Frontiers in Bioengineering and Biotechnology
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2026
·
IF 5.8
Yuan Fan,Haiyan Yao,Junchao Wei,Yipeng Hu
Titanium (Ti) implants are widely used in bone defect repair, however, postoperative infections and insufficient osseointegration would lead to implant failure. Therefore, it is much critical and necessary to construct antibacterial and osteogenic coatings on the surface of Ti implants to improve the successful rate of operation. Herein, D-penicillamine stabilized chiral ZnO nanoparticles (D-ZnO NPs) were prepared, which were loaded on the surface of Ti implants together with BMP-2 to construct a dual functional coating with antibacterial and osteogenic properties. The in vitro results demonstrated that the coating showed excellent antibacterial ability, and the antibacterial rates against S. mutans , E. coli and S. aureus were 86%, 98%, and 76%, respectively. Additionally, the coating could effectively induce macrophage polarization towards M2 phenotype, which modulated the local immune microenvironment. Furthermore, the introduction of bone morphogenetic protein-2 (BMP-2) promoted osteogenesis, which may enhance the osseointegration of Ti implants. This study provides a novel strategy to address the challenges of Ti implants, and offer the solid theoretical foundation for expanding the clinical applications of multifunctional Ti implants materials.
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高影响因子
Scientific Reports
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2017
·Vol. 7
·期 1
·1-13
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IF 4.259
Fu Chuan,Yang Xiaoyu,Tan Shulian,Song Liangsong
Lack of bioactivity has seriously restricted the development of biodegradable implants for bone tissue engineering. Therefore, surface modification of the composite is crucial to improve the osteointegration for bone regeneration. Bone morphogenetic protein-2 (BMP-2), a key factor in inducing osteogenesis and promoting bone regeneration, has been widely used in various clinical therapeutic trials. In this study, BMP-2 was successfully immobilized on graphene oxide-incorporated PLGA/HA (GO-PLGA/HA) biodegradable microcarriers. Our study demonstrated that the graphene oxide (GO) facilitated the simple and highly efficient immobilization of peptides on PLGA/HA microcarriers within 120 min. To further test in vitro , MC3T3-E1 cells were cultured on different microcarriers to observe various cellular activities. It was found that GO and HA significantly enhanced cell adhesion and proliferation. More importantly, the immobilization of BMP-2 onto the GO-PLGA/HA microcarriers resulted in significantly greater osteogenic differentiation of cells in vitro , as indicated by the alkaline phosphate activity test, quantitative real-time polymerase chain reaction analysis, immunofluorescence staining and mineralization on the deposited substrates. Findings from this study revealed that the method to use GO-PLGA/HA microcarriers for immobilizing BMP-2 has a great potential for the enhancement of the osseointegration of bone implants.
研究领域:
生物医学工程
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组织工程
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骨再生
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材料科学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Shang Wang,Huan Lei,Yu Mi,Pei Ma,Daidi Fan
In bone defects, infections lead to excessive inflammation, increased bacterial, and bone lysis, resulting in irregular wounds that hinder new bone regeneration. Injectable bioactive materials with adequate antimicrobial activity and strong osteogenic potential are urgently required to remedy irregular defects, eradicate bacteria, and facilitate the generation of new bone tissue. In this research, injectable dual-network composite hydrogels consisting of sulfated chitosan, oxidized hyaluronic acid, β-sodium glycerophosphate, and Cu Sr doped mesoporous bioactive glass loaded with bone morphogenetic protein (CuSrMBG BMP-2 ) were utilized for the first time to treat infectious bone defects. Initially, the hydrogel was injected into the wound at 37 °C with minimal invasion to establish a stable state and prevent hydrogel loss. Subsequently, sulfated chitosan eliminated bacteria at the wound site and facilitated cell proliferation with oxidized hyaluronic acid. Additionally, CuSrMBG BMP-2 strengthened antibacterial properties, regulated inflammatory reactions, promoted angiogenesis and osteogenic differentiation, addressing the deficiency in late-stage osteogenesis. Specifically, the injectable dual-network hydrogel based on chitosan and hyaluronic acid is minimally invasive, offering antibacterial, anti-inflammatory, pro-angiogenic, and bone regeneration properties. Therefore, this hydrogel with injectable dual network properties holds great promise for the treatment of bone infections in the future.
研究领域:
生物材料
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组织工程
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骨科
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生物医学工程
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Clinical Oral Investigations
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2026
·Vol. 30
·期 5
·213
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IF 3.6
Yang Zhenyu,Yang Mengyao,Ye Jiaxue,Lei Xiaoyue,Huo Xiaodan,Qin Zirui,Qi Linlong,Chen Yiduo,Wang Yuan,Deng Shuli
Objectives Pulp necrosis in immature permanent teeth arrests root development and compromises long-term prognosis. This study aimed to develop a multifunctional scaffold integrating structural biomimicry, mechanical matching, and sustained growth factor release for orderly root regeneration. Materials and methods A poly(ε-caprolactone) (PCL) conical scaffold was fabricated via melt electrowriting (MEW) combined with mechanical winding. Bone morphogenetic protein‑2 (BMP‑2)-loaded microspheres were prepared and physically incorporated into the scaffold. The scaffold surface was modified with collagen. Human dental pulp stem cells (hDPSCs) were cultured on the scaffold to evaluate proliferation, adhesion, and osteogenic differentiation. Results The scaffold exhibited a trilayer “collagen–microsphere–PCL” architecture with mechanical compatibility (elastic modulus: 22.5 MPa; fracture strength: 5.29 MPa; elongation: 441.59%). Microspheres (2.86 ± 0.45 μm) showed a gradient distribution and sustained release (70–75% over 90 days). In vitro, the scaffold promoted hDPSC adhesion and proliferation and significantly enhanced osteogenic differentiation with elevated alkaline phosphatase activity, upregulated the expression of osteogenic-related genes, and increased protein levels. Conclusions The scaffold integrates structural support, controlled growth factor delivery, and a bioactive interface, offering a promising strategy for root development in immature permanent teeth. Clinical relevance By enabling physiological root development, the scaffold addresses a critical unmet need, offering a viable alternative to conventional root canal therapy.
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American Journal of Translational Research
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2018
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IF 3.061
Qian Tang,Minji Tong,Gang Zheng,Liyan Shen,Ping Shang,Haixiao Liu
The Masquelet’s induced membrane (IM) technique is widely used to treat large segmental bone defects due to its physical priority and biological function. However, the underlying molecular mechanism of the IM on bone formation remains unknown. In the present study, rat bone marrow-derived mesenchymal stem cells (BMSCs) were used as an in vitro model and bone morphogenetic protein 2 (BMP-2) was used as a positive control to evaluate the effects of the IM on the osteogenic differentiation of BMSCs. Although the IM group did not exhibit a significant increase in the expression of Runt-related transcription factor 2 (Runx2), Collagen I (Col I), osteocalcin (OCN) and alkaline phosphatase (ALP) relative to the BMP-2 administration, the IM was considerably effective compared with the untreated group. Mechanistically, we found that the IM activated the Smad and mitogen-activated protein kinase (MAPK) pathways, which was further confirmed by application of specific inhibitors of Smad1/5/8 (LDN-193189) and ERK1/2 (U0126). After the combined treatment of the IM and LDN-193189 as well as U0126, the IM-induced increase in Runx2, Col I, and OCN expression was significantly inhibited. These results suggest that IM promotes the osteogenic differentiation of rat BMSCs by activating the Smad1/5/8 and MAPK pathways.
研究领域:
骨科
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干细胞生物学
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分子生物学
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JOURNAL OF APPLIED POLYMER SCIENCE
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2024
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IF 2.7
Zhenxu Wu,Guoqing Niu,Zongtai Xiong,Xinxiang Ding,Yongbo Li,Peibiao Zhang,Feng Wu
Deer bone in traditional Chinese medicine is valued for its unique biomimetic bone matrix components. Icariin (Ica), which is claimed by Chinese medicine as a bone-repairing agent, is also widely accepted. In this report, a novel Ica-encapsulated PLGA/nano deer bone meal (Ica@PLGA/nBM) biomimetic microsphere was fabricated. The Ica could be released from microspheres in a controlled manner. In vitro results showed that the microsphere had good biocompatibility due to the addition of nBM and the MC3T3-E1 cells could adhere to and grow well on the microspheres. Moreover, Ica and nBM in microspheres could synergically promote the ALP activity of MC3T3-E1 cells significantly ( p < 0.05), which indicated the acceleration of osteogenic differentiation. The RT-PCR results showed that the expression levels of bone matrix proteins (Col1 & OPN) were enhanced by the composite ( p < 0.05). In addition, Ica and nBM in microspheres also obviously promoted the expression of RUNX2 and BMP-2, respectively ( p < 0.05). The in vivo results demonstrated the effective promotion of Ica@PLGA/nBM on complete bony connection to cover the defect site and the bone defect repair. And the Ica(M)@PLGA/nBM microspheres provided the best repair results. All the results confirmed that the Ica@PLGA/nBM composite biomimetic microsphere has the potential for clinical application.
研究领域:
材料科学
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生物医学工程
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药理学
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组织工程
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2021
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IF 6.953
Bo Wang,Shuai Yuan,Wei Xin,Yi Chen,Qiwei Fu,Lexiang Li,Yang Jiao
Bone defect repair and tissue engineering is specifically challenging process because of the distinctive morphological and structural behaviours of natural bone with complex healing and biochemical mechanisms . In the present investigation, we designed dopamine adhesive chemistry-based fabrication of silk fibroin hydrogel (SFD) with incorporation of nano-hydroxyapatite (nHA)-graphene oxide (GO) hybrid nanofillers with well-arranged porous morphology immobilized with bone morphogenic protein-2 (BMP-2) for the effective in vitro rabbit bone marrow derived mesenchymal stem cells loading compatibility and in vivo new bone regrowth and collagen deposition ability. We have achieved bone-specific hydrogel scaffolds with upgraded structural features, mechanical properties and particularly promoted in vitro osteogenic differentiation and compatibility of rabbit bone marrow mesenchymal stem cells (rBMSCs). Structural and microscopic analyses established greater distributions of components and well-ordered and aligned porous structure of the hydrogel network. In vivo result of new bone regrowth was promisingly higher in the Bm@nHG-SFD hydrogel (85%) group as compared to the other treatment groups of nHG-SFD (77%) and nH-SFD (64%) hydrogel. Overall, we summarized that morphologically improved hydrogel material with immobilization of BMP-2 could be have more attentions for new generation bone regeneration therapies.
研究领域:
生物材料学
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组织工程学
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再生医学
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Biomaterials Science
·
2019
·Vol. 7
·期 9
·3614-3626
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IF 5.251
Yihong Gong,Yiling Zhang,Zhinan Cao,Feng Ye,Zefeng Lin,Yan Li
Injectable scaffolds have attracted much attention because of their minimum surgical invasiveness. However, limited osteogenic induction property and low mechanical properties hampered their application in bone tissue engineering. CaCO3 microspheres, which possess osteoinductivity, rough surfaces and specific binding sites for BMP-2, were first fabricated; after BMP-2 uploading, microspheres were further entrapped in fibrin-glue hydrogel. CaCO3 microspheres were co-functionalized with casein and heparin. To obtain a high encapsulation of heparin and thus BMP-2 uploading, along with controlled release and simultaneous maintenance of the presence of vaterite which had osteogenic induction property, fabrication parameters were optimized and microspheres were characterized using XRD, FITR and SEM. The formed CaCO3 had a microsphere morphology of ∼1 μm. Both vaterite and calcite phases were present and the relative amount of calcite phase increased with the amount of heparin. Sample 25 mM_4-1Hep with the highest loading amount of heparin was selected as carrier for BMP-2 and BMP-2 loaded CaCO3 microspheres were further entrapped in fibrin-glue hydrogel (FC-B). For the as-prepared composite hydrogel, mechanical properties were characterized and the presence of CaCO3 significantly elevated the tensile strength; controlled release of BMP-2 was sustained until day 21. Based on ALP activity, alizarin red staining and RT-PCR, in vitro osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was found to be significantly enhanced under induction of FC-B. Rabbit tibia bone defect model was applied to evaluate its in vivo performance. After implantation for 4 weeks, presence of composite hydrogel was observed in defects. After 8 weeks, bone defects of FC-B group were nearly completely healed. Using the fact that autologous scaffolds can be derived based on fibrin-glue hydrogel, the well-designed BMP-2 loaded fibrin-glue composite hydrogel demonstrated good potential in bone tissue engineering.
研究领域:
组织工程
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生物材料
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骨再生
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药物递送系统
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Bioactive Materials
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2022
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IF 16.874
Qinghao Zhang,Yuanda Liu,Jie Li,Jing Wang,Changsheng Liu
Exposure to a growth factor abundant milieu has remarkable regenerative and rejuvenating effects on organ diseases, tissue damage, and regeneration, including skeletal system defects and bone regeneration. Although the introduction of candidate growth factors into relevant fields has been reported, their regenerative effects remain unsatisfactory, mainly because of the experimental challenges with limited types of growth factors, elusive dosage adjustment, and asynchronous stem cell activation with cytokine secretion. Here, an innovative hydrogel recapitulating a growth factor-enriched microenvironment (GEM) for regenerative advantage, is reported. This sulfated hydrogel includes bone morphogenetic protein-2 (BMP-2), an essential growth factor in osteogenesis, to direct mesenchymal stem cell (MSC) differentiation, stimulate cell proliferation, and improve bone formation. The semi-synthetic hydrogel, sulfonated gelatin (S-Gelatin), can amplify BMP-2 signaling in mouse MSCs by enhancing the binding between BMP-2 and BMP-2 type II receptors (BMPR2), which are located on MSC nuclei and activated by the hydrogel. Importantly, the dramatically improved cytokine secretion of MSCs throughout regeneration confirms the growth factor-acquiring potential of S-Gelatin/rhBMP-2 hydrogel, leading to the vascularization enhancement. These findings provide a new strategy to achieve an in situ GEM and accelerated bone regeneration by amplifying the regenerative capacity of rhBMP-2 and capturing endogenous growth factors.
研究领域:
再生医学
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组织工程学
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生物材料科学
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骨骼生物学
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Advanced Healthcare Materials
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2022
·Vol. 12
·期 1
·2201661
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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
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再生医学
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免疫学
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生物医学工程
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骨生物学
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
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2021
·Vol. 110
·期 5
·1178-1191
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IF 3.368
Limei Li,Jidong Li,Qin Zou,Yi Zuo,Lili Lin,Bin Cai,Yubao Li
The interconnectivity of porous scaffold is vital for cell and tissue infiltration, and vascular networks formation, determining the successful bone regeneration in large bone defects. Here, inspired by the lotus-root and Haversian system of natural bone, a nano-hydroxyapatite/polyurethane (n-HA/PU) lotus root-like scaffold inlaid with micro holes on the wall of the adjacent channel was utilized to mediate cell biomineralization and vascularized bone tissue regeneration. Such a particular lotus-type structure remarkably promoted cells to proliferate and infiltrate into the center of the entire scaffold, serving as a clue to account for regulating cell alignment and differentiation physically. In vitro studies suggested that apatite accumulated dramatically on the channel wall in the lotus-type scaffold, probably promoting specific osteogenic differentiation of cells by the orientated channels, even in the absence of osteogenic factors. In vivo creation of critical bone defects (15-mm segments) was done in the radius of rabbits and implanted with the scaffold of different geometry to assess the structural parameters on the efficacy of new bone regeneration. The more extensive positive staining of BMP-2, more considerable amount of infiltrated capillary, more robust new bone formation, particularly the biomechanical strength of lotus-type scaffold group could reach the level of the control group without surgery, indicating that the lotus-type scaffold was more favorable for new bone tissue formation along tube-like channels. These results highlighted the potential of this biomimetic scaffold for cell and tissue infiltration and thus repair large bony defects.
研究领域:
组织工程
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生物医用材料
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再生医学
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骨科
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高影响因子
Acta Biomaterialia
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2024
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IF 9.4
Jintao Zhong,Wenhua Li,Hetong Li,Jin Zhang,Zuoxu Hou,Xiao Wang,Enhui Zhou,Ke Lu,Weida Zhuang,Hongxun Sang
The periosteum, a highly specialized thin tissue, is instrumental in contributing to as much as 70% of early bone formation. Recognizing the periosteum's vital physiological roles, the fabrication of a biomimetic periosteum has risen as an auspicious strategy for addressing extensive bone defects. In the study, we obtained such biomimetic periosteum by utilizing periosteum-derived stem cells (PDSCs) spheroids. These spheroids are induced to spontaneously generate a bioactive membrane on a delicate 3D-printed polycaprolactone (PCL) substrate. This process yields a biomimetic periosteum rich in the resources needed for bone repair. The in vitro evaluations demonstrated that this membrane can act as a repository for growth factors and stem cells. The release kinetics confirmed a sustained delivery of BMP-2 and VEGF, which promoted enhanced osteogenesis and angiogenesis in vitro , respectively. The in vivo results further highlighted robust bone regeneration from critical cranial defects upon the application of this biomimetic periosteum. The biomimetic periosteum, easily harvested and potent in bioactivity, presents substantial clinical potential, particularly for the treatment of critical-sized bone defects. Statement of Significance PDSC theoretically demonstrates substantial potential in membrane construction, a value we've harnessed in this pioneering application. By employing cell spheroids, we've successfully integrated a substantial number of cells into the membrane framework. PDSC spheroids exhibit the remarkable ability to self-assemble into functional membranes, endowing them with robust biological capabilities that enhance their performance in biological systems. The in vitro evaluations demonstrated that this membrane can act as a repository for growth factors and stem cells. The in vivo bone repair facilitated by this membrane is notably effective, characterized by superior bone quality and accelerated formation rates. This process mirrors the natural intramembrane ossification, offering a promising approach to bone integration and regeneration.
研究领域:
组织工程
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再生医学
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骨生物学
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干细胞研究
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高影响因子
危险品化学品经营许可证（带存储）