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Nano Life · 2021 · IF 0

4D Printing of Self-Folding Hydrogel Tubes for Potential Tissue Engineering Applications

Yu-Dong Zhao,Jia-Hui Lai,Min Wang

In recent years, 4D printing has gained increasing attention in the tissue engineering field since this advanced manufacturing platform can create stimulus-responsive structures, which can change their shapes, functions, and/or properties when appropriate external stimulus/stimuli is/are applied. A number of hydrogels with swellable/shrinkable abilities have been explored for 4D printing to fabricate different shape-morphing structures for tissue engineering. Among them, gelatin methacryloyl (GelMA) has been 4D printed, which can self-fold into microtubular structures. Currently, the self-folding ability of 4D printed GelMA hydrogels is mainly based on the different cross-linking degrees (which control and govern the swelling degrees) across the thickness of hydrogels. However, this strategy alone can only form self-folding GelMA tubes with diameters at the micrometer level and cannot create self-folding GelMA tubes with diameters at the millimeter level, which is mainly due to the insufficient internal force generated in 4D printed GelMA hydrogels when they are exposed to water. To overcome this limitation, this study has investigated a new strategy to fabricate self-folding GelMA tubes with large diameters at the millimeter level for tissue engineering applications. The new strategy introduced a cross-linking degree gradient across the GelMA plane in addition to its thickness by printing a second layer of strips on the first 4D printed GelMA film. In the aqueous environment, under the current fabrication condition, such bilayer GelMA hydrogels could self-fold into tubes of larger diameters up to 6 mm. The in vitro release behavior of heparin incorporated into the 4D printed GelMA was also studied. It was shown that heparin release could be controlled by the GelMA concentration and heparin content in 4D printed GelMA. The 4D printed GelMA hydrogels with the improved self-folding ability and controlled release of a drug are promising for targeted tissue engineering applications.

研究领域: 生物医学工程 · 材料科学 · 组织工程
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MOLECULES · 2019 ·Vol. 24 ·期 8 ·1633 · IF 3.06

Microfluidics-Based Fabrication of Cell-Laden Hydrogel Microfibers for Potential Applications in Tissue Engineering

Gen Wang,Luanluan Jia,Fengxuan Han,Jiayuan Wang,Li Yu,Yingkang Yu,Gareth Turnbull,Mingyu Guo,Wenmiao Shu,Bin Li

Fibrous hydrogel scaffolds have recently attracted increasing attention for tissue engineering applications. While a number of approaches have been proposed for fabricating microfibers, it remains difficult for current methods to produce materials that meet the essential requirements of being simple, flexible and bio-friendly. It is especially challenging to prepare cell-laden microfibers which have different structures to meet the needs of various applications using a simple device. In this study, we developed a facile two-flow microfluidic system, through which cell-laden hydrogel microfibers with various structures could be easily prepared in one step. Aiming to meet different tissue engineering needs, several types of microfibers with different structures, including single-layer, double-layer and hollow microfibers, have been prepared using an alginate-methacrylated gelatin composite hydrogel by merely changing the inner and outer fluids. Cell-laden single-layer microfibers were obtained by subsequently seeding mouse embryonic osteoblast precursor cells (MC3T3-E1) cells on the surface of the as-prepared microfibers. Cell-laden double-layer and hollow microfibers were prepared by directly encapsulating MC3T3-E1 cells or human umbilical vein endothelial cells (HUVECs) in the cores of microfibers upon their fabrication. Prominent proliferation of cells happened in all cell-laden single-layer, double-layer and hollow microfibers, implying potential applications for them in tissue engineering.Keywords:microfluidics;microfibers;cell-laden;tissue engineering

研究领域: 生物材料 · 组织工程 · 生物医学工程
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Journal of Materials Research and Technology-JMR&T · 2024 · IF 6.2

Magnetic scaffold constructing by micro-injection for bone tissue engineering under static magnetic field

Zhengyi Xu,Yujie Zhang,Lang Zheng,He Cai,Xiangjun Yang,Yiyuan Xue,Qianbing Wan,Junyu Chen,Yijun Li

The utilization of static magnetic fields in conjunction with tissue engineering scaffolds has demonstrated significant potential in the restoration of bone defects. However, previous techniques used for fabricating magnetic tissue engineering scaffolds have shown certain shortcomings that require further investigation. In this study, a series of scaffolds made from a combination of polylactic acid (PLA), polycaprolactone (PCL), and iron tetraoxide (Fe 3 O 4 ) nanoparticles were designed and prepared using the microinjection molding technique. The composite scaffolds, which were doped with nanoparticles and fabricated through microinjection, exhibited exceptional physicochemical properties and biocompatibility. Additionally, the PLA/PCL/Fe 3 O 4 scaffolds were found to promote the proliferation and adhesion of bone marrow cells (BMSCs) under relatively low magnetic fields (25–30 mT). These findings suggest that PLA/PCL/Fe 3 O 4 scaffolds hold great potential for use in bone tissue engineering applications.

CAS / MDL: 1317-61-9
研究领域: 生物医学工程 · 材料科学 · 组织工程
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ACS Applied Nano Materials · 2021 · IF 5.097

Polyaniline Protrusions on MoS2 Nanosheets for PVDF Scaffolds with Improved Electrical Stimulation

Fangwei Qi,Xiuwen Gao,Shuping Peng,Wenjing Yang,Guowen Qian,Sheng Yang,Cijun Shuai

Piezoelectric polyvinylidene fluoride (PVDF) provided an opportunity for non-invasive in situ electrical stimulation of cell behavior, yet its electroactive β phase was difficult to obtain due to its instability in the molten state. Herein, polyaniline (PANI) protrusions were in situ oxidation-polymerized on molybdenum disulfide (MoS2) nanosheets (PANI-MoS2). Then, PANI-MoS2 was introduced into laser additive-manufactured PVDF scaffolds. On the one hand, PANI protrusions produced steric hindrance between adjacent MoS2 nanosheets and inhibited the stacking and aggregating of MoS2. On the other hand, PANI-MoS2 could serve as a platform to achieve interfacial polarization locking. Specifically, Mo–S dipoles in MoS2 and π electron clouds over the N atom in PANI locked −CH2 dipoles in PVDF through electrostatic and hydrogen bond interactions, respectively, which forced −CH2 to align perpendicularly to the basal plane of MoS2 and bialy to one side of the PVDF main chain, thereby forming a full-reverse planar zigzag configuration of the polarized β phase and maintaining its stable existence. The results demonstrated that the β phase of the scaffolds was significantly increased from 43 to 90%, which resulted in an enhanced electrical output performance. The improved electrical output greatly promoted osteoblast-like cell proliferation and differentiation. Furthermore, owing to the pulling-out effect of MoS2 and improved interfacial stress transfer between MoS2 and the polymer matrix, the mechanical properties of scaffolds were also enhanced. These findings suggested that the piezoelectric scaffolds had great potential in bone tissue engineering.

研究领域: 材料科学 · 生物医学工程 · 组织工程
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Gels · 2023 ·Vol. 9 ·期 5 ·373 · IF 4.6

Chitosan Hydrogel as Tissue Engineering Scaffolds for Vascular Regeneration Applications

Qiulin Wang,Xiaoyu Wang,Yakai Feng

Chitosan hydrogels have a wide range of applications in tissue engineering scaffolds, mainly due to the advantages of their chemical and physical properties. This review focuses on the application of chitosan hydrogels in tissue engineering scaffolds for vascular regeneration. We have mainly introduced these following aspects: advantages and progress of chitosan hydrogels in vascular regeneration hydrogels and the modification of chitosan hydrogels to improve the application in vascular regeneration. Finally, this paper discusses the prospects of chitosan hydrogels for vascular regeneration.Keywords:chitosan;hydrogel;tissue engineering;vascular regeneration;angiogenesis

CAS / MDL: 9012-76-4
研究领域: 生物材料 · 组织工程 · 再生医学
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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

A Janus Mg2+ and H2 Pump Conduit for Enhanced Peripheral Nerve Regeneration

Wei Yu,Xinru Zhang,Muge Gu,Yihui Zhang,Xiangqi Zhang,Jiayu Wang,Genjiang Zheng,Wei-En Yuan

Peripheral nerve injuries, often caused by trauma and tumor resection, severely impair motor and sensory functions. While autologous nerve grafting remains the gold standard, its efficiency is hindered by limited donor tissue availability, donor site morbidity, and neuropathic pain. Tissue-engineered nerve grafts, emerging as promising alternatives, still face challenges due to the lack of essential biochemical and biophysical cues for comprehensive nerve regeneration. This study introduces a Janus Mg 2+ /H 2 pump conduit, constructed with a MgH 2 @PLGA middle layer, polycaprolactone (PCL) outer layers, and a polydopamine-coated PCL (PCL@PDA) inner layer. The PCL provides structural support, while the MgH 2 @PLGA layer continuously releases Mg 2+ and H 2 as biochemical cues, driven by an acidic microenvironment and the MgH 2 -water reaction. PDA modification of the inner layer, serving as biophysical cues, further increases cell adhesion. Mg 2+ released from the conduit mitigates oxidative stress in Schwann cells and increases their expression of neurotrophic factors, while the H 2 attenuates inflammation, aiding nerve regeneration. In a rat sciatic nerve defect model, the conduit shows enhanced functional, electrophysiological, and histological recovery. These findings highlight the potential of Janus Mg 2+ /H 2 pump conduit as a promising approach for peripheral nerve defect repair by offering a conducive microenvironment.

CAS / MDL: 7786-30-3 24980-41-4
研究领域: 神经科学 · 生物材料学 · 再生医学
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Science China-Chemistry · 2015 ·Vol. 58 ·期 12 ·1866-1874 · IF 1.695

Dual-peptide-modified alginate hydrogels for the promotion of angiogenesis

Yu Yanyan,Guo Lei,Wang Wei,Wu Jina,Yuan Zhi

The ability to supply suitable blood vessel system is a major challenge for artificial thick tissue engineering. Angiogenesis is a key point during the process of microvascular formation. Many bioactive molecules such as extra cellular matrix (ECM) proteins and adhesion peptides derived from the ECM are applied to promote angiogenesis. In this work, two adhesion peptides, YIGSR and REDV, were selected to modify sodium alginate (ALG) to obtain YIGSR- and REDV-alginate conjugates (ALG-YIGSR, and ALG-REDV, respectively). We mixed the two peptide-conjugates together in a series of concentration ratios to prepare bioactive surfaces for in vitro studies and hydrogel scaffolds for in vivo studies. In vitro studies showed that surfaces modified with 1.09 pmol/mm 2 peptide had the best affinity to human umbilical vein endothelial cells (HUVECs) than that with high or low concentrations of peptides. In addition, surfaces modified with dual peptides could significantly promote HUVECs proliferation, where ALG-YIGSR:ALG-REDV at a mole ratio of 5:1 exhibited the best enhancement ability. Furthermore, the in vivo angiogenesis results demonstrated that hydrogel scaffolds composed of mixed ALG-YIGSR and ALG-REDV at the 5:1 ratio had angiogenic induction potential by stimulating new blood vessel formation, and showed higher blood vessel density than scaffolds composed of a single peptide. These results demonstrated that a mixed combination of peptide alginate conjugates could be a potential scaffold to stimulate and induce angiogenesis in tissue engineering applications.

研究领域: 生物材料学 · 细胞生物学 · 医学工程
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BIOMATERIALS · 2015 · IF 8.557

Injectable glycopolypeptide hydrogels as biomimetic scaffolds for cartilage tissue engineering

Kaixuan Ren,Chaoliang He,Chunsheng Xiao,Gao Li,Xuesi Chen

Glycopolypeptides are an emerging class of bioinspired polymers that mimic naturally occurring glycopeptides or glycoproteins , and therefore are expected to exhibit great potential for biomedical applications . In this study, a glycopolypeptide was synthesized by conjugation of poly(γ-propargyl- l -glutamate) (PPLG) with azido-modified mannose and 3-(4-hydroxyphenyl) propanamide (HPPA), via click chemistry. Injectable hydrogels based on the glycopolypeptide were developed through enzymatic crosslinking reaction in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H 2 O 2 ). The physicochemical properties of the hydrogels, such as gelation time, storage modulus , swelling and degradation time , could be controlled by varying the concentrations of HRP and H 2 O 2 . The glycopolypetide copolymer as well as the extracts of the glycopolypetide hydrogels displayed good cytocompatibility in vitro . After subcutaneous injection into rats, the glycopolypeptide hydrogels were rapidly formed in situ , and exhibited acceptable biocompatibility accompanying the degradation of the hydrogels in vivo . The rabbit chondrocytes inside the glycopolypeptide hydrogels showed spherical morphology with high viability during the incubation period of 3 weeks in vitro , and exhibited a higher proliferation rate than within the hydrogel counterparts of PPLG grafted with 2-(2-(2-methoxyethoxy)ethoxy)ethane (MEO 3 ) and HPPA. Biochemical analysis demonstrated that the production of glycosaminoglycans (GAG) and type II collagen were significantly enhanced after incubation for 2 and 3 weeks in vitro . Moreover, the chondrocyte-containing glycopolypeptide hydrogels in subcutaneous model of nude mice maintained chondrocyte phenotype and produced the cartilaginous specific matrix. These results indicated that the biomimetic glycopolypeptide-based hydrogels hold potential as three-dimensional scaffolds for cartilage tissue engineering .

研究领域: 生物材料学 · 再生医学 · 组织工程
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2016 · IF 3.902

Degradation pattern of porous CaCO3 and hydroxyapatite microspheres in vitro and in vivo for potential application in bone tissue engineering

Qiwei Zhong,Wenhua Li,Xiuping Su,Geng Li,Ying Zhou,Subhas C. Kundu,Juming Yao,Yurong Cai

Despite superior clinical handling, excellent biocompatibility, biodegradation property of calcium phosphate needs to be improved to coincide with the rate of new bone formation. In this study, spherical CaCO 3 are fabricated in the presence of the silk sericin and then transformed into porous hydroxyapatite (HAP) microspheres via hydrothermal method. The degradation behavior of obtained CaCO 3 , HAP and their mixture is first investigated in vitro . The result demonstrates that the weight loss of HAP microspheres are almost 24.3% after immersing in pH 7.40 Tris-HCl buffer solution for 12 weeks, which is far slower than that of spherical CaCO 3 (97.5%). The degradation speed of the mixtures depends on the proportion of CaCO 3 and HAP. The mixture with higher content of CaCO 3 possesses a quicker degradation speed. The obtained CaCO 3 and HAP microspheres are injected into subcutaneous tissue of ICR mice with the assistance of sodium alginate. The result in vivo also shows an obvious difference of degradation speed between the obtained CaCO 3 and HAP microspheres, implying it is feasible to modulate the degradation property of the mixture through changing the proportion of CaCO 3 and HAP The good cytocompatibility of the two kinds of microspheres is proved and a mild inflammation response is observed only at early stage of implantation. The job offers a simple method to modify the degradation properties of biomaterial for potential use in bone tissue engineering.

研究领域: 材料科学 · 生物材料 · 组织工程
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MOLECULES · 2019 ·Vol. 24 ·期 9 ·1669 · IF 3.06

Fabrication and Application of Novel Porous Scaffold in Situ-Loaded Graphene Oxide and Osteogenic Peptide by Cryogenic 3D Printing for Repairing Critical-Sized Bone Defect

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

CAS / MDL: 75-09-2
研究领域: 生物医学工程 · 材料科学 · 组织工程
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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY · 2016 ·Vol. 16 ·期 5 ·4718-4726 · IF 1.338

Applying Electrospun Gelatin/Poly(lactic acid-co-glycolic acid) Bilayered Nanofibers to Fabrication of Meniscal Tissue Engineering Scaffold

Li Peng,Zhang Weiguo,Yu Hongquan,Zheng Lianjie,Yang Liang,Liu Gang,Sheng Chenchen,Gui Haoran,Ni Shuo,Li Pengsheng,Shi Feng

The menisci are fibrocartilaginous tissues composed primarily of an interlacing network of collagen fibers with nanoscale diameter. Electrospinning is a suitable process of producing nanoscale fibers that mimic collagen fibers. In this study, a bilayered scaffold (group B), which consists of a gelatin nanofiber mesh and a PLGA nanofiber mesh, has been fabricated through an electrospinning method. At the same time, we electrospun pure PLGA fibrous mesh (group A) and gelatin/PLGA composite fibrous mesh (group C) as control groups. In order to compare all scaffold morphologies, the scaffolds were imaged by SEM and some parameters were measured and analyzed as following: Diameters of fibrils are from the smallest of less than average 0.14 μm for group C to the biggest of nearly average 0.38 μm for group B. The scaffolds pore diameters are from average 4.9 μm for group A to average 11.2 μm for group B. Porosity rates show that the group B has the highest porosity rate at about 91%. The scaffolds’ properties were compared and analyzed, including hydrophilicity property (water contact angle) and mechanical properties (tensile strength). The results of water contact angle showed the group B is the most hydrophil among the groups. The results of tensile strength showed the tensile strength of group C is the weakest among the groups. All the results showed significant differences between the groups. Finally, in vitro, the meniscal cells derived from New Zealand white rabbits menisci were seeded in the scaffolds. We observed the cells proliferation behavior in the scaffolds. All above demonstrates that a bi-layered gelatin/PLGA scaffold reveals not only concurrent effects of mechanics and cytocompatibility in a fibrous context, but also a promising scaffold for future meniscal repair strategies.

研究领域: 生物材料学 · 组织工程学
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ACS Applied Bio Materials · 2018 · IF 0

Spider-Inspired Multicomponent 3D Printing Technique for Next-Generation Complex Biofabrication

You Zhou,Shenglong Liao,Xinglei Tao,Xiao-Qi Xu,Quan Hong,Di Wu,Yapei Wang

The shortage of tissue resources is currently a serious challenge that limits the clinical therapy to patients with tissue loss or end-stage organ failure. The booming development of 3D printing offers unprecedented hope for tissue engineering since it can construct cells and biomaterials into a 3D tissue-mimicking object with precise control over size and shape. However, it is still challenging to fabricate artificial living tissues or organs due to the extreme complexity of biological tissues. Herein, we propose a new concept of spider-inspired 3D printing technique (SI-3DP) for continuous multicomponent 3D printing based on in situ gelation at a multibarrel printing nozzle. The printing process allows for rapid construction of 3D architectures composed of different inks in the desired position. To present the potential in biomedical applications, the SI-DIP also prints vessel-like hollow hydrogel microfibers and cell-laden hollow fibers, indicating good biocompatibility of this technique. The newly developed SI-3DP technique is envisioned to promote the development of next-generation complex biofabrication.

研究领域: 生物医学工程 · 组织工程 · 再生医学
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