ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Lijie Mao,Long Bai,Xinqing Wang,Xiaolei Chen,Dong Zhang,Fangping Chen,Changsheng Liu
Bone regeneration is a well-orchestrated process involving electrical, biochemical, and mechanical multiple physiological cues. Electrical signals play a vital role in the process of bone repair. The endogenous potential will spontaneously form on defect sites, guide the cell behaviors, and mediate bone healing when the bone fracture occurs. However, the mechanism on how the surface charges of implant potentially guides osteogenesis and osteoimmunology has not been clearly revealed yet. In this study, piezoelectric BaTiO3/β-TCP (BTCP) ceramics are prepared by two-step sintering, and different surface charges are established by polarization. In addition, the cell osteogenesis and osteoimmunology of BMSCs and RAW264.7 on different surface charges were explored. The results showed that the piezoelectric constant d33 of BTCP was controllable by adjusting the sintering temperature and rate. The polarized BTCP with a negative surface charge (BTCP−) promoted protein adsorption and BMSC extracellular Ca2+ influx. The attachment, spreading, migration, and osteogenic differentiation of BMSCs were enhanced on BTCP–. Additionally, the polarized BTCP ceramics with a positive surface charge (BTCP+) significantly inhibited M1 polarization of macrophages, affecting the expression of the M1 marker in macrophages and changing secretion of proinflammatory cytokines. It in turn enhanced osteogenic differentiation of BMSCs, suggesting that positive surface charges could modulate the bone immunoregulatory properties and shift the immune microenvironment to one that favored osteogenesis. The result provides an alternative method of synergistically modulating cellular immunity and the osteogenesis function and enhancing the bone regeneration by fabricating piezoelectric biomaterials with electrical signals.
研究领域:
生物医学工程
·
组织工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Dong Yang,Chang Shu,Chengwei Xu,Xingjie Zan,Shaoyin Wei,Chenglong Wang,Lianxin Li
Osteomyelitis represents a significant health concern, characterized by a bacterial infection that can potentially present a considerable challenge to clinical treatment. Current treatment strategies, including prolonged antibiotic regimens and surgical debridement, often fail to adequately resolve infection or support bone regeneration, largely due to the pathogen-induced dysregulation of the bone microenvironment. This study reports a multifunctional capsule that achieves coordinated bacterial capture-killing and immunomodulatory within osseous tissue, effectively resolving the dual pathological challenges of persistent infection microenvironment and dysregulated bone regeneration inherent to osteomyelitis. The capsules, PC-O@TOB, are based on the Schiff base reaction of procyanidins (PC) with the amino of Lysine6-osteogenic growth peptide (K6-OGP) and tobramycin (TOB), which allows for efficient loading and controllable release of K6-OGP and TOB. In vitro and in vivo studies demonstrated that PC-O@TOB exhibits dual functionality: potent bactericidal activity through bacterial capture and localized antibiotic delivery, and microenvironmental remodeling via ROS scavenging and M2 macrophage polarization. This immunomodulatory effect synergizes with the capsule's osteogenic and angiogenic properties to accelerate bone repair. The strategy based on antibacterial and later bone microenvironment remodeling has opened up a new way for the treatment of osteomyelitis.
研究领域:
医学
·
生物材料学
·
感染与免疫
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Xu Wei,Chang Wan,Xu Peng,Yihao Luo,Mengyue Hu,Can Cheng,Shaoxiong Feng,Xixun Yu
Biomaterials with dual functions of osteoimmunomodulation and bone repair are very promising in the field of orthopedic materials. For this purpose, we prepared a copper-based carbon dots (CuCDs) and doped it into oxychondroitin sulfate / poly-acrylamide hydrogel (OPAM) to obtain a hybrid hydrogel (CuCDs/OPAM). We evaluated its osteoimmunomodulatory and bone repair properties in vitro and in vivo. The obtained CuCDs/OPAM exhibited good rBMSCs-cytocompatibility and anti-inflammatory properties in vitro. It also could effectively promote rBMSCs differentiation and the expression of osteogenic differentiation factor from rBMSCs under an inflammatory environment. Moreover, CuCDs/OPAM could induce macrophage phenotype switching (from M1-type macrophages to M2-type macrophages) in vivo which was beneficial to anti-inflammatory and present a good osteoimmunomodulation capability to induce a bone immune microenvironment to promote the differentiation of rBMSCs. In conclusion, CuCDs/OPAM hydrogel has dual functions of osteoimmunomodulatory and bone repair, and is a promising bone filling and repair material.
研究领域:
生物材料
·
骨科
·
组织工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Yaping Wang,Jingrong Wang,Rui Gao,Xiang Liu,Zujian Feng,Chuangnian Zhang,Pingsheng Huang,Anjie Dong,Deling Kong,Weiwei Wang
The reconstruction of large cranial bone defects by bioactive materials without exogenous cells or growth factors remains a substantial clinical challenge. Here, synthetic fibrous glycopeptide hydrogel (GR gel ) self-assembled by β-sheet RADA16-grafted glucomannan was designed to mimic the glycoprotein composition and the fibrillar architecture of natural extracellular matrix (ECM), which was non-covalently composited with 3D-printed polycaprolactone/nano hydroxyapatite (PCL/nHA) scaffold for cranial bone regeneration . The glycopeptide hydrogel significantly promoted the proliferation, osteogenic differentiation of bone mesenchymal stem cells (BMSCs), which was further augmented by GR gel -induced macrophage M2-phonotype polarization and the effective M2 macrophage-BMSC crosstalk . The repair of critical-size skull bone defect in rat indicated a superior efficacy of PCL/ [email protected] gel implant on bone regeneration and osseointegration , with an average bone area of 83.3% throughout the defect location at 12 weeks post treatment. Furthermore, the osteo-immunomodulatory GR gel induced a reparative microenvironment similar with that in normal cranium, as characterized by an increased percentage of anti-inflammatory M2 macrophages and osteoblasts, and high-level vascularization . Collectively, the composite scaffold developed here with macrophage polarization-mediated osteo-immunomodulation may represent a promising implant for expediting in situ bone regeneration by providing biochemical and osteoinductive cues at the injured tissue.
研究领域:
生物材料学
·
组织工程学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Wuyan Xu,Kun Liu,Jiaqing Chen,Junliang Liu,Siming Li,Hua Wang,Binghong Luo,Qingqi Meng
Bone regeneration is clinically challenging because vascularization, osteo-induction, and immune modulation are difficult to synchronize. Inspired by the native periosteum's bilayer architecture and multifunctional roles, we developed a wood-engineered Janus periosteum (EW-P-D@HACA-T) that integrates deferoxamine (DFO)-functionalized elastic wood (EW-P-D) with a bio-adhesive catechol-modified hyaluronic acid/tricalcium phosphate hydrogel (HACA-T). This construct mimics the anisotropic structure and compartmentalized functions of natural periosteum, providing dual support for angiogenesis and osteo-immunomodulation. EW-P-D maintains mechanical integrity and guides cell orientation, while sustained release activates the HIF-1α/VEGF pathway to enhance endothelial maturation and bone formation. Concurrently, the HACA-T composite hydrogel promotes osteogenic differentiation and polarizes macrophages toward an M2 phenotype, creating a pro-regenerative immune microenvironment. Furthermore, transcriptomic profiling revealed coordinated activation of p53, TGF-β, and ECM remodeling pathways, highlighting the scaffold's capacity to orchestrate tissue regeneration at the molecular level. In vivo evaluation using a rat skull defect model confirmed superior bone bridging, collagen deposition, neovascularization, and systemic biosafety. This study presents a structurally and functionally integrated wood-engineered periosteum substitute, demonstrating a paradigm shift toward engineered solutions that synchronize mechanical, angiogenic, and immunomodulatory cues for bone defect repair.
研究领域:
生物材料学
·
组织工程
·
免疫调控
·
骨科学
·
分子生物学
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Xuezhe Liu,Xingan Qiu,Pengren Peng,Qiqi Lv,Meijun Tan,Liangshuai Zhang,Qian Feng,Kaiyong Cai
Implants fail due to aseptic loosening remains a critical challenge in orthopedic surgery. This condition arises from poor early-stage osseointegration caused by the bioinert implant interface. Designing immune-active implant coating to timely create a regenerative osteoimmune microenvironment is a recent approach to promote new bone formation. Here, the transient hyperoxia-generating interface coupled with Mg 2+ delivery is developed for the titanium (Ti) to steer osseointegration. This design achieves strong adhesion (388.5 kPa) of the hydrogel coating, ensuring the interfacial stability. Under hypoxic conditions, the engineered interface mitigates cell death and promotes the shift from pro-inflammatory M1 to regenerative M2 macrophages. This immune transition enhances osteogenesis of mesenchymal stem cells (MSCs) and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro. Meanwhile, this modified surface demonstrates superior osseointegration results, with histological evidence showing earlier M2 macrophage existence and coordinated bone-vessel growth around the implants. By regulating natural bone healing phases—transient hyperbaric oxygen signaling synergies with Mg 2 ⁺ release for faster inflammation resolution—this platform creates a self-sustaining regenerative niche without exogenous biologics. The results provide a clinically viable strategy to improve implant integration by modulating the osteoimmune microenvironment.
研究领域:
生物材料学
·
免疫学
·
组织工程
·
骨科学
·
再生医学
·
纳米医学
·
转化医学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Xiaoyu Han,Jieliang Shen,Shuyu Chen,Zhengwei Cai,Ying Zhu,Weiwei Yi,Kai Li,Weiye Cai,Bailong Tao,Wenguo Cui,Dingqun Bai
Spatiotemporal Immune disorder is a key factor leading to the failure of bone tissue healing. It is of vital importance to accurately suppress excessive peak immune response within 24-48 h of the injury and so regulate the spatiotemporal osteoimmune disturbance of bones. In this study, Ultrasound Controlled “Explosive” (UCE) hydrogels were prepared from gelatin-hyaluronic acid methacrylate hydrogels loaded with resveratrol nanobubbles produced by double emulsification through a condensation reaction . Such materials innovatively enable ultrasound-controlled RES release for precise regulation of spatiotemporal osteoimmune disorders. Under an ultrasonic power level of 1.5 W/cm 2 , the rate of effectively released RES through the blast of UCE hydrogels reached 38.14 %. And compared with the control group, the in vivo inhibition of inflammation and osteogenesis effects of UCE hydrogels were more effective, respectively. As suggested by the results, the excessive local inflammatory response was inhibited by the release of resveratrol, the temporospatial disorder of bone immune was precisely regulated, and as a result, the process of bone repair was accelerated. Altogether, this study confirms that the newly created UCE Hydrogels effectively promote bone repair by intervening peak inflammation during the early phase of fracture healing .
研究领域:
生物材料
·
生物医学工程
·
组织工程
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Qing Wang,Ya Gao,Yanzheng Chen,Xuan Wang,Qingguo Pei,Taiyu Zhang,Changping Wang,Jinsong Pan
Bone implant-associated infections and inflammations, primarily caused by bacteria colonization, frequently result in unsuccessful procedures and pose significant health risks to patients. To mitigate these challenges, the development of engineered implants with spatiotemporal regulation capabilities, designed to inhibit bacterial survival and modulate immune responses in the early stage, while promoting bone defect healing in the late stage is proposed. The implants are functionalized with ε-poly-l-lysine-phenylboronic acid (PP) via dynamic boronic ester bonds, which facilitate its release through a reactive oxygen species (ROS) and pH-responsive strategy, thereby establishing an antibacterial microenvironment on and around the implants. Additionally, the dynamic metal coordination interaction facilitates the loading and sustained release of Sr 2+ under an acidic environment, providing immunomodulatory and osteogenic effects. The ROS/pH-responsive feature, coupled with the implant-bone tissue integration process, affords precise spatiotemporal regulation of the Ti-TA-Sr-PP implants. This strategy represents a promising approach for the preparation of advanced bone implants.
研究领域:
生物材料
·
组织工程
·
生物医学工程
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Advances
·
2022
·
IF 9.918
Yang Peng,Jie Yang,Wei Fu,Qiuying Gao,Shiyu Yao,Cheng Peng,Shuai Hou
The inflammation aroused by implants is the main cause of implant failure. Therefore, the design paradigm of implants has changed from “inertia” to “immunomodulatory”. Although multiple bioactive ions exert effects on osteogenesis, how magnesium ions (Mg 2+ ) manipulate immune response via inducing macrophage polarization and subsequently promote osteogenesis needs further investigation. In this study, phase-transited lysozyme (PTL) is deposited onto the surface of titanium (Ti) to construct a functional coating and magnesium chloride solution at 2.5 mM, 5 mM and 10 mM was utilized to produce PTL coatings with different concentrations of Mg 2+ (PTL-Mg2.5, PTL-Mg5 and PTL-Mg10). The characterization of the magnesium-doped PTL coatings (PTL-Mg) was tested by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and inductively coupled plasma atomic emission spectroscopy (ICP-AES). In addition, we utilized a co-culture system of macrophages and rat bone merrow mesenchymal stem cells (BMSCs) to investigate the osteoimmunomodulatory effects of PTL-Mg coatings. The results showed that compared with other groups, PTL-Mg5 group can create a favorable osteoimmune microenvironment by regulating macrophages polarization and release of inflammatory cytokines, then promote adhesion, proliferation and osteogenic differentiation of BMSCs. The in vivo results further verified the most excellent osteointegration ability of PTL-Mg5 in rat femur lateral condyle defects. This work indicates a promising way for design paradigm of implants with immunomodulatory properties by inducing PTL-Mg5 coating on Ti, providing a new strategy for implants surface modification.
研究领域:
生物材料
·
组织工程
·
免疫学
·
骨科
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 12
·期 1
·2201661
·
IF 11.092
Zonghan Xu,Liang Wu,Yu Tang,Kun Xi,Jincheng Tang,Yichang Xu,Jingzhi Xu,Jian Lu,Kaijin Guo,Yong Gu,Liang Chen
The bone immune microenvironment (BIM) regulates bone regeneration and affects the prognosis of fractures. However, there is currently no effective strategy that can precisely modulate macrophage polarization to improve BIM for bone regeneration. Herein, a hybridized biphasic bionic periosteum, inspired by the BIM and functional structure of the natural periosteum, is presented. The gel phase is composed of genipin-crosslinked carboxymethyl chitosan and collagen self-assembled hybrid hydrogels, which act as the “dam” to intercept IL-4 released during the initial burst from the bionic periosteum fiber phase, thus maintaining the moderate inflammatory response of M1 macrophages for mesenchymal stem cell recruitment and vascular sprouting at the acute fracture. With the degradation of the gel phase, released IL-4 cooperates with collagen to promote the polarization towards M2 macrophages, which reconfigure the local microenvironment by secreting PDGF-BB and BMP-2 to improve vascular maturation and osteogenesis twofold. In rat cranial defect models, the controlled regulation of the BIM is validated with the temporal transition of the inflammatory/anti-inflammatory process to achieve faster and better bone defect repair. This strategy provides a drug delivery system that constructs a coordinated BIM, so as to break through the predicament of the contradiction between immune response and bone tissue regeneration.
研究领域:
组织工程
·
再生医学
·
免疫学
·
生物医学工程
·
骨生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Min He,Qian Wang,Yunbo Feng,Xinghui Gao,Chao He,Jiangge Li,Weifeng Zhao,Weidong Tian,Changsheng Zhao
Implanted bone scaffolds or their biodegradation products may disturb the sequential functions of distinct macrophage phenotypes and cause improper timing of macrophage activation, resulting in delayed or dysfunctional bone regeneration. Although spatiotemporal manipulation of the immune response has been recognized as a promising strategy to address this issue, developing satisfactory drug delivery systems with the function of proper timing control on the macrophage phenotype transformation from pro-inflammatory M1 to anti-inflammatory M2 phenotype still remains a challenge. Here, we propose an amphiphilic nanomedicine with dual anti-inflammatory functions and inflammation-responsive drug release properties to spatiotemporally manage the osteoimmunomodulation of the bone scaffold. The nanomedicine enables the modified scaffold to manipulate the immune response in a staged manner, not only avoiding the overinhibition of M1 macrophages in the initial phase but also facilitating its polarization to M2 phenotype, as well as exhibiting full-course inhibition on later biodegradation-induced inflammation. The described immunomodulatory manner attempts to conform to the principle of osteoimmunomodulation, consequently resulting in better in vivo osteogenesis compared with traditional drug delivery systems. We anticipate that this strategy might aid the development of advanced immunomodulatory bone biomaterials.
研究领域:
生物材料科学
·
免疫学
·
组织工程
·
药剂学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Junyao Cheng,Hufei Wang,Ming Li,Jianpeng Gao,Xiao Liu,Chuyue Zhang,Pengfei Chi,Bo Li,Yuan Xve,Daoyang Fan,Zheng Wang,Jianheng Liu,Xing Wang,Licheng Zhang
The development of bone adhesives capable of restoring natural bone structure and function represents a pioneering advancement in surgical technology, offering significant potential to improve the treatment outcomes of comminuted fractures. However, the development of a clinically demand-driven adhesive, ensuring both reliable adhesion and osteogenic activity, poses a significant challenge. Herein, a structurally and functionally dual-biomimetic bone adhesive is developed through the design of an organic–inorganic network-enhanced hydrogel, which integrates caffeic acid-grafted collagen (CAC), aminated laponite (ALAP), and N-hydroxysuccinimide ester-terminated polyethylene glycol (tetra-PEG-SC). Benefiting from nanosheet-induced strengthening, the mechanically reinforced adhesive can maintain integrity under extreme compression (98%) and tensile (600%) deformations, facilitating anatomical repositioning of rabbit radius and porcine femur fractures. Of greater importance, the adhesive accelerated fracture healing, potentially via ROS scavenging and immunomodulation, as evidenced by reduced oxidative stress and M2 macrophage polarization in vitro. Assessed through an innovative rabbit radius comminuted fracture model, the injectable bone adhesive demonstrates rapid and flexible adhesion of bone fragments in a blood-rich environment, as observed over the 2 fold improvement in biomechanical and radiological performance compared with commercially available cyanoacrylate adhesives. This intricately designed bone adhesive holds promise as a novel solution for addressing complex fracture cases in surgical treatment.
研究领域:
生物医学工程
·
生物材料
·
组织工程
·
骨科手术
·
免疫调节
·
纳米技术
✓ 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）