CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Yufeng Ai,Jingting Wu,Wenfeng Li,Fancheng Xu,Jianxin Wu,Li Li,Kaiqiang Yang,Chenjiang He,Pengyan Zhu,Xueli Leng,Fang Dai,Li Song
In the aging society, bone defects significantly threaten human health. Therefore, several biomaterials have been developed to promote bone regeneration. However, previous studies have predominantly focused on optimizing the osteoinductive capacity of materials while neglecting vascular regeneration and immune responses elicited by biomaterials. The repair of bone defects is a complex biological process that involves not only bone resorption and formation, but also inflammation, immunity, and vascularization. The present study successfully encapsulated deferoxamine (DFO) into poly (lactic-co-glycolic acid) (PLGA) to form nanospheres for the sustained release of DFO, thereby simulating a hypoxic microenvironment. DFO-PLGA/Bioactive glass (BG)/Bone marrow mesenchymal stem cells (BMSCs) @GelMA (DBB@GelMA) exhibited excellent biocompatibility and osteoinductive properties in vitro. Furthermore, DBB@GelMA continuously releases DFO to promote vascular regeneration, M2 polarization of macrophages, and osteogenic differentiation of BMSCs. The finding from the experiment on SD rat calvarial defect repair further validated its exceptional immunoregulatory, angiogenic, and osteoinductive capabilities. In conclusion, this composite hydrogel offers a novel strategy for regulating the hypoxic microenvironment and holds promise for bone-defect repair.
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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DOI
高影响因子
Nano Materials Science
·
2025
·
IF 17.9
Weikang Zhao,Biemin Sun,Yu Song,Yuan Cao,Yichen Liu,Dandan Zhou,Qiang Zhou,Feng Xie,Wei Huang,Xiaoxiao Li,Yuling Li,Yanqin Xu,Yiyang Wang
Osteochondral defects pose an enormous challenge, and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone. Constructing a scaffold with biological function and biomimetic structure is the key to achieving a high-quality repair effect. Herein, a natural polymer-based bilayer scaffold with a porous architecture similar to that of osteochondral tissue is designed, involving the transforming growth factor-beta3-liposome-loaded upper layer for superficial cartilage regeneration and the nanohydroxyapatite-coated lower layer for subchondral bone rehabilitation. This research is conducted to evaluate the effects of nanoparticle-modified bilayer scaffold to mimic the hierarchical pro-chondrogenic and pro-osteogenic microenvironment for the recruited endogenous bone marrow mesenchymal stem cells. The fabricated composites were evaluated for mechanical, physicochemical, biological properties, in vitro and in vivo tissue regeneration potential. Overall, the current bilayer scaffold could regenerate a cartilage-bone integrated tissue with a seamless interfacial integration and exhibited superior tissue repair outcomes compared to other single layer scaffolds based on morphological, radiological and histological evaluation, verifying that this novel graft could be an effective approach to tissue-engineered analogs of cartilage-subchondral bone and offer new therapeutic opportunities for osteochondral defect-associated diseases.
研究领域:
组织工程学
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再生医学
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生物材料学
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DOI
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
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2026
·Vol. 57
·期 1
·30
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IF 2.2
Xiang Shouyu,Liu Wei,Tang Cheng,Xie Chuhai,Hu Hailan,Zhou Jianhui,Cao Yanming,Ling Long
Bone marrow mesenchymal stem cells (BMSCs) play a significant role in bone defect repair. Currently, the limited survival and function of transplanted BMSCs pose major obstacles to tissue repair mediated by these cells. Therefore, the exploration of BMSCs transplantation activity has become an urgent clinical problem. In this experiment, we constructed lentiviral vectors with overexpression and silencing of miR-19b-3p and utilized a rat fracture model. The effects of BMSCs proliferation were examined using CCK-8, the Annexin V-FITC apoptosis kit and TUNEL assay, the effects of BMSCs osteogenic differentiation were detected using ALP and Alizarin red staining. Furthermore, Western blotting and qRT-PCR were employed to examine the expression of key proteins in the PTEN/Akt/mTOR signaling pathway and autophagy-related proteins. Moreover, the impact of miR-19b-3p on bone microstructure was assessed using Micro CT, HE, Safranin O/Fast Green, as well as Masson staining, and Immunohistochemistry analysis examined PTEN, p62 and Runx2 expression levels on fracture site. By constructing lentiviral vectors with overexpression and silencing of miR-19b-3p, we found that silencing miR-19b-3p significantly promoted the proliferation as well as the osteogenic differentiation of BMSCs under hypoxia. Western blotting and qRT-PCR results showed that silencing miR-19b-3p significantly increased PTEN, LC3, and Beclin1 expression while decreasing p-Akt, p-mTOR, and p62 expression. Furthermore, by constructing the fracture rats and administering hypoxia-treated BMSCs transfected with miR-19b-3p via tail vein injection, we found that silencing miR-19b-3p obviously increased the formation of trabecular and promoted the healing of the fractures. Immunohistochemistry analysis showed that silencing miR-19b-3p upregulated PTEN and Runx2 expression levels and suppressed p62 expression with statistical significance. In summary, these findings suggest that miR-19b-3p may regulate BMSCs’ autophagy and osteogenic differentiation under hypoxia via the PTEN/Akt/mTOR signaling pathway, thereby promoting fracture healing and providing a potential target for the treatment of fractures.
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DOI
PubMed
高影响因子
Biomaterials Advances
·
2024
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IF 5.5
Xingyu Zhu,Huanjin Liu,Chunmei Mei,Fugui Chen,Mengyu Guo,Chenxu Wei,Dan Wang,Meimei Luo,Xiaofang Hu,Yuwei Zhao,Fangyu Hao,Changcan Shi,Weidong Li
Tissue engineering shows promise in repairing extensive bone defects. The promotion of proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by biological scaffolds has a significant impact on bone regeneration outcomes. In this study we used an injectable hydrogel, known as aminated mesoporous silica gel composite hydrogel (MSNs-NH 2 @GelMA), loaded with a natural drug, processed pyritum (PP), to promote healing of bone defects. The mechanical properties of the composite hydrogel were significantly superior to those of the blank hydrogel. In vitro experiments revealed that the composite hydrogel stimulated the osteogenic differentiation of BMSCs, and significantly increased the expression of type I collagen (Col 1), runt-related transcription factor 2 (Runx 2), alkaline phosphatase (ALP), osteocalcin (OCN). In vivo experiments showed that the composite hydrogel promoted the generation of new bones. These findings provide evidence that the composite hydrogel pyritum-loaded holds promise as a biomaterial for bone repair.
研究领域:
组织工程学
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再生医学
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材料科学
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细胞生物学
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DOI
PubMed
高影响因子
Materials Today Bio
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2024
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IF 8.7
Linquan Zhou,Chengcheng Zhang,Tengbin Shi,Dingwei Wu,Huina Chen,Jiaxin Han,Dehui Chen,Jinxin Lin,Wenge Liu
The migration and differentiation of bone marrow mesenchymal stem cells (BMSCs) play crucial roles in bone repair processes. However, conventional scaffolds often lack of effectively inducing and recruiting BMSCs. In our study, we present a novel approach by introducing a 3D-bioprinted scaffold composed of hydrogels, with the addition of laponite to the GelMA solution, aimed at enhancing scaffold performance. Both in vivo and in vitro experiments have confirmed the outstanding biocompatibility of the scaffold. Furthermore, for the first time, Apt19s has been chemically modified onto the surface of the hydrogel scaffold, resulting in a remarkable enhancement in the migration and adhesion of BMSCs. Moreover, the scaffold has demonstrated robust osteogenic differentiation capability in both in vivo and in vitro environments. Additionally, the hydrogel scaffold has shown the ability to induce the polarization of macrophages from M1 to M2, thereby facilitating the osteogenic differentiation of BMSCs via the bone immune pathway. Through RNA-seq analysis, it has been revealed that macrophages regulate the osteogenic differentiation of BMSCs through the AMPK/mTOR signaling pathway. In summary, the functionalized GelMA/Laponite scaffold offers a cost-effective approach for tailored in situ bone regeneration.
研究领域:
组织工程
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生物材料
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再生医学
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骨免疫学
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产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2026
·Vol. 17
·期 1
·312
·
IF 7.8
Shao Qi,Shi Jianhong,Lu Jin,Tian Yuanye
Background Craniofacial bone defects represent significant clinical challenges resulting from diverse etiological factors. Despite advancements in biomaterials science, autologous tissue transplantation remains the gold standard for craniofacial reconstruction due to the limitations of existing materials in replicating the complexity and functionality of native tissues. Objective This study aimed to investigate the efficacy of combining 3D-printed nano-hydroxyapatite (n-HA) scaffolds with concentrated growth factor-enriched cell sheets (CGF-BMSCs-CS) for bone defect repair, exploring their synergistic effects on osteogenesis and tissue regeneration. Methods Bone marrow mesenchymal stem cells (BMSCs) were utilized to fabricate CGF-enriched cell sheets. 3D-printed porous n-HA scaffolds (5 mm diameter, 1 mm thickness) were prepared and wrapped with CGF-BMSCs-CS to form composite scaffolds. Four experimental groups were established: control, n-HA alone, CGF-BMSCs-CS alone, and the composite n-HA/CGF-BMSCs-CS. Osteogenic potential was evaluated through alkaline phosphatase (ALP) activity assays and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis of osteogenesis-related gene expression. Sprague-Dawley rats were randomly assigned to these groups for a cranial defect model. Micro-computed tomography (µCT) was performed at 6 and 12 weeks post-surgery to assess bone regeneration metrics, including bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th). Results Scanning electron microscopy (SEM) confirmed the n-HA scaffold’s uniform porosity and structural integrity. The CGF-BMSCs-CS exhibited optimal thickness and viscosity for tissue engineering applications. The composite group demonstrated significantly elevated ALP activity and upregulated expression of osteogenesis-related genes, indicating enhanced osteogenic capacity. µCT analysis revealed superior bone formation and osseointegration in the composite scaffold group compared to other groups. This was further supported by significantly higher bone mineral density (BMD) values at both time points ( p < 0.05). Histological evaluation via hematoxylin and eosin (H&E) staining showed increased osteocyte activity, neovascularization, and trabecular bone formation in the composite group. Conclusions We innovatively integrated 3D printed n-HA scaffolds with CGF BMSCs CS, which combines mechanical stability with enhanced osteogenic potential for craniofacial bone defect repair, promoting bone healing. This innovative strategy provides promising prospects for advancing bone tissue engineering and regenerative medicine. Graphical
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DOI
高影响因子
ACS Applied Polymer Materials
·
2025
·
IF 4.7
Jing Qu,Wenjing Zhang,Qi Xiao,Zhe Gao,Wei Ma,Jiajia Peng,Mingzhong Li
Bone loss that occurs during trauma, surgeries, or tumor resection often leads to bone defects, which need to be filled with substitutionary materials. Bioactive hydrogels show better prospects for bone regeneration. In this research, the biodegradable silk fibroin (SF) and hydrophilic mercapto sodium hyaluronate (MSH), combined with the MSH-modified nanohydroxyapatite (nHAp-MSH), were jointly used to construct a ternary composite hydrogel SF/MSH/nHAp-MSH with the ability to induce osteogenesis. The surface and interior of the composite hydrogel were composed of numerous regularly arranged and evenly distributed pores, and its porosity varied from 50%–83%. As the secondary structure of the porous gel was mainly composed of a regular β-sheet, it maintained an appropriate hydrophilic swelling property while possessing excellent mechanical properties. After 4 w of degradation, the mass loss of the gel was approximately 40%, and the pores were slightly damaged, which ensured that it matched the bone formation rate and maintained the required spatial structure. In vitro experiments revealed that the composite hydrogel promoted the adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs) and stimulated their osteogenic differentiation by enhancing the expression of alkaline phosphatase (ALP). These findings provide evidence that the SF/MSH/nHAp-MSH composite hydrogel holds promise as a biomaterial for bone repair.
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DOI
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
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2023
·
IF 4.9
Feng Qian,Zongwang Huang,Wenbin Liu,Yanling Liu,Xi He
Segmental bone defects caused by trauma, tumor resection or congenital malformations are often reconstructed with autologous, allogeneic bone grafts or artificial bone materials, of which, about 5% ~ 10% will have delayed healing or even nonunion of fractures. The loss of periosteum and excessive accumulation of ROS in fracture site leads to the aging of osteoblasts and the decline of their proliferation and differentiation, thus affecting the fracture healing process. In this study, we prepared a functional modified artificial periosteum β-TCP/MnO 2 /PCL(β-TMP) by electrospinning with a function of catalyzing decomposition of H 2 O 2 . We examined the surface morphology of β-TMP, the concentration of Ca, P and Mn of β-TMP, as well as the diameter distribution range of nanofibers on β-TMP. Through X-ray diffraction patterns and Fourier transform infrared spectra, β-TMP was characterized and its hydrophilicity was tested. The release of Mn 2+ and Ca 2+ of 0.1 and 0.05% β-TMP in different pH values (7.4 and 5.5) determined by ICP. We also identified that β-TMP could reduce the level of ROS in cells by lowering the level of H 2 O 2 . 0%, 0.05% and 0.1% β-TMP displayed good cell compatibility, cell adhesion and cellular morphology in the condition with or without H 2 O 2 . 0.5% β-TMP showed compromised cell compatibility in normal condition, however, the compromised phenotypes could be partially rescued in the present of H 2 O 2 . Compared with 0%, 0.05% and 0.1% β-TMP displayed higher osteoblastic differentiation with or without H 2 O 2 in BMSCs as well as in MG-63. In sum, β-TMP helped osteogenesis and promoted repair of bone defects.
研究领域:
材料科学
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再生医学
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组织工程
·
骨科
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Guanlu Shen,Xinxin Si,Lei Qiang,Yihao Liu,Zhiyang Yin,Jing Shan,Pengfei Zheng
Growth plate injuries in children and adolescents often lead to bone bridge formation, resulting in limb deformities due to the limited self-repair capacity of the growth plate. The limitations of traditional treatments prompted interest in the role of the extracellular matrix (ECM) and mechanical environment in tissue repair. Recent research showed that 3D hydrogels could mimic ECM to regulate mesenchymal stem cells (MSCs) differentiation, with MSCs sensing matrix viscoelasticity via Piezo1 and responding through the ROCK signaling pathway. This study aimed to develop a 3D biomimetic hydrogel composed of acellular cartilage matrix methacryloyl (ACMMA) and gelatin methacryloyl (GelMA), with adjustable viscoelasticity via blue light crosslinking time. Hydrogels with low (5 s) and high (20s) modulus were fabricated and loaded with bone marrow mesenchymal stem cells (BMSCs). Results demonstrated that the 5 s hydrogel promoted chondrogenic differentiation and inhibited osteogenesis, effectively preventing bone bridge formation and enhancing growth plate repair in vivo . Mechanistic studies confirmed that the 5 s group did not activate the Piezo1-ROCK pathway, supporting its role in chondrogenic differentiation.
研究领域:
生物医学工程
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组织工程
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干细胞研究
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生物材料
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骨科
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
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IF 10
Junjun Yang,Xiaoyuan Gong,Tao Li,Zengzilu Xia,Rui He,Xiongbo Song,Xin Wang,Jiangyi Wu,Jiajia Chen,Fangzheng Wang,Ran Xiong,Yangjing Lin,Guangxing Chen,Liu Yang,Kaiyong Cai
In this study, the regulatory role and mechanisms of tantalum (Ta) particles in the bone tissue microenvironment are explored. Ta particle deposition occurs in both clinical samples and animal tissues following porous Ta implantation. Unlike titanium (Ti) particles promoting M1 macrophage (Mϕ) polarization, Ta particles regulating calcium signaling pathways and promoting M2 Mϕ polarization. Ta-induced M2 Mϕ enhances bone marrow-derived mesenchymal stem cells (BMSCs) proliferation, migration, and osteogenic differentiation through exosomes (Exo) by upregulating miR-378a-3p/miR-221-5p and downregulating miR-155-5p/miR-212-5p. Ta particles suppress the pro-inflammatory and bone resorption effects of Ti particles in vivo and in vitro. In a rat femoral condyle bone defect model, artificial bone loaded with Ta particles promotes endogenous Mϕ polarization toward M2 differentiation at the defect site, accelerating bone repair. In conclusion, Ta particles modulate Mϕ polarization toward M2 and influence BMSCs osteogenic capacity through Exo secreted by M2 Mϕ, providing insights for potential bone repair applications.
研究领域:
生物材料
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免疫学
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骨生物学
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干细胞研究
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再生医学
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DOI
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Wenxin Qi,Naijun Dong,Lingling Wu,Xueqi Zhang,He Li,Hao Wu,Natalie Ward,Jian Yu,He Liu,Jiao Wang,Xiaoyong Deng,Robert Chunhua Zhao
The high occurrence rate and difficulties in symptom control are listed as the major problems of oral mucosal disease by medical professionals. Following the development of oral mucosal lesions, the oral microenvironment changes, immunity declines, and continuous bacterial stimulation causes wound infection. Traditional antibacterial drugs are ineffective for oral mucosal lesions. To overcome this problem, a light-responsive antibacterial hydrogel containing sustained-release BMSCs was inspired by the trauma environment in the oral cavity, which is different from that on the body surface since it mostly remains under dark conditions. In the absence of light, the hydrogel seals the wound to form a barrier, exerts a natural bacteriostatic effect, and prevents invasion by foreign bacteria. Simultaneously, mesenchymal stem cells are presented, and the released growth factors and other substances have excellent anti-inflammatory and angiogenic effects, which result in rapid repair of the damaged site. Under light conditions, after photo-induced shedding of the hydrogel, RuB 2 A exerts an antibacterial effect accompanied by degradation of the hydrogel. Results in a rat oral mucosal repair model demonstrate that DCS-RuB 2 A 2 -BMSCs could rapidly repair the oral mucosa within 4 days. Sequencing data provide ideas for further analysis of the intrinsic molecular mechanisms and signaling pathways. Taken together, our results suggest that this light-responsive antibacterial hydrogel loaded with BMSCs can be used for rapid wound repair and may advance the development of therapeutic strategies for the treatment of clinical oral mucosal defects.
研究领域:
生物医学工程
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组织工程
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口腔医学
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干细胞研究
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产品关联
DOI
PubMed
高影响因子
Small
·
2023
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IF 13.3
Shaowei Pan,Zhaowei Yin,Chen Shi,Haonan Xiu,Guanfu Wu,Yongyuan Heng,Zhangyu Zhu,Jing Zhang,Jianchao Gui,Ziyi Yu,Bin Liang
The study investigated whether both the osteogenic and angiogenic potential of Exos (Exosomes) can be enhanced by overexpression of exosomal miRNA (microRNA) and to confirm whether Exos loaded in HMPs (Hydrogel microparticles) exert long-term effects during new bone formation. BMSCs and Exos are successfully obtained. In vitro and in vivo experiments confirmed that HDAC4 (Histone deacetylase 4) is inhibited by miR-29a overexpression accompanied by the upregulation of RUNX2 (Runt-related transcription factor 2) and VEGF (Vascular Endothelial Growth Factor), thereby enhancing osteogenic and angiogenic capabilities. The HMP@Exo system is synthesized from HB-PEGDA (Hyperbranched Poly Ethylene Glycol Diacrylate)- and SH-HA (Sulfhydryl-Modified Hyaluronic Acid)-containing Exos using a microfluidic technique. The HMP surface is modified with RGD (Arg-Gly-Asp) peptides to enhance cell adhesion. The system demonstrated good injectability, remarkable compatibility, outstanding cell adhesion properties, and slow degradation capacity, and the sustained release of Agomir-29a-Exos (Exosomes derived from Agomir-29a transfected BMSCs) from HMPs enhanced the proliferation and migration of BMSCs and HUVECs (Human Umbilical Vein Endothelial Cells) while promoting osteogenesis and angiogenesis. Overall, the findings demonstrate that the HMP@Exo system can effectively maintain the activity and half-life of Exos, accompanied by overexpression of miR-29a (microRNA-29a). The injectable system provides an innovative approach for accelerating fracture healing by coupling osteogenesis and angiogenesis.
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DOI
PubMed
高影响因子
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