MOLECULES
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2019
·Vol. 24
·期 9
·1669
·
IF 3.06
Yidi Zhang,Chong Wang,Li Fu,Shan Ye,Min Wang,Yanmin Zhou
Osteogenic peptides have been reported as highly effective in directing mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo. Therefore, developing novel biomaterials for the controlled delivery of osteogenic peptides in scaffolds without lowering the peptide’s biological activity is highly desirable. To repair a critical-sized bone defect to efficiently achieve personalized bone regeneration, a novel bioactive poly(lactic-co-glycolic acid) (PLGA)/β-tricalcium phosphate (β-TCP) composite scaffold, in which graphene oxide (GO) and bone morphogenetic protein (BMP)-2-like peptide were loaded in situ (PTG/P), was produced by an original cryogenic 3D printing method. The scaffolds were mechanically comparable to human cancellous bone and hierarchically porous. The incorporation of GO further improved the scaffold wettability and mechanical strength. The in situ loaded peptides retained a high level of biological activity for an extended time, and the loading of GO in the scaffold further tuned the peptide release so that it was more sustained. Our in vitro study showed that the PTG/P scaffold promoted rat bone marrow-derived mesenchymal stem cell ingrowth into the scaffold and enhanced osteogenic differentiation. Moreover, the in vivo study indicated that the novel PTG/P scaffold with sustained delivery of the peptide could significantly promote bone regeneration in a critical bone defect. Thus, the novel bioactive PTG/P scaffold with a customized shape, improved mechanical strength, sustainable peptide delivery, and excellent osteogenic ability has great potential in bone tissue regeneration.Keywords:osteogenic peptide;sustained delivery;bone tissue engineering;scaffolds;graphene oxide
研究领域:
生物医学工程
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材料科学
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组织工程
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 10
·1878-1890
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IF 4.872
Anxiu Xu,Liwei Zhou,Yi Deng,Xianshen Chen,Xiaoling Xiong,Feng Deng,Shicheng Wei
Carbon fiber-reinforced polyetheretherketone (CFRPEEK) possesses biomechanical properties such as elastic modulus similar to human bones and is becoming a dominant alternative to replace the traditional metallic implants. The defective osseointegration and bacterial infection risk of CFRPEEK, however, impede its clinical adoption. In the current study, a newly-developed carbon fiber-reinforced polyetheretherketone/nanohydroxyapatite (CFRPEEK/n-HA) ternary biocomposite was functionalized by covalently grafting carboxymethyl chitosan (CMC) followed by the decoration of a bone-forming peptide (BFP) assisted via the polydopamine tag strategy. Antibacterial test with Staphylococcus aureus (S. aureus) indicated that the CMC and peptide-conjugated substrates (pep-CMC-CFRPEEK/n-HA) significantly suppressed bacterial adhesion. In vitro cell attachment/growth, spreading assay, alkaline phosphatase activity, real-time PCR analysis, osteogenesis-related protein expression and calcium mineral deposition all disclosed greatly accelerated adhesion, proliferation and osteo-differentiation of human mesenchymal stem cells (hMSCs) on the pep-CMC-CFRPEEK/n-HA biocomposite due to the additive effect of the CMC polysaccharide and the small osteoinductive peptide. More importantly, in vivo evaluation of the beagle tibia model by means of micro-CT, histological analysis, SEM observation and fluorescent labeling confirmed the remarkably boosted bioactivity and osteointegration. The CFRPEEK/n-HA ternary composite with the dual functions of bacterial adhesion reduction and osteointegration promotion holds great potential as a bioactive implant material in orthopedic/dental applications based on this scheme.
研究领域:
生物医学工程
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材料科学
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骨科/牙科植入物研究
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产品关联
DOI
PubMed
高影响因子
Biofabrication
·
2020
·Vol. 12
·期 3
·035004
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IF 8.213
Chong Wang,Xinyu Ye,Yitao Zhao,Lu Bai,Zhi He,Qing Tong,Xiaoqiong Xie,Huangrong Zhu,Daozhang Cai,Yun Zhou,Bingheng Lu,Yen Wei,Lin Mei,Denghui Xie,Min Wang
Tumor resection is widely used to prevent tumor growth. However, the defected tissue at the original tumor site also causes tissue or organ dysfunction which lowers the patient's life quality. Therefore, regenerating the tissue and preventing tumor recurrence are highly important. Herein, according to the concept of 'first kill and then regenerate', a versatile scaffold-based tissue engineering strategy based on cryogenic 3D printing of water-in-oil polyester emulsion inks, containing multiple functional agents, was developed, in order to realize the elimination of tumor cells with recurrence suppression and improved tissue regeneration sequentially. To illustrate our strategy, water/poly(lactic-co-glycolic acid)/dichloromethane emulsions containing β-tricalcium phosphate (β-TCP), 2D black phosphorus (BP) nanosheets, low-dose doxorubicin hydrochloride (DOX) and high-dose osteogenic peptide were cryogenically 3D printed into hierarchically porous and mechanically strong nanocomposite scaffolds, with multiple functions to treat bone tumor, resection-induced tissue defects. Prompt tumor ablation and long-term suppression of tumor recurrence could be achieved due to the synergistic effects of photothermotherapy and chemotherapy, and improved bone regeneration was obtained eventually due to the presence of bony environment and sustained peptide release. Notably, BP nanosheets in scaffolds significantly reduced the long-term toxicity phenomenon of released DOX during in vivo bone regeneration. Our study also provides insights for the design of multi-functional tissue engineering scaffolds for treating other tumor resection-induced tissue defects.
研究领域:
生物医学工程
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组织工程
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癌症治疗
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DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2025
·
IF 5.1
Jinpeng Gong,Boya Liu,Tao Huang,Lu Wei,Yupeng Ma,Hao Chen,Jing Gan,Junbo Ge
Osteoporosis, a prevalent metabolic bone disease, poses a significant challenge for bone repair in aged populations. Soy-derived osteogenic peptide (SOP) holds promise but its clinical translation is hampered by rapid enzymatic degradation and poor oral bioavailability, representing a major challenge that necessitates the development of a protective delivery system. To address this, we developed a novel composite hydrogel based on fish gelatin and sodium alginate (SA/FG) as an oral delivery vehicle to overcome these limitations. Systematic characterization revealed that the SA/FG formulation offers distinct advantages: the incorporation of an optimal amount of SA significantly enhanced the mechanical strength and stability of the hydrogel, addressing the common weakness of single-network gelatin hydrogels, while maintaining a high water content (~90%) and a superior rehydration capacity (83.65% in distilled water). In a glucocorticoid-induced zebrafish osteoporosis model, the SOP-loaded SA/FG hydrogel significantly increased skull bone mass by 120.17% and improved larval swimming behavior, markedly outperforming the free SOP group. This study presents the first report of an SA/FG composite hydrogel for effective oral delivery of an osteogenic peptide. The system demonstrates great potential as a functional food or supplement for preventing and treating osteoporosis, offering an innovative strategy to enhance peptide stability and bioavailability through a biocompatible, double-network carrier.
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DOI
PubMed
高影响因子
Bioactive Materials
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2020
·
IF 8.724
Chong Wang,Jiahui Lai,Kai Li,Shaokui Zhu,Bingheng Lu,Jia Liu,Yujin Tang,Yen Wei
Three-dimensional (3D) printing has been increasingly employed to produce advanced bone tissue engineering scaffolds with biomimetic structures and matched mechanical strengths, in order to induce improved bone regeneration in defects with a critical size. Given that the successful bone regeneration requires both excellent osteogenesis and vascularization, endowing scaffolds with both strong bone forming ability and favorable angiogenic potential would be highly desirable to induce improved bone regeneration with required vascularization. In this investigation, customized bone tissue engineering scaffolds with balanced osteoconductivity/osteoinductivity were produced via cryogenic 3D printing of β-tricalcium phosphate and osteogenic peptide (OP) containing water/poly(lactic- co -glycolic acid)/dichloromethane emulsion inks. The fabricated scaffolds had a hierarchically porous structure and were mechanically comparable to human cancellous bone. Angiogenic peptide (AP) containing collagen I hydrogel was then coated on scaffold surface to further provide scaffolds with angiogenic capability. A sequential release with a quick AP release and a slow but sustained OP release was obtained for the scaffolds. Both rat endothelial cells (ECs) and rat bone marrow derived mesenchymal stem cells (MSCs) showed high viability on scaffolds. Improved in vitro migration and angiogenesis of ECs were obtained for scaffolds delivered with AP while enhanced osteogenic differentiation was observed in scaffolds containing OP. The in vivo results showed that, toward scaffolds containing both AP and OP, the quick release of AP induced obvious angiogenesis in vivo , while the sustained OP release significantly improved the new bone formation. This study provides a facile method to produce dual-delivery scaffolds to achieve multiple functions.
研究领域:
生物医学工程
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组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
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2023
·
IF 8.8
Dongyang Zhu,Wuchao Ma,Meilian Yang,Shuzhen Cheng,Ling Zhang,Ming Du
This study prepared osteogenic peptides (OPs) from cod meat by hydrolysis and subsequently encapsulated them in nanoliposomes (NLP) to enhance bioaccessibility. The characterization, stability, controlled release behavior and bioactivity of OPs-loaded nanoliposomes (OPs-NLP) were investigated as well. The highest loading capacity (27.32%) was achieved in NLP loaded with 6 mg/mL of OPs. The particle size, zeta potential, and encapsulation efficiency of OPs-NLP were 70.59 nm, −11.98 mV, and 75.24%, respectively. The interaction between OPs and empty NLP was through hydrogen bonding and hydrophobic. The OPs-NLP showed the greatest stability during storage at 4 °C. The in vitro release profile of OPs from OPs-NLP fitted a one-level kinetic model best. The osteogenic activity of OPs was unaffected by NLP encapsulation, and the bioaccessibility of OPs was notably improved. These findings suggest that OPs-NLP has the potential to be used in functional foods.
研究领域:
药学
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食品科学
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生物技术
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产品关联
DOI
PubMed
高影响因子
Biofabrication
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2025
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IF 8
Ruoyu Li,Wenfeng Li,Yungshan Teng,Runze Li,Siyi Kong,Xin Chen,Haotian Luo,Danying Chen,Yuqing Guo,Yangqiao Qing,Hio Cheng leong,Bingyan Guo,Meihan Chen,Zixin Pan,Shushuo Zheng,Yihong Deng,Yang Cao,Chen Zhou,Xuenong Zou,Weicai Wang
Craniofacial bone defect healing in periodontitis patients with diabetes background has long been difficult due to increased blood glucose levels which cause overproduction of reactive oxygen species (ROS) and a low pH environment. These conditions negatively affect the function of macrophages, worsen inflammation and oxidative stress, and ultimately, hinder osteoblasts' bone repair potential. In this study, we for the first time found that ANXA1 expression in macrophages was reduced in a diabetic periodontitis environment, with the activation of the NLRP3/Caspase-1/GSDMD signaling pathway, and, eventually, increased macrophage pyroptosis. Next, we have developed a new GPPG intelligent hydrogel system which was ROS and pH responsive, and loaded with Ac2-26, an ANXA1 bioactive peptide, and osteogenic peptide OGP as well. We found that Ac2-26/OGP/GPPG can effectively reduce ROS, mitigates macrophage pyroptosis via the ANXA1/NLRP3/Caspase-1/GSDMD pathway and enhanced osteogenic differentiation. The effect of Ac2-26/OGP/GPPG in regulation of pyroptosis and bone defect repair was also further validated by animal experiments on periodontitis-induced tooth loss model in diabetic rats. To conclude, our study unveils the effect of ANXA1 on macrophage pyroptosis in periodontitis patients with diabetes, based on which we introduced a promising innovative hydrogel system for improvement of bone defects repair in diabetic periodontitis patients via targeting macrophage pyroptosis and enhancing osteogenic potential.
研究领域:
牙科学
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药理学
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生物医学工程
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免疫学
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组织工程
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产品关联
DOI
PubMed
高影响因子
Biofabrication
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2020
·Vol. 12
·期 2
·025030
·
IF 8.213
Chong Wang,Haibing Yue,Wei Huang,Xudong Lin,Xiaoqiong Xie,Zhi He,Xiao He,Sanbiao Liu,Lu Bai,Bingheng Lu,Yen Wei,Min Wang
Due to the increasing aging population and the high probability of sport injury among young people nowadays, it is of great demand to repair/regenerate diseased/defected osteochondral tissue. Given that osteochondral tissue mainly consists of a subchondral layer and a cartilage layer which are structurally heterogeneous and mechanically distinct, developing a biomimetic bi-phasic scaffold with excellent bonding strength to regenerate osteochondral tissue is highly desirable. Three-dimensional (3D) printing is advantageous in producing scaffolds with customized shape, designed structure/composition gradients and hence can be used to produce heterogeneous scaffolds for osteochondral tissue regeneration. In this study, bi-layered osteochondral scaffolds were developed through cryogenic 3D printing, in which osteogenic peptide/β-tricalcium phosphate/poly(lactic-co-glycolic acid) water-in-oil composite emulsions were printed into hierarchically porous subchondral layer while poly(D,L-lactic acid-co-trimethylene carbonate) water-in-oil emulsions were printed into thermal-responsive cartilage frame on top of the subchondral layer. The cartilage frame was further filled/dispensed with transforming growth factor-β1 loaded collagen I hydrogel to form the cartilage module. Although the continuously constructed osteochondral scaffolds had distinct microscopic morphologies and varied mechanical properties at the subchondral zone and cartilage zone at 37 °C, respectively, the two layers were closely bonded together, showing excellent shear strength and peeling strength. Rat bone marrow derived mesenchymal stem cells (rBMSCs) exhibited high viability and proliferation at both subchondral- and cartilage layer. Moreover, gradient rBMSC osteogenic/chondrogenic differentiation was obtained in the osteochondral scaffolds. This proof-of-concept study provides a facile way to produce integrated osteochondral scaffolds for concurrently directing rBMSC osteogenic/chondrogenic differentiation at different regions.
研究领域:
生物医学工程
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组织工程
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再生医学
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生物材料
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2020
·
IF 4.152
MingLi Xiang,Mengyuan Zhu,Zun Yang,Ping He,Jingjing Wei,Xiang Gao,Jinlin Song
The development of biomimetic bone graft materials for periodontal tissue engineering is a field of topical interest. In this study, we designed a dual-functionalized apatite nanocomposite, which could integrate multiple molecular cues for manipulating the fate of periodontal ligament stem cells (PDLSCs). Briefly, inspired by mussels, a biomimetic nanohydroxyapatite was fabricated using a polydopamine structure as a template (named as tHA) and then surface-modified with bone-forming peptide-1 (BFP-1) and vascular endothelial growth factor-mimicking peptide (QK) via a single step of catechol chemistry. Our study showed that the biofunctions of tethered peptides were not compromised on the surface of apatite nanoparticles. Because of the synergistic effect of BFP-1 and QK peptides, the dual-functionalized apatite nanocomposite showed improved cytocompatibility compared to controls. Moreover, it can boost the proliferation and osteogenic differentiation of PDLSCs, indicating excellent bioactivity of tHA–BFP/QK nanoparticles on cell fate decision. More importantly, animal experiments showed that dual-functionalized apatite nanocomposites could dramatically promote the regeneration of periodontal bone. It is concluded that our work provides an instructive insight into the design of biomimetic apatite nanocomposites, which holds a great potential for applications in periodontal bone repair.
研究领域:
组织工程学
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生物材料科学
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牙科材料
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再生医学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 30
·6056-6067
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IF 6.331
Qian Li,He Zhang,Jijia Pan,Binhong Teng,Ziqian Zeng,Yang Chen,Yu Hei,Siqi Zhang,Shicheng Wei,Yuhua Sun
Due to the ability to combine multiple osteogenic induction “cues” at the same time, hydrogels are widely used in the three-dimensional (3D) culture of human mesenchymal stem cells (hMSCs) and osteoinduction. However, the survival and proliferation of stem cells in a 3D culture system are limited, which reduces their osteogenic differentiation efficiency. In addition, the cells inside the hydrogel are prone to apoptosis due to hypoxia, which is a serious challenge for tissue engineering based on stem cells. In this study, a tripeptide-based macroporous alginate hydrogel was prepared to improve the osteogenic microenvironment of stem cells. The arginine–glycine–aspartate (RGD) peptide promoted the adhesion and proliferation of stem cells, and the degradation of gelatin microspheres (GMs) produced a macroporous structure to enhance further the migration and aggregation of stem cells. Mesoporous silica nanoparticles (MSNs) sustained-release bone-forming peptide-1 (BFP-1) induced osteogenic differentiation, and the sustained release of the QK peptide from the GMs promoted angiogenesis. In vitro experiments have shown that this functionalized hydrogel stimulates the proliferation of hMSCs, encourages larger cell cluster formation, and enhances the osteogenic differentiation efficiency. The released QK facilitates the proliferation and migration of endothelial cells. In vivo experiments have also verified that this system has a better osteogenic effect, and more blood vessels were observed inside the hydrogel, than in other systems. In general, this research has led to the development of a tripeptide macroporous hydrogel that can simultaneously promote osteogenesis and angiogenesis, showing great promise for applications of 3D cultures and stem cell-based tissue engineering.
研究领域:
生物材料
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组织工程
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干细胞生物学
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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
ADVANCED MATERIALS
·
2025
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IF 26.8
Wentao Wang,Zhenyu Li,Siming Zhang,Yue Ma,Lei Yu,Qidong Zhang,Guoqing Pan,Dechun Geng,Chen Zhu,Jiaxiang Bai
The reduced initial stability of orthopedic implants in osteoporotic bone matrices, coupled with excessive M1 macrophage polarization at bone-implant interfaces, disrupt bone–immune homeostasis and vascularization, ultimately leading to implant loosening or failure. Inspired by the marine mussel Mytilus edulis foot protein (Mefp), a pH-responsive multifunctional bone glue (YDC-Gel-Zn) with broad-spectrum adhesion capabilities is developed for osteoporotic bone-implant integration. This pseudo-Mefp bioglue enables dual-interface adhesion via catechol-rich sequences that mediate stable metal-phenolic coordination with metallic implants and hydrogen-bonded/Michael addition-driven interactions with the bone matrix, thereby improving initial implant fixation. Under osteoporotic inflammatory microenvironments, sequential dissociation of borate ester bonds and metal‒phenolic coordination facilitates the controlled release of Zn 2 ⁺ and proangiogenic/osteogenic peptides (YDC). The released Zn 2 ⁺ remodels glutathione metabolism through glutathione S-transferase (GST)-mediated regulation of glutathione (GSH) levels, inhibits JAK1/STAT1/NLRP3 inflammasome activation, and suppresses the release of proinflammatory cytokines from senescent M1 macrophages, recalibrating the osteo-vascular-immune microenvironment. Due to its positive effects on bone regeneration and angiogenesis, the bioinspired bone bioglue demonstrated a 194% increase in fixation strength in osteoporotic rat models, achieving 93% healthy bone-implant stability. Overall, this study provides a clinically translatable strategy for stable implantation under osteoporotic conditions through synergistic mechanical adaptation, bioactivity regulation, and smart environmental responsiveness.
研究领域:
生物医学工程
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生物材料
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组织工程
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骨科
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免疫调节
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再生医学
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生物粘合剂
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纳米医学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Zuyuan Luo,Siqi Zhang,Jijia Pan,Rui Shi,Hao Liu,Yalin Lyu,Xiao Han,Yan Li,Yue Yang,Zhixiu Xu,Yi Sui,En Luo,Yuanyuan Zhang,Shicheng Wei
The efficacy of stem cell-based bone tissue engineering has been hampered by cell death and limited fate control. A smart cell culture system with the capability of sequentially delivering multiple factors in specific growth stages, like the mechanism of the natural extracellular matrix modulating tissue formation, is attractive for enhancing cell activity and controlling cell fate. Here, a bone forming peptide-1 (BFP-1)-laden mesoporous silica nanoparticles ( [email protected] ) incorporated adhesion peptide, containing the arginine-glycine-aspartic acid (RGD) domain, modified alginate hydrogel (RA) system ( [email protected] ) was developed to promote the activity and stimulate osteo-differentiation of human mesenchymal stem cells (hMSCs) in sequence. The survivability and proliferation of hMSCs were enhanced in the adhesion peptide modified hydrogel. Next, BFP-1 released from [email protected] induced hMSCs osteo-differentiation after the proliferation stage. Moreover, BFP-1 near the cells was self-captured by the additional cell-peptide cross-linked networks formed by the ligands (RGD) binding to receptors on the cell surface, leading to long-term sustained osteo-stimulation of hMSCs. The results suggest that independent and sequential stimulation in proliferation and osteo-differentiation stages could synergistically enhance the survivability, expansion, and osteogenesis of hMSCs, as compared to stimulating alone or simultaneously. Overall, this study provided a new and valid strategy for stem cell expansion and osteo-differentiation in 2D or 3D culture systems, possessing potential applications in 3D bio-printing and tissue regeneration .
研究领域:
组织工程
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干细胞生物学
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生物医用材料
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再生医学
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产品关联
DOI
PubMed
高影响因子