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MATERIALS & DESIGN · 2022 · IF 9.417

Preparation and characterization of bovine serum albumin nanoparticles modified by Poly-l-lysine functionalized graphene oxide for BMP-2 delivery

Fan Liu,Lei Xue,Li Xu,Jun Liu,Chungang Xie,Cen Chen,Yi Liu

The development of bioactive carrier with controlled delivery of Bone morphogenetic protein (BMP-2) is an important part in bone regeneration. Our study fabricated novel modified nanomaterials based on poly-l-lysine functionalized graphene oxide (GO-PLL) and explore its potential applications for BMP-2 delivery. GO-PLL was used to modify BMP-2 encapsulated bovine serum albumin (BSA) nanoparticles (GO-PLL/BMP-2) by self-assembling technology. The physiochemical and biological properties of GO-PLL modified BSA nanoparticles were investigated in vitro . Additionally, rabbit calvarial bone defects were created to investigate bone formation ability in the presence of GO-PLL/BMP-2 loaded alginate/gelatin scaffolds. The results suggested BSA particles were spatially interacted with GO-PLL complexes by strong electrostatic attraction. When compared with BMP-2 encapsulated BSA nanoparticles, a pronounced decrease in BMP-2 gentle release was observed in the presence of GO-PLL/BMP-2 nanoparticles, and extended to over 14-day release periods. More importantly, GO-PLL/BMP-2 nanoparticles significantly enhanced alkaline phosphatase activity (ALP) and matrix mineralization, and exhibited favorable bone formation ability when loaded into alginate/gelatin scaffolds. These results demonstrated that PLL functionalized GO complexes are considered as appropriate delivery system for BSA modification, and have great potential for BMP-2 delivery in bone regeneration.

研究领域: 纳米技术 · 生物医学工程 · 骨组织工程 · 药物递送系统
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International Journal of Nanomedicine · 2018 · IF 4.37

Thermally induced self-agglomeration 3D scaffolds with BMP-2-loaded core–shell fibers for enhanced osteogenic differentiation of rat adipose-derived stem cells

Shuying Hu,Hanbang Chen,Xuefeng Zhou,Gang Chen,Ke Hu,Yi Cheng,Lili Wang,Feimin Zhang

Introduction Scaffold structure plays a vital role in cell behaviors. Compared with two-dimensional structure, 3D scaffolds can mimic natural extracellular matrix (ECM) and promote cell–cell and cell–matrix interactions. The combination of osteoconductive scaffolds and osteoinductive growth factors is considered to have synergistic effects on bone regeneration. Materials and methods In this study, core–shell poly(lactide-co-glycolide) (PLGA)/polycaprolactone (PCL)–BMP-2 (PP–B) fibrous scaffolds were prepared through coaxial electrospinning. Next, we fabricated 3D scaffolds based on PP–B fibers with thermally induced self-agglomeration (TISA) method and compared with conventional PLGA/PCL scaffolds in terms of scaffold morphology and BMP-2 release behaviors. Then, rat adipose-derived stem cells (rADSCs) were seeded on the scaffolds, and the effects on cell proliferation, cell morphology, and osteogenic differentiation of rADSCs were detected. Results The results demonstrated that 3D scaffold incorporated with BMP-2 significantly increased proliferation and osteogenic differentiation of rADSCs, followed by PP–B group. Conclusion Our findings indicate that scaffolds with 3D structure and osteoinductive growth factors have great potential in bone tissue engineering.

CAS / MDL: 75-89-8
研究领域: 生物医学工程 · 组织工程 · 干细胞研究
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Advanced Healthcare Materials · 2023 · IF 10

Hydroxyapatite-Coated Small Intestinal Submucosa Membranes Enhanced Periodontal Tissue Regeneration through Immunomodulation and Osteogenesis via BMP-2/Smad Signaling Pathway

Guoping Cheng,Shujuan Guo,Maoxue Li,Shimeng Xiao,Bo Jiang,Yi Ding

Periodontitis, a chronic infection causing periodontal tissue loss, may be effectively addressed with in situ tissue engineering. Small intestinal submucosa (SIS) offers exceptional biocompatibility and biodegradability but lacks sufficient osteoconductive and osteoinductive properties. This study develops and characterizes SIS coated with hydroxyapatite (SIS-HA) and gelatin methacrylate hydroxyapatite (SIS-Gel-HA) using biomineralization and chemical crosslinking. The impact on periodontal tissue regeneration is assessed by evaluating macrophage immune response and osteogenic differentiation potential of periodontal ligament stem cells (PDLSCs) in vitro and rat periodontal defects in vivo. The jejunum segment, with the highest collagen type I content, is optimal for SIS preparation. SIS retains collagen fiber structure and bioactive factors. Calcium content is 2.21% in SIS-HA and 2.45% in SIS-Gel-HA, with no significant differences in hydrophilicity, physicochemical properties, protein composition, or biocompatibility among SIS, SIS-HA, SIS-Gel, and SIS-Gel-HA. SIS is found to upregulate M2 marker expression, both SIS-HA and SIS-Gel-HA enhance the osteogenic differentiation of PDLSCs through the BMP-2/Smad signaling pathway, and SIS-HA demonstrates superior in vitro osteogenic activity. In vivo, SIS-HA and SIS-Gel-HA yield denser, more mature bones with the highest BMP-2 and Smad expression. SIS-HA and SIS-Gel-HA demonstrate enhanced immunity–osteogenesis coupling, representing a promising periodontal tissue regeneration approach.

CAS / MDL: 7647-01-0
研究领域: 口腔科学 · 组织工程 · 再生医学 · 免疫学 · 细胞生物学 · 材料科学
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BIOMATERIALS · 2016 · IF 8.387

Sequential and sustained release of SDF-1 and BMP-2 from silk fibroin-nanohydroxyapatite scaffold for the enhancement of bone regeneration

Xiaofeng Shen,Yanxia Zhang,Yong Gu,Yun Xu,Yong Liu,Bin Li,Liang Chen

In this study, a cell-free bone tissue engineering system based on a silk fibroin (SF)/nano-hydroxyapatite (nHAp) scaffold was developed, in which two bioactive molecules , stromal cell derived factor-1 (SDF-1) and bone morphogenetic protein-2 (BMP-2), were embedded and released in a sequential and controlled manner to facilitate cell recruitment and bone formation, respectively. BMP-2 was initially loaded into SF microspheres , and these BMP-2 containing microspheres were subsequently encapsulated into the SF/nHAp scaffolds, which were successively functionalized with SDF-1 via physical adsorption. The results indicated rapid initial release of SDF-1 during the first few days, followed by slow and sustained release of BMP-2 for as long as three weeks. The composite scaffold significantly promoted the recruitment of bone marrow mesenchymal stem cells (BMSCs) and osteogenic differentiation of them in vitro . Further, the in vivo studies using D-Luciferin-labeled BMSCs indicated that implantation of this composite scaffold markedly promoted the recruitment of BMSCs to the implanted sites. Enhanced bone regeneration was identified at 12 weeks' post-implantation. Taken together, our findings suggested that the sequential and sustained release of SDF-1 and BMP-2 from the SF/nHAp scaffolds resulted in a synergistic effect on bone regeneration. Such a composite system , therefore, shows promising potential for cell-free bone tissue engineering applications .

研究领域: 生物医学工程 · 组织工程 · 再生医学
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Bioactive Materials · 2025 · IF 20.3

An axolotl limb regeneration-inspired strategy to enhance alveolar bone regeneration

Rongpu Liu,Guifang Wang,Li Ma,Guangzheng Yang,Sihan Lin,Ningjia Sun,Jiajia Wang,Huijing Ma,Xinquan Jiang,Wenjie Zhang

Guided bone regeneration (GBR) is widely applied in implant dentistry, employing barrier membranes to create an osteogenic space by preventing gingival tissue ingrowth. However, this method does not enhance the osteogenic capacity of osteoblasts, limiting sufficient bone volume in larger defects. Inspired by axolotl limb regeneration, abundant soft tissue-derived stem cells mobilized to the defect may facilitate comprehensive osteogenesis within a BMP-2-enriched environment. We developed a biomimetic channel system (BCS) to promote alveolar bone regeneration, using channel structures to activate gingival-derived stem cells under a BMP-2-enriched biological barrier. In a cell-tracing mouse model, Prrx1 + stem cells demonstrated a critical role in BMP-2-induced subcutaneous osteogenesis. Sequencing and histological analyses revealed that channel structures significantly enhance soft tissue cell proliferation and migration. Attributable to the biological barrier, BCS applications markedly improved bone formation in beagle mandibular defects. These results suggest a novel osteoinductive strategy for alveolar bone regeneration that functions without a traditional barrier membrane.

CAS / MDL: 9000-70-8
研究领域: 口腔医学 · 再生生物学 · 组织工程
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Biomaterials Research · 2024 · IF 8.1

Immunoregulation in Skull Defect Repair with a Smart Hydrogel Loaded with Mesoporous Bioactive Glasses

Shiguo Yuan,Boyuan Zheng,Kai Zheng,Zhiheng Lai,Zihang Chen,Jing Zhao,Shaoping Li,Xiaofei Zheng,Peng Wu,Huajun Wang

Skull defect repair is a complex and critical medical challenge, and there is an urgent need to develop multifunctional tissue engineering scaffolds for skull regeneration. The success of bone tissue engineering depends on the construction of scaffolds that can regulate the immune microenvironment of bone regeneration and mimic the liquid crystal and viscoelastic properties of natural bone extracellular matrix. Hence, a smart hydrogel (PEGDA5/AM15/CLC-BMP-4@MBG) with good biocompatibility and the ability to modulate the wound immune microenvironment has been developed for the repair of skull defects. The hydrogel consists of chitin liquid crystal hydrogel (PEGDA5/AM15/CLC) and mesoporous bioactive glasses (MBGs) loaded with bone morphogenetic protein-4 (BMP-4). The liquid crystal hydrogel not only offers the necessary biological support and mechanical properties but also maintains the stability of the liquid crystal state, facilitating adhesion and regeneration of surrounding bone tissue. In addition, BMP-4@MBG intelligently regulates the release rate of BMP-4 in response to changes in wound microenvironment, thus effectively promoting the transformation of macrophages from M1 to M2 macrophages. At the same time, Ca2+ and Si4+ released by MBG degradation and BMP-4 synergically promote bone repair process. The PEGDA5/AM15/CLC-BMP-4@MBG hydrogel shows excellent immunomodulatory and osteogenic properties of bone microenvironment and is a promising scaffold material for bone tissue engineering.

CAS / MDL: 1398-61-4
研究领域: 生物医学工程 · 组织工程 · 材料科学 · 免疫学
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2025 · IF 5.4

NIR-responsive CaCO3@ BMP-2/PDA nanocomposite for multifunctional therapy in periodontitis

Xue Chen,Jiemei Bi,Haoyang Zhang,Mengtong Yuan,Jianjiao Wang,Narisu Hu

Periodontitis is a chronic inflammatory disease caused by dental plaque biofilm. To prevent disease progression and achieve successful periodontal tissue repair, it is necessary to simultaneously address the need for antibacterial, anti-inflammatory, and osteogenic effects within deep lesions. This study proposes a novel approach using a NIR light-responsive nanocomposite for enhanced ossification and combating bacterial biofilm infections in periodontitis. The nanocomposite incorporates polydopamine-coated calcium carbonate nanoparticles and BMP-2, which exhibits excellent photothermal conversion efficiency for bacterial eradication. Additionally, polydopamine also serves as an efficient ROS scavenger, thereby reducing the inflammatory response associated with periodontal disease. The core CaCO 3 interacts with BMP-2 to promote bone regeneration. This strategy demonstrates a synergistic effect by integrating PTT, ROS therapy, and osteogenic therapy in treating biofilm-induced periodontitis. Moreover, the CaCO 3 @BMP-2/PDA NPs reduced the protein expression levels of pro-inflammatory cytokines TNF-α and IL-1β and mitigated LPS-induced inflammation. This combination not only achieved critical protective effects but also fostered the promotion of osteoblast differentiation.

研究领域: 生物医学工程 · 口腔医学 · 材料科学
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iScience · 2022 · IF 6.107

Construction of tissue-engineered nucleus pulposus by stimulation with periodic mechanical stress and BMP-2

Yang Liu,Gong-ming Gao,Kai-yuan Yang,Lu-ming Nong

Summary Intervertebral disc (IVD) degeneration, which is common among elderly individuals, mainly manifests as low back pain and is caused by structural deterioration of the nucleus pulposus (NP) due to physiological mechanical stress. NP mesenchymal stem cells (NPMSCs) around the IVD endplate have multidirectional differentiation potential and can be used for tissue repair. To define favorable conditions for NPMSC proliferation and differentiation into chondroid cells for NP repair, the present study simulated periodic mechanical stress (PMS) of the NP under physiological conditions using MSC chondrogenic differentiation medium and recombinant human BMP-2 (rhBMP-2). rhBMP-2 effectively promoted NPMSC proliferation and differentiation. To clarify the mechanism of action of rhBMP-2, integrin alpha 1 (ITG A1) and BMP-2 were inhibited. PMS regulated the BMP-2/Smad1/RUNX2 pathway through ITG A1 and promoted NPMSC proliferation and differentiation. During tissue-engineered NP construction, PMS can effectively reduce osteogenic differentiation and promote extracellular matrix protein synthesis to enhance structural NP recovery.

研究领域: 骨科 · 组织工程 · 干细胞研究 · 力学生物学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2016 · IF 1.733

In vitro evaluation of electrospun silk fibroin/nano-hydroxyapatite/BMP-2 scaffolds for bone regeneration

Bingjie Niu,Bin Li,Yong Gu,Xiaofeng Shen,Yong Liu,Liang Chen

Bone tissue engineering by using osteoinductive scaffolds seeded with stem cells to promote bone extracellular matrix (ECM) production and remodeling has evolved into a promising approach for bone repair and regeneration. In order to mimic the ECM of bone tissue structurally and compositionally, nanofibrous silk fibroin (SF) scaffolds containing hydroxyapatite (HAP) nanoparticles and bone morphogenetic protein 2 (BMP-2) were fabricated in this study using electrospinning technique. The microstructure, mechanical property, biocompatibility, and osteogenic characteristics were examined. It was found that the HAP nanoparticles were successfully incorporated in the SF nanofibers (diameter, 200–500 nm). The mechanical properties of SF/HAP/BMP-2 composite scaffolds increased with HAP content when it was less than 20 wt%, after which the mechanical properties dropped as HAP content increased. Cell culture tests using bone marrow mesenchymal stem cells (BMSCs) showed that the scaffolds had good biocompatibility and promoted the osteogenic differentiation of BMSCs. Therefore, the electrospun SF/HAP/BMP-2 scaffolds may serve as a promising biomaterial for bone tissue engineering.

研究领域: 组织工程 · 材料科学 · 生物材料 · 再生医学
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BIOMATERIALS · 2019 · IF 10.273

Multicellularity-interweaved bone regeneration of BMP-2-loaded scaffold with orchestrated kinetics of resorption and osteogenesis

Haoyi Niu,Yifan Ma,Guangyu Wu,Bing Duan,Ying Wang,Yuan Yuan,Changsheng Liu

Synchronization of material resorption and new bone formation is vital to achieve harmonious bone regeneration in the treatment of large bone defects. To exposit the resorption/osteogenesis properties in the guided bone repairing, rhBMP-2-loaded trimodal macro/micro/nano-porous bioactive glass scaffolds (TMS-rhBMP-2) were set as substrate model. We penetratingly investigated the particular function of hierarchical structure and incorporated rhBMP-2 in the resorption/osteogenesis, and dissected the cellular interplay throughout the regenerative procedure. The results suggested that rhBMP-2 significantly facilitated osteoclastogenesis-mediated scaffold degradation and strikingly up-regulated mesenchymal stem cells (MSCs)-involved osteogenesis in vitro. Further gene microarray and related proteins expression indicated that in the presence of rhBMP-2, MSCs rather than differentiated MSCs could exert synergistic effects on osteoclastogenesis , osteoclasts maturation and resorptive function; meanwhile, rhBMP-2-induced MSCs osteogenesis was also strengthened by the osteoclasts. In vivo micro-CT, X-ray, kinetic and histological analyses qualitatively and quantitively demonstrated the optimized coupling of bioresorption/osteogenesis and the most rapid regeneration in TMS-rhBMP-2. Consequently, with rhBMP-2 acted as ignitor and MSCs/osteoclasts interaction as booster, a harmonious bone regeneration was obtained. Besides, long-term magnetic resonance imaging (MRI) in virtue of Gd 3+ suggested that the degradation products mainly distributed in liver and spleen, verifying the accumulation/discharge profiles and safety application of TMS-rhBMP-2 system in vivo. This study will not merely provide guidance for the design of clinical bone repairing materials, but shed substantial light on the multicell-mediated tissue regeneration .

CAS / MDL: 13450-84-5
研究领域: 生物材料 · 组织工程 · 再生医学 · 细胞生物学 · 生物医学工程
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INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE · 2019 ·Vol. 43 ·期 5 ·2103-2117 · IF 2.928

Loss of Fam20c causes defects in the acinar and duct structure of salivary glands in mice

Nan Miao,Yuanbo Zhan,Yingying Xu,Haoze Yuan,Chunlin Qin,Feng Lin,Xiaohua Xie,Sen Mu,Mengtong Yuan,Haibin Mu,Shouli Guo,Ying Li,Bin Zhang

Family with sequence similarity 20‑member C (FAM20C), a recently characterized Golgi kinase, performs numerous biological functions by phosphorylating more than 100 secreted proteins. However, the role of FAM20C in the salivary glands remains undefined. The present study demonstrated that FAM20C is mainly located in the cytoplasm of duct epithelial cells in the salivary glands. Fam20cf/f; Mmtv‑Cre mice were created in which Fam20c was inactivated in the salivary gland cells and observed that the number of ducts and the ductal cross‑sectional area increased significantly, while the number of acinar cells was reduced. The granular convoluted tubules (GCTs) exhibited an accumulation of aberrant secretory granules, along with a reduced expression and altered distribution patterns of β nerve growth factor, α‑amylase and bone morphogenetic protein (BMP) 4. This abnormality suggested that the GCT cells were immature and exhibited defects in developmental and secretory functions. In accordance with the morphological alterations and the reduced number of acinar cells, FAM20C deficiency in the salivary glands significantly decreased the salivary flow rate. The Na+, Cl– and K+ concentrations in the saliva were all significantly increased due to dysfunction of the ducts. Furthermore, Fam20c deficiency significantly increased BMP2 and BMP7 expression, decreased BMP4 expression, and attenuated the canonical and noncanonical BMP signaling pathways in the salivary glands. Collectively, the results of the present study demonstrate that FAM20C is a key regulator of acinar and duct structure and duct maturation and provide a novel avenue for investigating novel therapeutic targets for oral diseases including xerostomia.

CAS / MDL: 54-71-7 92-13-7
研究领域: 分子生物学 · 发育生物学 · 口腔疾病
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2015 · IF 4.152

Synergistic effect of HA and BMP-2 mimicking peptide on the bioactivity of HA/PMMA bone cement

Zhenzhen Liu,Yong Tang,Ting Kang,Minyu Rao,Kejia Li,Qin Wang,Changyun Quan,Chao Zhang,Qing Jiang,Huiyong Shen

HA and bone morphogenetic protein-2 (BMP-2) possess superior osteoinductive and osteoconductive activities in the repair of bone defects. In this study, a BMP-2 mimicking oligopeptide (serine–serine–valine–proline–threonine, SSVPT) was introduced to the surface of nano-sized HA as the reinforcement phase of a poly(methyl methacrylate) (PMMA) cement, and the synergistic action of HA and oligopeptide on the bioactivity of HA/PMMA bone cement was investigated. Incorporated with 3-trimethoxysilyl propyl methacrylate (MPS)-modified HA, the compressive strength, flexural strength, and flexural modulus of HA/PMMA complied with the international standardization organization 5833 standard. Adherence measurement demonstrated that the introduction of HA and SSVPT could promote the adhesion and proliferation of human fetal osteoblast (hFOB) on the surface of HA/PMMA cement. The increased alkaline phosphatase (ALP) activity indicated that HA/PMMA could promote osteogenic differentiation of hFOB. All of the results illuminated that the HA/PMMA cement could be used as a bioactive material for regeneration and reconstruction of load-bearing bone.

研究领域: 材料科学 · 骨科医学
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