Frontiers in Bioengineering and Biotechnology
·
2025
·
IF 4.8
Yicai Luo,Ziwei Wu,Yingjuan Zhang,Yang Qiao,Yinge Wei,Xuan Yan,Xiangyu Ma,Xianxian Huang,Xiaoxia Zhong,Zhimao Ye,Xinping Lu,Hongbing Liao*
Introduction: Diabetes mellitus often leads to bone metabolism disorders, hindering bone regeneration and delaying the healing of bone defects. β-Ecdysone, a plant-derived hormone known for its wide range of physiological activities, possesses hypoglycemic effects and promotes osteogenic differentiation. This study developed a composite PLGA slow-release scaffold loaded with β-ecdysone to enhance its bioavailability through topical administration and to investigate its potential to heal diabetic bone defects.Methods: The composite scaffolds were fabricated using solution casting/particle leaching and freeze-drying techniques. Then a series of characterizations were subjected to test the performance of composite scaffolds, and in vitro safety of the composite scaffolds was tested by CCK8 assay and live/dead cell staining. Further, micro-CT and histology to evaluate the effect of β-E/PLGA composite scaffolds on healing of skull defects in diabetic rats at 4 and 8 weeks after implantation. Simultaneously, the safety of the scaffolds in vivo was also evaluated.Results: The material characterization results indicated that, in comparison to the single-pore size scaffold, the composite scaffold exhibited superior porosity, swelling ratio, drug loading capacity, and mechanical properties. Additionally, the composite scaffolds showed appropriate degradation performance and sustained drug release profiles. The CCK8 cytotoxicity assay and live/dead cell staining demonstrated that BMSCs survived and proliferated on the composite scaffold under both low-glucose and high-glucose conditions. Micro-CT and histological investigation demonstrated that β-E/PLGA composite scaffolds promoted new bone growth in the skull defect region of diabetic rats.Conclusion: Overall, these findings suggest that the β-E/PLGA composite scaffolds promote the healing of bone defects in diabetic rats. The combination of β-ecdysone and tissue-engineered scaffolds presents a promising approach for treating diabetes-related bone defects.
研究领域:
生物医学工程
·
内分泌学
·
组织工程学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-18
·
IF 16.6
Li Zixin,He Danqing,Guo Bowen,Wang Zekun,Yu Huajie,Wang Yu,Jin Shanshan,Yu Min,Zhu Lisha,Chen Liyuan,Ding Chengye,Wu Xiaolan,Wu Tianhao,Gong Shiqiang,Mao Jing,Zhou Yanheng,Luo Dan,Liu Yan
Infected bone defects are a major challenge in orthopedic treatment. Native bone tissue possesses an endogenous electroactive interface that induces stem cell differentiation and inhibits bacterial adhesion and activity. However, traditional bone substitutes have difficulty in reconstructing the electrical environment of bone. In this study, we develop a self-promoted electroactive mineralized scaffold (sp-EMS) that generates weak currents via spontaneous electrochemical reactions to activate voltage-gated Ca 2+ channels, enhance adenosine triphosphate-induced actin remodeling, and ultimately achieve osteogenic differentiation of mesenchymal stem cells by activating the BMP2/Smad5 pathway. Furthermore, we show that the electroactive interface provided by the sp-EMS inhibits bacterial adhesion and activity via electrochemical products and concomitantly generated reactive oxygen species. We find that the osteogenic and antibacterial dual functions of the sp-EMS depend on its self-promoting electrical stimulation. We demonstrate that in vivo, the sp-EMS achieves complete or nearly complete in situ infected bone healing, from a rat calvarial defect model with single bacterial infection, to a rabbit open alveolar bone defect model and a beagle dog vertical bone defect model with the complex oral bacterial microenvironment. This translational study demonstrates that the electroactive bone graft presents a promising therapeutic platform for complex defect repair.
研究领域:
骨科
·
生物材料
·
组织工程
·
再生医学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-18
·
IF 14.7
Yang Jirong,Chen Zhigang,Gao Chongjian,Liu Juan,Liu Kaizheng,Wang Xiao,Pan Xiaoling,Wang Guocheng,Sang Hongxun,Pan Haobo,Liu Wenguang,Ruan Changshun
Bioprinting that can synchronously deposit cells and biomaterials has lent fresh impetus to the field of tissue regeneration. However, the unavoidable occurrence of cell damage during fabrication process and intrinsically poor mechanical stability of bioprinted cell-laden scaffolds severely restrict their utilization. As such, on basis of heart-inspired hollow hydrogel-based scaffolds (HHSs), a mechanical-assisted post-bioprinting strategy is proposed to load cells into HHSs in a rapid, uniform, precise and friendly manner. HHSs show mechanical responsiveness to load cells within 4 s, a 13-fold increase in cell number, and partitioned loading of two types of cells compared with those under static conditions. As a proof of concept, HHSs with the loading cells show an enhanced regenerative capability in repair of the critical-sized segmental and osteoporotic bone defects in vivo. We expect that this post-bioprinting strategy can provide a universal, efficient, and promising way to promote cell-based regenerative therapy.
研究领域:
组织工程
·
再生医学
·
生物医学工程
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Yiping Weng,Xiuchen Yuan,Shijie Fan,Weihao Duan,Yadong Tan,Ruikai Zhou,Jingbin Wu,Yifei Shen,Zhonghua Zhang,Hua Xu
The treatment of various large bone defects has remained a challenge for orthopedic surgeons for a long time. Recent research indicates that curculigoside (CUR) extracted from the curculigo plant exerts a positive influence on bone formation, contributing to fracture healing. In this study, we employed emulsification/solvent evaporation techniques to successfully fabricate poly(ε-caprolactone) nanoparticles loaded with curculigoside (CUR@PM). Subsequently, using three-dimensional (3D) printing technology, we successfully developed a bioinspired composite scaffold named HA/GEL/SA/CUR@PM (HGSC), chemically cross-linked with calcium chloride, to ensure scaffold stability. Further characterization of the scaffold’s physical and chemical properties revealed uniform pore size, good hydrophilicity, and appropriate mechanical properties while achieving sustained drug release for up to 12 days. In vitro experiments demonstrated the nontoxicity, good biocompatibility, and cell proliferative properties of HGSC. Through alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, cell migration assays, tube formation assays, and detection of angiogenic and osteogenic gene proteins, we confirmed the HGSC composite scaffold’s significant angiogenic and osteoinductive capabilities. Eight weeks postimplantation in rat cranial defects, Micro-computed tomography (CT) and histological observations revealed pronounced angiogenesis and new bone growth in areas treated with the HGSC composite scaffold. These findings underscore the scaffold’s exceptional angiogenic and osteogenic properties, providing a solid theoretical basis for clinical bone repair and demonstrating its potential in promoting vascularization and bone regeneration.
研究领域:
生物医学工程
·
组织工程
·
骨科
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Qingsong Jiang,Liaomin Zhou,Yi Yang,Hu Long,Liming Ge,Defu Li,Changdao Mu,Wenli Lai,Zhilang Xu,Yan Wang
The structural and functional repair of critical-sized irregular bone defect is still considered a serious challenge. Most bone implant materials used in current clinic are not able to induce reconstruction of functional neural network, which is the key in bone regeneration via neural-osteogenic pathway. In this study, we aimed to manufacture a novel injectable double-crosslinked collagen/hyaluronic acid hydrogel loaded with nerve growth factor (NGF), which was capable of well filling irregularly shaped bone defects and inducing reconstruction of neural network. Hyaluronic acid (HA) was sequentially oxidized by sodium periodate and modified by methacrylic anhydride to prepare methacrylated oxidized HA (MOH) as a crosslinker. Subsequently, the Collagen-MOH@NGF (CMHN) hydrogel was established by Schiff base reaction and double-bond photocrosslinking. Our results demonstrated the excellent microporous structure, injectable, self-healing, in-situ rapid crosslinking properties of CMHN hydrogel along with suitable mechanics, rheology, swelling, degradation and biocompatibility. Significantly, the introduction of NGF endowed CMHN hydrogel with better biological properties than that without NGF. In vitro , CMHN hydrogel promoted DRG neuron growth and osteogenic differentiation of BMSCs mediated by NGF-calcitonin gene-related peptide (CGRP) axis. In vivo , CMHN hydrogel possessed a better bone repair effect than free NGF and blank hydrogel, with a long-lasting NGF-promoting neuro-osteogenic action within 8 w in a rat cranial critical defect model. Overall, the prepared injectable NGF-loaded collagen/HA dual network hydrogel is a promising material to facilitate functional and structural repair of complex bone defects.
研究领域:
生物材料
·
组织工程
·
再生医学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Zhengwei Liu,Hui Zhang,Jingjing Gan,Yuanjin Zhao,Yongxiang Wang
Hydrogel-derived implants have proven value in bone tissue regeneration, and current efforts have concentrated on devising strategies for producing functional implants with desired structures and functions to improve therapeutic outcomes. Herein, a novel black phosphorus (BP) tagged responsive strontium (Sr) hydrogel particles are presented for bone defect repair. By applying microfluidic technology, Sr and carboxymethyl chitosan, and BP are integrated into poly(N-isopropyl acrylamide) (pNIPAM) hydrogel matrix to generate such microparticles called pNBCSMs. Upon exposure to near-infrared irradiation, the pNBCSMs experience volume shrinkage and provoke the extrusion of the incorporated Sr, ascribed to the photothermal conversion ability of BP and the thermosensitivity of pNIPAM. In vitro and in vivo experimental results reveal that pNBCSMs subjected to near-infrared light display superior anti-inflammatory, anti-apoptotic, bacterial inhibitory, as well as osteogenesis-promoting effects, thereby effectively improving defective cranial bone repair. These features suggest that the proposed pNBCSMs can be promising candidates for bone repair.
研究领域:
生物材料学
·
组织工程学
·
医学
✓ 已验证
DOI
PubMed
高影响因子
Biomedicines
·
2023
·Vol. 11
·期 12
·3291
·
IF 4.7
Jingjing Sun,Wei Chen,Zheng Zhou,Xin Chen,You Zuo,Jiaqian He,Hairong Liu
(1) Background: Osteoarthritis (OA) is a crippling condition characterized by chondrocyte dedifferentiation, cartilage degradation, and subsequent cartilage defects. Unfortunately, there is a lack of effective medicines to facilitate the repair of cartilage defects in OA patients. In this study, we investigated the role of lncRNA NEAT1_2 in maintaining the chondrocyte phenotype and identified tanshinone IIA(TAN) as a natural medicine that enhances NEAT1_2 levels, resulting in efficient cartilage regeneration under inflammatory cytokines. (2) Methods: The transcriptional levels of NEAT1_2 and cartilage phenotype-related genes were identified by RT-qPCR. The siRNA interference approach was utilized to silence NEAT1_2; the Alamar Blue assay was performed to determine chondrocyte viability under inflammatory conditions. To evaluate the concentrations of collagen type II and glycosaminoglycans distributed by chondrocytes in vitro and in vivo, immunohistochemical staining and Safranin O staining were used. (3) Results: IL-1β suppresses NEAT1_2 and genes related to the chondrocytic phenotype, whereas TAN effectively upregulates them in a NEAT1_2-dependent manner. Consistently, TAN alleviated chondrocyte oxidative stress inhibited cartilage degradation by modulating the relevant genes and promoted efficient cartilage regeneration in vitro and in vivo when chondrocytes are exposed to inflammatory cytokines. (4) Conclusions: TAN enhances the expression of NEAT1_2 inhibited by IL-1β and affects the transcription of chondrocytic phenotype-related genes, which promotes cartilage regeneration in an inflammatory environment.Keywords:osteoarthritis;tanshinone IIA;NEAT1_2;cartilage defects repair;inflammatory
研究领域:
风湿病学
·
药理学
·
分子生物学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
npj Biofilms and Microbiomes
·
2025
·Vol. 11
·期 1
·1-16
·
IF 9.2
Mwangi Kevin H.,Qu Yue,Hu Peilun,Nagayasu Toshitatsu,Liu Jia-Feng,Wang Xiumei
Critical bone defects, exacerbated by infections, pose significant challenges to bone healing and homeostasis, necessitating the development of dual-functional biomimetics that combine anti-infective and reparative capabilities. The EGaIn holds promise across various disciplines, though its interactions with microbial cells require further elucidation. This investigation evaluates the antimicrobial efficacy of PEG-EGaIn nanocapsules against a spectrum of bacterial, employing electron microscopy. Constructs containing 1.5% PEG-EGaIn hinder biofilm-producing bacteria, while 3% concentrations amplify the biocidal effect. Furthermore, the nanocapsules promoted osteogenic differentiation rBMSCs, evidenced by enhanced mineralization and upregulation of key osteogenic genes. In addressing large bone defects, PEG-EGaIn-Col-Ap-lamellar and ethanolic-mediated Col-Ap-lamellar constructs serve as potential solutions for bone resorption mitigation and osteo-angiogenesis. Bone-remodeling were validated through μ-CT and histomorphometry confirming no evidence of chronic inflammation or fibrosis. In this study, PEG-EGaIn nanocapsules emerge as potent biocide and bone repair, underscoring their potential in combating antibiotic resistance and enhancing bone healing.
研究领域:
微生物学
·
生物医学工程
·
材料科学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomimetics
·
2022
·Vol. 7
·期 4
·227
·
IF 3.743
Zhengqiang Li,Xiaoxue Zheng,Yixing Wang,Tianyi Tao,Zilin Wang,Long Yuan,Bing Han
With the increase in population aging, the tendency of osteochondral injury will be accelerated, and repairing materials are increasingly needed for the optimization of the regenerative processes in bone and cartilage recovery. The local environment of the injury sites and the deficiency of Mg2+retards the repairing period via inhibiting the progenitor osteogenesis and chondrogenesis cells’ recruitment, proliferation, and differentiation, which results in the sluggish progress in the osteochondral repairing materials design. In this article, we elucidate the Mg2+-concentration specified effect on the cell proliferation, osteochondral gene expression, and differentiation of modeling chondrocytes (extracted from New Zealand white rabbit) and osteoblasts (MC3T3-E1). The concentration of Mg2+in the culture medium affects the proliferation, chondrogenesis, and osteogenesis: (i) Appropriate concentrations of Mg2+promote the proliferation of chondrocytes (1.25–10.0 mM) and MC3T3-E1 cells (2.5–30.0 mM); (ii) the optimal concentration of Mg2+that promotes the gene expression of noncalcified cartilage is 15 mM, calcified cartilage 10 mM, and subchondral bone 5 mM, respectively; (iii) overdosed Mg2+leads to the inhibition of cell activity for either chondrocytes (>20 mM) or osteoblasts (>30 mM). The biomimetic elucidation for orchestrating the allocation of gradient concentration of Mg2+in accordance of the physiological condition is crucial for designing the accurate microenvironment in osteochondral injury defects for optimization of bone and cartilage repairing materials in the future.Keywords:magnesium;chondrogenesis;osteogenesis;osteochondral defect;osteochondral unit
研究领域:
生物材料
·
再生医学
·
生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Afeng Miao,Qingsong Li,Genling Tang,Qifeng Lu
Bone defects persist as a significant challenge in the field of clinical orthopedics. This study focuses on the fabrication and characterization of 3D-printed composite hydrogel scaffolds composed of sodium alginate, gelatin, and α-tricalcium phosphate (α-TCP) with varying ratios of Strontium ions (Sr 2+ ). These scaffolds aim to address the clinical challenges associated with bone defect repair by providing mechanical support and promoting bone formation and vascularization. The degradation, swelling, mechanical properties, and release profiles of Sr 2+ from the hydrogel scaffolds were comprehensively characterized. In vitro tests were conducted to assess cell viability and proliferation, as well as osteogenic and angiogenic gene expression, to investigate the osteogenic and pro-angiogenic potential of the composite hydrogel scaffolds. Furthermore, skull defect simulations were performed, and composite scaffolds with varying Sr 2+ ratios were implanted to evaluate their effectiveness in bone repair. This research establishes a foundation for advancing bone tissue engineering through composite scaffolds containing biological macromolecules and strontium, with alginate serving as a key element in enhancing performance and expanding clinical applicability.
研究领域:
组织工程
·
骨科
·
生物材料
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2019
·
IF 8.013
Wentao Dang,Bing Ma,Zhiguang Huan,Rongcai Lin,Xiaoya Wang,Tian Li,JinFu Wu,Nan Ma,Haibo Zhu,Jiang Chang,Chengtie Wu
Bone tumors may lead to osteoporosis. It is of great significance to fabricate functional scaffolds for treating bone tumor, osteoporosis and repairing bone defects. In this study, LaB 6 micro-nanoparticles/poly( d , l -lactide)-modified β-tricalcium phosphate scaffolds (TCP-PDLLA-LB) were successfully prepared. The LaB 6 surface chemistry-reinforced TCP-PDLLA-LB scaffolds were endowed with the following excellent properties: (1) the enhanced mechanical strength. The TCP-PDLLA-5LB scaffolds possessed higher compression resistant capacity than TCP scaffolds owing to the strong adhesive property of PDLLA that bound the LaB 6 micro-nanoparticles and scaffolds tightly; (2) the excellent photothermal performance. TCP-PDLLA-LB scaffolds presented distinct photothermal property because of localized surface plasmon resonance effect of LaB 6 micro-nanoparticles when exposed to the near-infrared (NIR) light (wavelength: 808 nm) and it was flexibly controllable through changing the quantity of LaB 6 micro-nanoparticles, power density of NIR light and environmental humidity; (3) the excellent biological properties in vitro . When culturing with saos-2 bone tumor cells, the TCP-PDLLA-5LB scaffolds effectively killed the saos-2 cells through adjusting power density of NIR light, irradiation duration time of NIR light and irradiation times of NIR light. Additionally, the TCP-PDLLA-5LB scaffolds were able to release bioactive ions which were beneficial to the in vitro osteogenesis of rabbit bone marrow stromal cells (rBMSCs) by supporting the attachment and proliferation of rBMSCs as well as promoting the expressions of osteogenic genes BMP2, RUNX2 and COL 1; and (4) the abilities of effectively ablating bone tumors and supporting bone tissue regeneration in vivo . The bone tumor tissues were significantly ablated and suppressed through hyperthermia due to the existence of LaB 6 micro-nanoparticles on the scaffolds. Simultaneously, TCP-PDLLA-5LB scaffolds implanted in bone defects effectively helped new bone formation regardless of NIR light irradiation. In conclusion, LaB 6 surface chemistry-reinforced scaffolds possess the dual functions of ablating bone tumor and repairing bone defects, which offers a promising therapy strategy for tumor/disease-related bone tissue engineering.
研究领域:
生物医学工程
·
材料科学
·
肿瘤学
✓ 已验证
DOI
高影响因子
Journal of Orthopaedic Translation
·
2024
·
IF 5.9
Peng He,Yanbin Zhao,Bin Wang,Guoyin Liu,Lei Zhang,Mei Li,Bin Xu,Weihua Cai,Chenglin Chu,Yu Cong
Background The repair of bone defects has always been a significant challenge in clinical medicine. To address this challenge, doctors often utilize autologous bone grafts, allogeneic bone grafts and artificial bone substitutes. However, the former two methods may result in additional trauma and complications, while allogeneic bone grafts carry the risks of immune rejection and disease transmission. Magnesium phosphate cement (MPC), as a artificial bone substitutes, has been a potential biomaterial for repairing bone defects, but its clinical application is limited by insufficient mechanical strength and poor osteoinductive activity. Methods In this study, the cement liquid phase base on rhBMP-2 and chitosan solution into MPC were obtained and investigated. After mixing with a cement liquid, the structural and phase composition, morphology, chemical structure, setting time, compressive strength, degradation behavior, solubility, and cellular responses and bone regeneration in response to CHI-rhBMP2 MPC were investigated in vitro and in vivo. Results After the chemical component modification, CHI-rhBMP2 MPC possessed controllable degradation rate, moderate setting time, appropriate cuing temperature, good injectability, and improved initial strength. In vitro tests showed that the CHIrhBMP2 MPC could promote cell proliferation and adhesion, as well as that contribute to osteoblast differentiation and mineralization. In addition, cement materials were implanted into the rabbit femoral condyles for in vivo osseointegration evaluation. The results displayed that more new bone grew around CHI-rhBMP2 MPC, verifying improved osseointegration capacity. Transcriptome analysis revealed that focal adhesion, Forkhead box O（FoxO） signaling pathway and P13K/AKT signaling pathway were may involved in CHI-rhBMP2 MPC induced new bone formation. Conclusion This work provides a new strategy for the rational design of potential bone repair candidate materials.
研究领域:
生物材料学
·
骨科医学
·
组织工程学
✓ 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）