NATURE MATERIALS
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2025
·
IF 38.5
Han Jinpeng,Wu Zhaoyuan,Zhan Shumin,Sheng Tao,You Jiahuan,Yu Jicheng,Fu Junfen,Zhang Yuqi,Gu Zhen
Timing dosing throughout the day impacts the therapeutic efficacy and side effects of medications. Thus, optimizing release profiles to synchronize drug concentrations with natural rhythms is critical for optimal therapeutic benefits. However, existing delivery systems are still inefficient in delivering drugs in a biorhythm-mimicking fashion. Here we describe a biorhythm-inspired growth hormone transdermal microneedle patch with multistage drug release that mimics the natural rhythm of human growth hormone secretion at night. Programmed drug release is achieved by combining a ‘burst-release’ module with several ‘delayed-release’ modules. Compared with the subcutaneous daily injections currently used in clinics, the patch exhibits enhanced efficacy in terms of longitudinal bone growth and bone quality, leading to bone length increases of ~10 mm and ~5 mm in healthy rats and growth hormone gene knockout mice, respectively. Our findings reveal that the biorhythm-mimicking release pattern significantly enhances growth hormone bioavailability and effectively regulates the growth-related biological process, thus boosting the secretion of insulin-like growth factor-1 and ultimately promoting bone growth.
研究领域:
药理学
·
生物医学工程
·
内分泌学
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2025
·
IF 7.9
Wenjie Wang,Lingling Zheng,Wei Liu,Chunjuan Wang,Dan Chen,Liya Ai,Antonio Apicella,Chao Wang,Yubo Fan
To address the challenge of vertical bone augmentation in orofacial surgery and implant dentistry, this study focused on additively manufactured 3D architectural glass–ceramic scaffolds (3DP). The 3DP, which mimics the Haversian canal and trabecular porous structure, was innovatively designed and fabricated using Digital Laser Processing (DLP) additive manufacturing. The morphology, microstructure, elemental composition and mechanical characteristics of 3DP were compared with those of bovine Xenogeneic Bone Block (XBB), human Allogeneic Bone Block (ABH), and rabbit Autogenous Bone Block (ABR). Furthermore, the vertical osteogenic capacity using a rabbit calvarium model were compared among them. Micro-CT and histology analyses revealed that the osteogenic height, volume, and area of 3DP and XBB were superior to those of ABH and ABR, and 3DP demonstrated a more rapid vertical osteogenesis compared to XBB. The excellent vertical osteogenic performance of 3DP should be attributed to the ideal pore size of its microporous structure, the spatial maintaining force of its overall architecture, and its microcrystalline chemical composition after sintering. Moreover, the vertical channels in the porous network seemed to promote the rapid vertical growth of bone tissue at the early stage.
研究领域:
口腔医学
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组织工程学
·
材料科学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Yuqing Deng,Fenbo Ma,L.I. Ruiz-Ortega,Ying Peng,Ye Tian,Wenqi He,Bin Tang
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.
研究领域:
生物材料
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组织工程
·
免疫学
·
骨再生
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2025
·
IF 5.5
Yupu Yang,Yu Liu,Shengmiao Wang,Xinyu Feng,Jing Lan,Zheqin Dong
Tooth extraction often leads to significant alveolar bone resorption, posing a major clinical challenge that compromises subsequent prosthodontic rehabilitation. This impaired bone regenerative capacity is primarily attributed to excessive reactive oxygen species (ROS), insufficient angiogenesis, and inadequate osteoinductive stimulation within the socket, collectively delaying the healing process. To address this, we developed an injectable dual-network hydrogel system loaded with metal–organic framework (MOF) and osteogenic growth peptide (OGP) to promote the tooth extraction socket healing. The double-network hydrogel, composed of gelatin methacryloyl (GelMA) and oxidized dextran (ODex), forms a dynamic network through the Schiff base reaction between the amino groups of GelMA and the aldehyde groups of ODex, enabling injectability and adaptation to the irregular shape of the socket, while the second covalent network, formed by photo-cross-linking, enhances its mechanical properties. Besides, MOF decomposes to release magnesium ion (Mg2+) and gallic acid (GA) to eliminate excess ROS and promote endothelial cell differentiation, facilitating angiogenesis, while OGP is an efficient osteoinductive agent. In vitro studies demonstrate that the composite hydrogel system efficiently exerts antioxidant properties to eliminate ROS, promotes angiogenesis, and enhances osteogenesis. Moreover, in vivo trials show that the composite hydrogel facilitates angiogenesis and bone formation in the tooth extraction socket, ultimately promoting the bone repair process.
研究领域:
生物材料
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组织工程
·
牙科医学
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再生医学
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纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BONE AND MINERAL RESEARCH
·
2023
·Vol. 38
·期 4
·556-567
·
IF 6.2
Ruiye Bi,Xueting Luo,Qianli Li,Peiran Li,Haohan Li,Yi Fan,Binbin Ying,Songsong Zhu
Temporomandibular joint (TMJ) growth requires orchestrated interactions between various cell types. Recent studies revealed that fibrocartilage stem cells (FCSCs) in the TMJ cartilage play critical roles as cell resources for joint development and repair. However, the detailed molecular network that influences FCSC fate during TMJ cartilage development remains to be elucidated. Here, we investigate the functional role of Igf1 in FCSCs for TMJ cartilage growth and homeostasis by lineage tracing using Gli1-CreER + ; Tm flfl mice and conditional Igf1 deletion using Gli1-/Col2-CreER + ; Igf1 fl/fl mice. In Gli1-CreER + ; Tm flfl mice, red fluorescence + (RFP + ) FCSCs show a favorable proliferative capacity. Igf1 deletion in Gli1 + / Col2 + cell lineages leads to distinct pathological changes in TMJ cartilage. More serious cartilage thickness and cell density reductions are found in the superficial layers in Gli1-CreER + ; Igf1 fl/fl mice. After long-term Igf1 deletion, a severe disordered cell arrangement is found in both groups. When Igf1 is conditionally deleted in vivo, the red fluorescent protein-labeled Gli1 + FCSC shows a significant disruption of chondrogenic differentiation, cell proliferation, and apoptosis leading to TMJ cartilage disarrangement and subchondral bone loss. Immunostaining shows that pAkt signaling is blocked in all cartilage layers after the Gli1 + -specific deletion of Igf1 . In vitro, Igf1 deletion disrupts FCSC capacities, including proliferation and chondrogenesis. Moreover, the deletion of Igf1 in FCSCs significantly aggravates the joint osteoarthritis phenotype in the unilateral anterior crossbite mouse model, characterized by decreased cartilage thickness and cell numbers as well as a loss of extracellular matrix secretions. These findings uncover Igf1 as a regulator of TMJ cartilage growth and repair. The deletion of Igf1 disrupts the progenitor capacity of FCSCs, leading to a disordered cell distribution and exaggerating TMJ cartilage dysfunction. © 2023 American Society for Bone and Mineral Research (ASBMR).
研究领域:
发育生物学
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干细胞生物学
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骨科
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分子生物学
·
病理学
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DOI
PubMed
高影响因子
Military Medical Research
·
2023
·Vol. 10
·期 1
·1-23
·
IF 21.1
Yu Yong-Lin,Wu Jun-Jie,Lin Chuan-Chuan,Qin Xian,Tay Franklin R.,Miao Li,Tao Bai-Long,Jiao Yang
Background Treatment of methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium (Ti) implants. There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods Herein, an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles (PDA), nitric oxide (NO) release donor sodium nitroprusside (SNP) and osteogenic growth peptide (OGP) onto Ti implants, denoted as Ti-PDA@SNP-OGP. The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy, X-ray photoelectron spectroscope, water contact angle, photothermal property and NO release behavior. The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe, 1-N-phenylnaphthylamine assay, adenosine triphosphate intensity, o-nitrophenyl-β-d-galactopyranoside hydrolysis activity, bicinchoninic acid leakage. Fluorescence staining, assays for alkaline phosphatase activity, collagen secretion and extracellular matrix mineralization, quantitative real‑time reverse transcription‑polymerase chain reaction, and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells (MSCs), RAW264.7 cells and their co-culture system. Giemsa staining, ELISA, micro-CT, hematoxylin and eosin, Masson’s trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms, inhibition of inflammatory response, and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light irradiation, and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species (ROS)-mediated oxidative stress, destroying bacterial membrane integrity and causing leakage of intracellular components (P < 0.01). In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs, but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype (P < 0.05 or P < 0.01). The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways (P < 0.01). In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model (P < 0.01).Conclusion sThese findings suggest that Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.
研究领域:
生物材料
·
生物医学工程
·
微生物学
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免疫学
·
骨科
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Ce Zhu,Miaomiao He,Dan Sun,Yong Huang,Leizhen Huang,Meixuan Du,Jingcheng Wang,Juehan Wang,Zhongyang Li,Bowen Hu,Yueming Song,Yubao Li,Ganjun Feng,Limin Liu,Li Zhang
In this work, we developed the first 3D-printed polyetheretherketone (PEEK)-based bone scaffold with multi-functions targeting challenging bone diseases such as osteosarcoma and osteomyelitis. A 3D-printed PEEK/graphene nanocomposite scaffold was deposited with a drug-laden (antibiotics and/or anti-cancer drugs) hydroxyapatite coating. The graphene nanosheets within the scaffold served as effective photothermal agents that endowed the scaffold with on-demand photothermal conversion function under near-infrared laser irradiation. The bioactive hydroxyapatite coating significantly boosted the stem cell proliferation in vitro and promoted new bone growth in vivo. The presence of antibiotics and anti-cancer drugs enabled eradication of drug-resistant bacteria and ablation of osteosarcoma cancer cells, the treatment efficacy of which can be further enhanced by on-demand laser-induced heating. The promising results demonstrate the strong potential of our multi-functional scaffold in applications such as bone defect repair and multimodal treatment of osteosarcoma and osteomyelitis.
研究领域:
生物医学工程
·
材料科学
·
骨科
·
癌症研究
·
感染性疾病
✓ 已验证
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2021
·
IF 7.991
Chengzhe Gao,Zongliang Wang,Zixue Jiao,Zhenxu Wu,Min Guo,Yu Wang,Jianguo Liu,Peibiao Zhang
The overall aim of the current study is to develop a dual-functional PEEK implant to simultaneously fight off bacterial contamination and promote osseointegration by sustained release of moxifloxacin hydrochloride (MOX) and osteogenic growth peptide (OGP) from mussel-inspired polydopamine (PDA)-coated porous sulfonated PEEK (SPK) surface. Our study revealed that the MOX/OGP PDA-modified SPK (SPD-MOX/OGP) surface exhibited a durable and excellent antibacterial effect against planktonic/adherent Staphylococcus aureus and Escherichia coli in vitro . A remarkable enhancement in specific cell adhesion, proliferation and osteogenicity were observed on the SPD-MOX/OGP substrate due to the presence of OGP and PDA molecules compared to all other groups. More significantly, using the infected and non-infected rat tibia models confirmed the in vivo antimicrobial and osteogenesis abilities of SPD-MOX/OGP. Therefore, we are confident that such dual-functional PEEK surface with both antibacterial and osseointegrative capacities in this study would give a positive answer to periprosthetic joint infection-related issues.
研究领域:
生物材料
·
生物医学工程
·
骨科
·
传染病
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Bailong Tao,Chuanchuan Lin,Ye He,Zhang Yuan,Maowen Chen,Kun Xu,Kai Li,Ai Guo,Kaiyong Cai,Lixue Chen
Bacterial infection and the resulting inflammation response not only affect the functions of osteogenic-relative cells but also lead to the failure of titanium (Ti)-based implantation. It is urgent to develop multifunctional (antimicrobial, anti-inflammation, and pre-osteogenesis) titanium implants to address this tissue. Herein, an osteogenic growth peptide (OGP) loaded zeolitic imidazolate frameworks-67 (ZIF-67) coating was fabricated on titanium dioxide nanotubes (TNTs) to prepare a [email protected] surface. The [email protected] coating was rapidly dissolved under an acidic environment with pH-sensitive property. Moreover, the [email protected] displayed a strong antibacterial activity against Escherichia coli ( E. coli ), Staphylococcus aureus ( S. aureus ), Streptococcus mutans ( S. mutans ), and methicillin-resistant Staphylococcus aureus ( MRSA ) owing to the hydrolysis of ZIF-67 nanoparticles and the formation of an alkaline microenvironment. The implants had good biocompatibility toward mesenchymal stromal cells (MSCs) and macrophages. Notably, the [email protected] could suppress the inflammatory response and simultaneously improve the cellular differentiation of MSCs under an inflammatory environment. In vivo study further revealed that [email protected] implants presented strong antimicrobial and anti-inflammatory properties at the early stage of implantation, thereby enhancing the osteointegration of bone-implant at the late stage. Thus, this multifunctional Ti implant combining osteoimmunomodulatory and antibacterial effects is a promising candidate for implant-associated infectious bone regeneration.
研究领域:
材料科学
·
生物医学工程
·
生物材料
·
骨科
·
免疫学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）