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ACS Nano · 2022 · IF 18.027

Bone ECM-like 3D Printing Scaffold with Liquid Crystalline and Viscoelastic Microenvironment for Bone Regeneration

Kun Liu,Lin Li,Jingsheng Chen,Yizhi Li,Wei Wen,Lu Lu,Lihua Li,Hong Li,Mingxian Liu,Changren Zhou,Binghong Luo

Implanting a 3D printing scaffold is an effective therapeutic strategy for personalized bone repair. As the key factor for the success of bone tissue engineering, the scaffold should provide an appropriate bone regeneration microenvironment and excellent mechanical properties. In fact, the most ideal osteogenic microenvironment is undoubtedly provided by natural bone extracellular matrix (ECM), which exhibits liquid crystalline and viscoelastic characteristics. However, mimicking a bone ECM-like microenvironment in a 3D structure with outstanding mechanical properties is a huge challenge. Herein, we develop a facile approach to fabricate a bionic scaffold perfectly combining bone ECM-like microenvironment and robust mechanical properties. Creatively, 3D printing a poly(l-lactide) (PLLA) scaffold was effectively strengthened via layer-by-layer electrostatic self-assembly of chitin whiskers. More importantly, a kind of chitin whisker/chitosan composite hydrogel with bone ECM-like liquid crystalline state and viscoelasticity was infused into the robust PLLA scaffold to build the bone ECM-like microenvironment in 3D structure, thus highly promoting bone regeneration. Moreover, deferoxamine, an angiogenic factor, was encapsulated in the composite hydrogel and sustainably released, playing a long-term role in angiogenesis and thereby further promoting osteogenesis. This scaffold with bone ECM-like microenvironment and excellent mechanical properties can be considered as an effective implantation for bone repair.

CAS / MDL: 9012-76-4
研究领域: 生物医学工程 · 组织工程 · 材料科学
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MATERIALS TECHNOLOGY · 2024 · IF 2.9

3D-printed endovascular scaffold loaded with miR-199a-5p promotes the functional repair of atherosclerosis

Mengcheng Xu,Maolin Zhao

Among deaths related to cardiovascular disease (CVD), arteriosclerosis accounts for three-quarters of the total. The most common treatment for arteriosclerosis is revascularization through the implantation of endovascular scaffolds. However, most metal scaffolds currently available are non-biodegradable, which can lead to rejection reactions. In this study, we have developed a CMCS-PEI/miR polysaccharide nucleic acid nanodrug loaded with miR-199a-5p for the first time. The CMCS-PEI/miR polysaccharide nucleic acid nanodrug exhibits good blood compatibility, successfully transfects cells, and induces apoptosis of vascular endothelial cells. Additionally, PCL/GO composite scaffolds with excellent mechanical properties and biocompatibility were fabricated using 3D printing technology. This technology allows for the customisation of scaffolds to meet the needs of individual patients. The 3D-printed PCL/GO composite scaffolds loaded with CMCS-PEI/miRNA polysaccharide nucleic acid nanodrug effectively induce apoptosis of vascular endothelial cells, showing great potential in promoting the functional repair of arteriosclerosis and preventing vascular restenosis.

研究领域: 心血管疾病 · 生物材料学 · 分子生物学 · 组织工程
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BMEMat · 2024 · IF 0

Thickening tissue by thinning electrospun scaffolds for skeletal muscle tissue engineering

Shuo Wang,Xinhuan Wang,Minxuan Jia,Wenli Liu,Qi Gu

Electrospun scaffolds with aligned fiber orientation are widely used in tissue engineering, such as muscle, heart, nerve, tendon, and cartilage, due to their ability to guide cell morphology and induce cellular functions. However, the dense fibrous structure of the scaffolds poses a critical obstacle to engineering highly cellular and thick 3D tissues, as it prevents cell infiltration. While many techniques have been developed to increase the pore size of electrospun scaffolds and improve cell infiltration/migration, it often leads to a decrease in direct cell-cell contact, compromising cell differentiation and tissue maturation. This study presents an alternative approach by reducing the thickness of scaffolds to the cellular scale and stacking or rolling the cell-scaffold complex into 3D constructs. We devise a series of novel tools to fabricate, characterize, and manipulate ultra-thin electrospun scaffolds, which demonstrate high reproducibility, resolution, and cellularity. Our study provides a solution to the cell infiltration issue in muscle tissue engineering and is highly versatile, and can be applied to various fields that require structures with high-resolution gradients in a layered pattern or complex spatial distribution in a rolled pattern.

研究领域: 生物医学工程 · 组织工程 · 材料科学 · 细胞生物学
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MATERIALS & DESIGN · 2019 · IF 5.77

3D printing of biomimetic multi-layered GelMA/nHA scaffold for osteochondral defect repair

Jingyi Liu,Liang Li,Hairui Suo,Mengling Yan,Jun Yin,Jianzhong Fu

Currently, osteochondral defects frequently cause limited motion and impaired function of the joint, leading to serious healthcare problems, and it is still very challenging to realize the simultaneous regeneration of subchondral bone with cartilage. In the current study, we designed a tri-layered scaffold and fabricated it using the extrusion-based multi-nozzle 3D printing technology. The bioinks used for 3D printing included a 15% methacrylated gelatin (GelMA) hydrogel for cartilage on top layer, a combination of 20% GelMA and 3% nanohydroxyapatite (nHA) (20/3% GelMA/nHA) hydrogel for interfacial layer, and a 30/3% GelMA/nHA hydrogel for subchondral bone at bottom layer. The water absorption capacity, biodegradation, and mechanical properties of hydrogels and scaffolds were characterized, and in vitro assay with bone marrow mesenchymal stem cells (BMSCs) was performed to indicate the biocompatibility of scaffolds. Based on the results of in vivo repair of rabbit osteochondral defect, the neo-tissues in defects integrated better with the surrounding tissues, the joint surface of the defects was smoother, and more cartilage-specific extracellular matrix and collagen type II were observed using the tri-layered scaffolds. This study not only provides a potential manufacturing method for multi-layered scaffolds, but also is helpful for understanding the regeneration mechanism of cartilage-subchondral bone.

研究领域: 组织工程 · 再生医学 · 生物医用材料 · 骨科手术
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MATERIALS & DESIGN · 2025 · IF 7.9

Sustained oxygen release Organic/Inorganic composite scaffold Delivers BMSCs to promote spinal cord injury repair

Jun Hu,Xiqiang Zhong,Jiacheng Wang,Minghai Dai,Liangle Liu,Xiaofu Pan

The clinical repair of spinal cord injury (SCI) has long been constrained by the twin challenges of a persistent hypoxic microenvironment at the injury site and the low survival rate of transplanted cells. This study innovatively constructs a three-dimensional (3D) oxygen-releasing scaffold Poly(lactic-co-glycolic acid (PLGA)-Calcium Peroxide (CPO)/Gelatin Methacryloyl (PLGA-CPO/GelMA) featuring a core–shell structure achieved via emulsification-photocrosslinking technology. PLGA-CPO microspheres provide sustained oxygen release for over 14 days, while the GelMA hydrogel establishes a biomimetic microenvironment.   In vitro   experiments confirmed that under hypoxic conditions, the hydrogel composite scaffold maintained the proliferative activity of the bone marrow mesenchymal stem cells during 3D co-culture. Furthermore, when co-cultured with neurons in a 2D system simulating the   in vivo   SCI environment, the scaffold significantly promoted neuronal survival and proliferation. In a T9 complete transection SCI rat model, the scaffold transplantation group exhibited significantly improved Basso, Beattie, Bresnahan locomotor scores compared to control groups. Histological analysis revealed increased axonal regeneration, reduced glial scarring, and high survival rates of transplanted mesenchymal stem cells at the implantation site in the scaffold-treated group. Mechanistic studies demonstrated that the composite scaffold exerted a triple synergistic effect, encompassing promotion of angiogenesis and neural regeneration, alongside suppression of apoptotic responses.   The developed Organic/Inorganic Composite scaffold sustainably ameliorates the injury microenvironment and synergistically enhances stem cell-mediated repair efficacy, providing a promising tissue engineering solution with significant potential for clinical translation in spinal cord injury.

研究领域: 生物医学工程 · 组织工程 · 神经再生 · 干细胞治疗 · 生物材料学 · 转化医学 · 创伤修复
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JOURNAL OF BIOMATERIALS APPLICATIONS · 2019 · IF 2.442

Preparation and optimization of a gelatin-based biomimetic three-layered vascular scaffold

Qingxi Hu,Chuang Wu,Haiguang Zhang

Electrospinning is promising approach for producing biomimetic vascular scaffolds. In particular, gelatin-based electrospun scaffolds offer excellent biocompatibility. However, gelatin-based vascular scaffolds are difficult to remove from the collector after electrospinning and cross-linking agents such as glutaraldehyde, which is commonly used to improve the strength of water-soluble electrospun gelatin, are highly toxic. Herein, we present a novel electrospinning method for preparing three-layered vascular scaffolds. First, Tween 80 was added to 2,2,2-trifluoroethanol as the polymer electrospinning solution and the gelatin electrospinning solution was mixed with polylactic acid and polycaprolactone, respectively. The three-layered vascular scaffold was fabricated by electrospinning an inner layer of gelatin, a middle layer of polyester, and another outer layer of gelatin. Finally, the electrospun scaffolds were cross-linked with microbial transglutaminase and vacuum dried. Biomechanical properties of the scaffold were determined by tensile testing. Furthermore, the structure and biocompatibility of the scaffolds were assessed by hydrophilicity tests, scanning electron microscopy, and cell seeding experiments. Our results suggest the proposed electrospinning method is suitable for preparing biomimetic vascular scaffolds for cardiovascular tissue engineering applications. Moreover, this paper provides a useful reference for the preparation and optimization of vascular scaffolds.

CAS / MDL: 111-30-8
研究领域: 组织工程学 · 生物材料科学 · 生物医学工程
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Materials Today Advances · 2025 · IF 8

Vascularized and neuralized bone regeneration using injectable double-network cross-linked scaffolds with fully biomimetic organic and biomineralized microenvironments

Runquan Zheng,Xuesong Yan,Baoxing Tian,Suode Li,Jiawei Li,Zhaozhe Yao,Yongxian Zhang,Xianhu Yue

text. At present, reliable and effective therapeutic strategies for physiological bone regeneration are lacking. In this study, a novel injectable double-network cross-linked scaffold with fully biomimetic organic and biomineralized microenvironments for vascularized and neuralized bone regeneration was designed. Our design involved a dual-network collagen organic framework scaffold (COL1/3) with a ratio based on the natural bone composition. Subsequently, the optimal concentration (4 %) of COL1/3 scaffold for osteogenesis was determined on the basis of its efficiency in subcutaneous bone regeneration. In addition, 2 % multiple native bone inorganic salts were integrated into the COL1/3 scaffold to create a biomimetic biomineralized microenvironment. Consequently, double-network cross-linked scaffolds with a fully biomimetic organic and biomineralized microenvironment were successfully fabricated. Furthermore, in vitro studies showed that the scaffold exhibited good biocompatibility and promoted the secretion of bone-specific proteins while upregulating the expression level of osteogenic genes involved in bone microtissues formation. Finally, in vivo studies on rabbit skull defect repair indicated that the current repair strategy could enhance vascularized and neuralized bone regeneration.

CAS / MDL: 6066-82-6
研究领域: 生物材料学 · 组织工程 · 再生医学 · 骨科学 · 生物医学工程 · 分子生物学 · 神经生物学
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International Journal of Bioprinting · 2017 ·Vol. 3 ·期 1 ·009 · IF 0

Influence of electrohydrodynamic jetting parameters on the morphology of PCL scaffolds

Hang Liu,Sanjairaj Vijayavenkataraman,Dandan Wang,Linzhi Jing,Jie Sun,Kai He

One of the important constituents in tissue engineering is scaffold, which provides structural support and suitable microenvironment for the cell attachment, growth and proliferation. To fabricate micro/nano structures for soft tissue repair and three-dimensional (3D) cell culture, the key is to improve fibre-based scaffold fabrication. Electrohydrodynamic (EHD) jetting is capable of producing and orientating submicron fibres for 3D scaffold fabrication. In this work, an EHD-jetting system was developed to explore the relationship between vital processing parameters and fibre characteristics. In this study, polycaprolactone (PCL) solution prepared by dissolving PCL pellets in acetic acid was used to fabricate the scaffolds. The influence of voltage, motorized stage speed, solution feed rate, and solution concentration on fibre characteristics and scaffold pattern were studied. Morphology of the EHD-jetted PCL fibres and scaffolds were analysed using optical microscope images and scanning electron microscope (SEM) images. Multi-layer scaffolds with the varied coiled pattern were fabricated and analysed. Cell attachment and proliferation have to be investigated in the future by further cell culture studies on these multi-layer coiled scaffolds.

研究领域: 生物材料 · 组织工程 · 高分子科学 · 再生医学 · 生物制造
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Advanced Materials Interfaces · 2023 · IF 5.4

Preparation of ROS-Responsive Exosome Coating of Nitinol Material for Making the Neurointerventional Stent

Lin Duan,Yanyan He,Haigang Wu,Tianxiao Li,Jia Liang,Rufeng Jia,Dehua Guo,Taoyuan Lu,Chi Ma,Wenbo Liu,Yingkun He

Nitinol (NiTi) alloy is an ideal material for preparing neurointerventional stents due to its excellent mechanical properties and biocompatibility. However, NiTi stents without surface-specific functionalization cause a high rate of stent thrombosis and in-stent restenosis after implantation. In ischemic stroke, exosomes have a role in regulating nervous system development, regeneration, vascular remodeling, and neuroinflammation. In this work, the effect of exosome coating on the biocompatibility of NiTi alloy is evaluated. NiTi alloy is successively immersed in relevant solution (sodium alginate, 3-aminophenylboronic acid, distearoylphosphatidylethanolamine, and exosomes) to form ROS-responsive exosome coated surfaces. In vitro experiments (platelets, endothelial cells, smooth muscle cells, and macrophages) and in vivo subcutaneous implantation experiments are performed to test coatings for biocompatibility. The results show that the modified NiTi alloy surface has high hydrophilicity, which has the functions of inhibiting platelet aggregation, promoting endothelialization, inhibiting smooth muscle cell migration, anti-inflammatory, and good tissue biocompatibility. This study develops exosome neurointerventional stent coating as a bioactive drug via reactive oxygen species accumulation in lesions, thus targeting drug release, inhibiting intimal hyperplasia, and reducing inflammation and thrombosis.

CAS / MDL: 6066-82-6 9005-38-3
研究领域: 材料科学 · 生物医学工程 · 神经科学 · 生物材料 · 组织工程
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BIOMATERIALS · 2024 · IF 12.8

Construction of PVA/OHA-Gs@PTMC/PHA double-layer nanofiber flexible scaffold with antibacterial function for tension free rectal in-situ reconstruction

Bingxu Zhang,Xujian Li,Chuan Jiang,Chuanguang Wang,Haifeng Que,Cheng Zheng,Zhixiao Ji,Xudong Tao,Hongtao Xu,Changcan Shi

The effective prevention and treatment of anastomotic leakage after intestinal anastomosis for colorectal diseases is still a major clinical challenge. In order to assist intestinal anastomosis healing and avoid anastomotic leakage caused by high tension, low blood supply or infection, we designed a double-layer nanofiber intestinal anastomosis scaffold, which was composed of electrospun PTMC/PHA nanofibers as the main layer, and electrospun PVA/OHA-Gs nanofibers with antibacterial properties as the antibacterial surface layer. This double-layer scaffold has good toughness, its maximum tensile force value could reach 8 N, elongation could reach 400 %, and it has hydrophilic properties, and its contact angle was about 60°. On the basis of reducing anastomotic tension and isolating intestinal contents, this double-layer nanofiber anastomotic scaffold not only played an antibacterial effect in the short term after surgery to reduce inflammatory response, but also had the characteristics of multiple three-dimensional network structure like extracellular matrix which could promote tissue healing. The PVA/OHA-Gs@PTMC/PHA scaffold was implanted into a rabbit model simulating mechanical intestinal obstruction, and the results showed that the nanofibers of the scaffold could be degraded in vivo while maintaining a certain stability, that is, the overall structure of the PVA/OHA-Gs@PTMC/PHA scaffold would not shrink and deform due to degradation in a certain period of time. Therefore, the treatment with this scaffold showed better healing at the anastomotic site. Compared to the direct anastomosis group and pure PTMC scaffold group, the double-layer scaffold group promoted a faster return to normal anastomotic strength within 7 days. This PVA/OHA-Gs@PTMC/PHA double-layer nanofiber flexible scaffold appears to be a promising therapeutic strategy to prevent anastomotic leakage after intestinal anastomosis.

研究领域: 生物医学工程 · 组织工程 · 外科手术研究
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Polymers · 2022 ·Vol. 14 ·期 7 ·1400 · IF 4.967

Fabrication and Characterization of Gelatin/Polyvinyl Alcohol Composite Scaffold

Mengwen Sun,Yajuan Wang,Lihui Yao,Ya Li,Yunxuan Weng,Dan Qiu

In this study, porous scaffold materials based on polyvinyl alcohol (PVA) and gelatin (Gel) were successfully fabricated and characterized. The mechanism of the reaction, morphology, and crystallinity were investigated by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). In addition, thermogravimetric analysis (TGA) was performed together with differential scanning calorimetry (DSC) for examining the thermostability and phase transformation of the scaffolds. Degradation and swelling studies of PVA/Gel composite scaffold materials were performed in phosphate-buffered saline. Finally, the mechanical performances had been determined. According to the results, the polymer matrix that was formed by the combination of PVA and gelatin had better thermal stability. The synthesized composite scaffold was amorphous in nature. The addition of gelatin did not affect the fishbone-like microstructure of PVA, which ensures the excellent mechanical properties of the PVA scaffold. The denaturation temperature and elastic modulus of the PVA scaffold were improved by the gelatin addition, but the physical and chemical properties of the PVA scaffold were weakened when the gelatin content exceeded 10%. In addition, the PVA-10G sample has suitable degradability. Therefore, the PVA/Gel composite scaffold might potentially be applied in the field of tissue engineering that demands high strength.Keywords:polyvinyl alcohol;gelatin;porous scaffold

CAS / MDL: 9002-89-5
研究领域: 生物材料学 · 组织工程学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Electrospun gelatin-based biomimetic scaffold with spatially aligned and three-layer architectures for vascular tissue engineering

Shanzhu Guo,Yue Jiang,Jingjing Jiao,Yan Shi,Tao Zhu,Long Li

The spatial cellular alignment and multi-layer structure are vitally important for the physiological functions of natural blood vessels. However, the two features are difficult to be constructed in one scaffold simultaneously, especially in the small-diameter vascular scaffold. Here we report a general strategy to construct a gelatin-based biomimetic three-layer vascular scaffold with spatial alignment features mimicking the natural structure of blood vessels. By using a sequential electrospinning strategy combined with folding and rolling manipulation, a three-layer vascular scaffold with inner and middle layers spatially perpendicular to each other was obtained. The special features of this scaffold could fully mimic the natural multi-layer structures of blood vessels and also possess great potential for spatial arrangement guidance of corresponding cells in blood vessels.

CAS / MDL: 989-38-8 47165-04-8
研究领域: 组织工程 · 生物材料 · 生物医学工程
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