lanhong Guo,Qi Zhang,Guang Shi,Zhuowen Hao,Tianhong Chen,Liang Zhang,Jingfeng Li
Depletion of nucleus pulposus-derived stem cells (NPSCs) is a major contributing factor to the attenuation of endogenous regenerative capacity in intervertebral disc degeneration (IVDD). Introducing a hydrogel drug delivery system is a potential strategy for counteracting endogenous cell depletion. The present study proposes a delivery platform for the spatiotemporal release of multiple drugs by combining sodium alginate hydrogels with gelatin microgels (SCGP hydrogels). The SCGP hydrogels facilitated the initial release of chondroitin sulfate (ChS) and the gradual release of an independently developed parathyroid hormone-related peptide (P2). The combined action of these two small molecule drugs “awakened” the reserve NPSCs, mitigated cell damage induced by H 2 O 2 , significantly enhanced their biological activity, and promoted their differentiation toward nucleus pulposus cells. The mechanical and viscoelastic properties of the hydrogel are enhanced by physical and chemical dual cross-linking to adapt to the loading environment of the degenerated disc. A rat IVDD model is used to validate that the SCGP hydrogel can significantly inhibit the progression of IVDD and stimulate the endogenous repair of IVDD. Therefore, the spatiotemporal differential drug delivery system of the SCGP hydrogel holds promise as a convenient and efficacious therapeutic strategy for minimally invasive IVDD treatment.
研究领域:
生物医学工程
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组织工程
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干细胞生物学
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药物递送系统
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULES
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2021
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IF 5.985
Yaxin Qiu,Dheeman-Roy Munna,Fang Wang,Juqun Xi,Zhifeng Wang,Defeng Wu
For shape-memory polymers (SMPs), introducing material heterogeneity is vital to tailor shape-shifting pathways. However, it is hard to reprogram the heterogeneity for both covalent networks and dynamic covalent networks after these networks are encoded. Here, photoactive coumarin derivative end-capped dangling chains were used to participate in building photoreversible polycaprolactone/poly(malic acid) networks, endowing the networks with reprogrammable heterogeneity and a capability of room-temperature storage of entropic energy. The alternations of network topology with 365/254 nm UV irradiation and strain-induced crystallization behavior of as-prepared bio-based elastomers were studied, aiming at quantitatively guiding the spatiotemporal release of entropic energy to regulate asynchronous deformations. This work provides applicable methods for simplifying shaping manipulation or for diversifying shape-shifting pathways of SMPs.
研究领域:
材料科学
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高分子化学
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2023
·Vol. 21
·期 1
·1-20
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IF 10.2
Dong Lanlan,Huang Can,Zhao Baohua,Hu Guangyun,Huang Yong,Zhang Xiaorong,Hu Xiaohong,Wang Ying,XiaoyanSun,Qian Wei,Luo Gaoxing
Suppressing persistent multidrug-resistant (MDR) bacterial infections and excessive inflammation is the key for treating chronic wounds. Therefore, developing a microenvironment-responsive material with good biodegradability, drug-loading, anti-infection, and anti-inflammatory properties is desired to boost the chronic wounds healing process; however, using ordinary assembly remains a defect. Herein, we propose a pH/enzyme dual-responsive polymyxin B (PMB) spatiotemporal-release hydrogel (GelMA/OSSA/PMB), namely, the amount of OSSA and PMB released from GelMA/OSSA/PMB was closely related the wound pH and the enzyme concentration changing. The GelMA/OSSA/PMB showed better biosafety than equivalent free PMB, owing to the controlled release of PMB, which helped kill planktonic bacteria and inhibit biofilm activity in vitro. In addition, the GelMA/OSSA/PMB exhibited excellent antibacterial and anti-inflammatory properties. A MDR Pseudomonas aeruginosa caused infection was effectively resolved by the GelMA/OSSA/PMB hydrogel in vivo, thereby significantly boosting wound closure during the inflammatory phase. Furthermore, GelMA/OSSA/PMB accelerated the sequential phases of wound repair.
研究领域:
生物医学工程
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材料科学
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药物学
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伤口愈合
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传染病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）