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Current advances for bone regeneration based on tissue engineering strategies

Rui Shi, Yuelong Huang, Chi Ma, Chengai Wu, Wei Tian

《医学前沿（英文）》 2019年第13卷第2期页码 160-188 doi: 10.1007/s11684-018-0629-9

摘要： Bone tissue engineering (BTE) is a rapidly developing strategy for repairing critical-sized bone defects to address the unmet need for bone augmentation and skeletal repair. Effective therapies for bone regeneration primarily require the coordinated combination of innovative scaffolds, seed cells, and biological factors. However, current techniques in bone tissue engineering have not yet reached valid translation into clinical applications because of several limitations, such as weaker osteogenic differentiation, inadequate vascularization of scaffolds, and inefficient growth factor delivery. Therefore, further standardized protocols and innovative measures are required to overcome these shortcomings and facilitate the clinical application of these techniques to enhance bone regeneration. Given the deficiency of comprehensive studies in the development in BTE, our review systematically introduces the new types of biomimetic and bifunctional scaffolds. We describe the cell sources, biology of seed cells, growth factors, vascular development, and the interactions of relevant molecules. Furthermore, we discuss the challenges and perspectives that may propel the direction of future clinical delivery in bone regeneration.

关键词： bone tissue engineering stem cell bone scaffold growth factor bone regeneration

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Bone regeneration by stem cell and tissue engineering in oral and maxillofacial region

Zhiyuan Zhang

《医学前沿（英文）》 2011年第5卷第4期页码 401-413 doi: 10.1007/s11684-011-0161-7

摘要： Clinical imperatives for the reconstruction of jaw bone defects or resorbed alveolar ridge require new therapies or procedures instead of autologous/allogeneic bone grafts. Regenerative medicine, based on stem cell science and tissue engineering technology, is considered as an ideal alternative strategy for bone regeneration. In this paper, we review the current choices of cell source and strategies on directing the osteogenic differentiation of stem cells. The preclinical animal models for bone regeneration and the key translational points to clinical success in oral and maxillofacial region are also discussed. We propose comprehensive strategies based on stem cell and tissue engineering researches, allowing for clinical application in oral and maxillofacial region.

关键词： bone regeneration animal models translational strategies oral and maxillofacial region

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Hybrid polymer biomaterials for bone tissue regeneration

Bo Lei, Baolin Guo, Kunal J. Rambhia, Peter X. Ma

《医学前沿（英文）》 2019年第13卷第2期页码 189-201 doi: 10.1007/s11684-018-0664-6

摘要： Native tissues possess unparalleled physiochemical and biological functions, which can be attributed to their hybrid polymer composition and intrinsic bioactivity. However, there are also various concerns or limitations over the use of natural materials derived from animals or cadavers, including the potential immunogenicity, pathogen transmission, batch to batch consistence and mismatch in properties for various applications. Therefore, there is an increasing interest in developing degradable hybrid polymer biomaterials with controlled properties for highly efficient biomedical applications. There have been efforts to mimic the extracellular protein structure such as nanofibrous and composite scaffolds, to functionalize scaffold surface for improved cellular interaction, to incorporate controlled biomolecule release capacity to impart biological signaling, and to vary physical properties of scaffolds to regulate cellular behavior. In this review, we highlight the design and synthesis of degradable hybrid polymer biomaterials and focus on recent developments in osteoconductive, elastomeric, photoluminescent and electroactive hybrid polymers. The review further exemplifies their applications for bone tissue regeneration.

关键词： hybrid polymer bone regeneration tissue engineering biomaterials

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Tissue engineering of cartilage, tendon and bone

null

《医学前沿（英文）》 2011年第5卷第1期页码 61-69 doi: 10.1007/s11684-011-0122-1

摘要：

Tissue engineering aims to produce a functional tissue replacement to repair defects. Tissue reconstruction is an essential step toward the clinical application of engineered tissues. Significant progress has recently been achieved in this field. In our laboratory, we focus on construction of cartilage, tendon and bone. The purpose of this review was to summarize the advances in the engineering of these three tissues, particularly focusing on tissue regeneration and defect repair in our laboratory. In cartilage engineering, articular cartilage was reconstructed and defects were repaired in animal models. More sophisticated tissues, such as cartilage in the ear and trachea, were reconstructed both in vitro and in vivo with specific shapes and sizes. Engineered tendon was generated in vitro and in vivo in many animal models with tenocytes or dermal fibroblasts in combination with appropriate mechanical loading. Cranial and limb bone defects were also successfully regenerated and repaired in large animals. Based on sophisticated animal studies, several clinical trials of engineered bone have been launched with promising preliminary results, displaying the high potential for clinical application.

关键词： Tissue engineering cartilage bone tendon recent advances

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Primary cilia in hard tissue development and diseases

《医学前沿（英文）》 2021年第15卷第5期页码 657-678 doi: 10.1007/s11684-021-0829-6

摘要： Bone and teeth are hard tissues. Hard tissue diseases have a serious effect on human survival and quality of life. Primary cilia are protrusions on the surfaces of cells. As antennas, they are distributed on the membrane surfaces of almost all mammalian cell types and participate in the development of organs and the maintenance of homeostasis. Mutations in cilium-related genes result in a variety of developmental and even lethal diseases. Patients with multiple ciliary gene mutations present overt changes in the skeletal system, suggesting that primary cilia are involved in hard tissue development and reconstruction. Furthermore, primary cilia act as sensors of external stimuli and regulate bone homeostasis. Specifically, substances are trafficked through primary cilia by intraflagellar transport, which affects key signaling pathways during hard tissue development. In this review, we summarize the roles of primary cilia in long bone development and remodeling from two perspectives: primary cilia signaling and sensory mechanisms. In addition, the cilium-related diseases of hard tissue and the manifestations of mutant cilia in the skeleton and teeth are described. We believe that all the findings will help with the intervention and treatment of related hard tissue genetic diseases.

关键词： primary cilia bone mechanical sensing hard tissue cilium-related bone disease tooth

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Effect of incorporating Elaeagnus angustifolia extract in PCL-PEG-PCL nanofibers for bone tissue engineering

Vahideh R. Hokmabad, Soodabeh Davaran, Marziyeh Aghazadeh, Effat Alizadeh, Roya Salehi, Ali Ramazani

《化学科学与工程前沿（英文）》 2019年第13卷第1期页码 108-119 doi: 10.1007/s11705-018-1742-7

摘要：

Plants have been used for medicinal purposes for thousands of years but they are still finding new uses in modern times. For example, Elaeagnus angustifolia (EA) is a medicinal herb with antinociceptive, anti-inflammatory, antibacterial and antioxidant properties and it is widely used in the treatment of rheumatoid arthritis and osteoarthritis. EA extract was loaded onto poly(ϵ-caprolactone)-poly(ethylene glycol)-poly(ϵ-caprolactone) (PCL-PEG-PCL/EA) nanofibers and their potential applications for bone tissue engineering were studied. The morphology and chemical properties of the fibers were evaluated using Fourier transform infrared spectroscopy, field emission scanning electron microscopy, contact angle measurements and mechanical tests. All the samples had bead-free morphologies with average diameters ranging from 100 to 200 nm. The response of human cells to the PCL-PEG-PCL/EA nanofibers was evaluated using human dental pulp stem cells (hDPSCs). The hDPSCs had better adhesion and proliferation capacity on the EA loaded nanofibers than on the pristine PCL-PEG-PCL nanofibers. An alizarin red S assay and the alkaline phosphatase activity confirmed that the nanofibrous scaffolds induced osteoblastic performance in the hDPSCs. The quantitative real time polymerase chain reaction results confirmed that the EA loaded nanofibrous scaffolds had significantly upregulated gene expression correlating to osteogenic differentiation. These results suggest that PCL-PEG-PCL/EA nanofibers might have potential applications for bone tissue engineering.

关键词： Elaeagnus angustifolia scaffold electrospinning human dental pulp stem cell tissue engineering

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Progress of three-dimensional macroporous bioactive glass for bone regeneration

Lijun JI, Yunfeng SI, Ailing LI, Wenjun WANG, Dong QIU, Aiping ZHU

《化学科学与工程前沿（英文）》 2012年第6卷第4期页码 470-483 doi: 10.1007/s11705-012-1217-1

摘要： Bioactive glasses (BGs) are ideal materials for macroporous scaffolds due to their excellent osteoconductive, osteoinductive, biocompatible and biodegradable properties, and their high bone bonding rates. Macroporous scaffolds made from BGs are in high demand for bone regeneration because they can stimulate vascularized bone ingrowth and they enhance bonding between scaffolds and surrounding tissues. Engineering BG/biopolymers (BP) composites or hybrids may be a good way to prepare macroporous scaffolds with excellent properties. This paper summarizes the progress in the past few years in preparing three-dimensional macroporous BG and BG/BP scaffolds for bone regeneration. Since the brittleness of BGs is a major problem in developing macroporous scaffolds and this limits their use in load bearing applications, the mechanical properties of macroporous scaffolds are particularly emphasized in this review.

关键词： bioactive glass biopolymer bone regeneration macroporous scaffolds tissue engineering

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The stem cell and tissue engineering research in Chinese ophthalmology

GE Jian, LIU Jingbo

《医学前沿（英文）》 2007年第1卷第1期页码 6-10 doi: 10.1007/s11684-007-0002-x

摘要： Much has been considerably developed recently in the ophthalmic research of stem cell (SC) and tissue engineering (TE). They have become closer to the clinical practice, standardized and observable. Leading edge research of SC and TE on the ocular surface reconstruction, neuroregeneration and protection, and natural animal model has become increasingly available. However, challenges remain on the way, especially on the aspects of function reconstruction and specific differentiation. This paper reviews the new developments in this area with an intention of identifying research priorities for the future.

关键词： available observable neuroregeneration protection function reconstruction

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Progress and perspectives of neural tissue engineering

null

《医学前沿（英文）》 2015年第9卷第4期页码 401-411 doi: 10.1007/s11684-015-0415-x

摘要：

Traumatic injuries to the nervous system lead to a common clinical problem with a quite high incidence and affect the patient’s quality of life. Based on a major challenge not yet addressed by current therapeutic interventions for these diseases, a novel promising field of neural tissue engineering has emerged, grown, and attracted increasing interest. This review provides a brief summary of the recent progress in the field, especially in combination with the research experience of the author’s group. Several important aspects related to tissue engineered nerves, including the theory on their construction, translation into the clinic, improvements in fabrication technologies, and the formation of a regenerative environment, are delineated and discussed. Furthermore, potential research directions for the future development of neural tissue engineering are suggested.

关键词： nerve injury tissue engineering nerve grafts

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Nano-hydroxyapatite formation via co-precipitation with chitosan-g-poly(

Yang YU, Hong ZHANG, Hong SUN, Dandan XING, Fanglian YAO

《化学科学与工程前沿（英文）》 2013年第7卷第4期页码 388-400 doi: 10.1007/s11705-013-1355-0

摘要： With the excellent biocompatibility and osteoconductivity, nano-hydroxyapatite (nHA) has shown significant prospect in the biomedical applications. Controlling the size, crystallinity and surface properties of nHA crystals is a critical challenge in the design of HA based biomaterials. With the graft copolymer of chitosan and poly( -isopropylacrylamide) in coil and globule states as a template respectively, a novel composite from chitosan-g-poly( -isopropylacrylamide) and nano-hydroxyapatite (CS-g-PNIPAM/nHA) was prepared via co-precipitation. Zeta potential analysis, thermogravimetric analysis and X-ray diffraction were used to identify the formation mechanism of the CS-g-PNIPAM/nHA composite and its morphology was observed by transmission electron microscopy. The results suggested that the physical aggregation states of the template polymer could induce or control the size, crystallinity and morphology of HA crystals in the CS-g-PNIPAM/nHA composite. The CS-g-PNIPAM/nHA composite was then introduced to chitosan-gelatin (CS-Gel) polyelectronic complex and the cytocompatibility of the resulting CS-Gel/composite hybrid film was evaluated. This hybrid film was proved to be favorable for the proliferation of MC 3T3-E1 cells. Therefore, the CS-g-PNIPAM/nHA composite is a potential biomaterial in bone tissue engineering.

关键词： chitosan poly(N-isopropylacrylamide) hydroxyapatite coil globule bone tissue engineering

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Microorganism-derived biological macromolecules for tissue engineering

《医学前沿（英文）》 2022年第16卷第3期页码 358-377 doi: 10.1007/s11684-021-0903-0

摘要： According to literature, certain microorganism productions mediate biological effects. However, their beneficial characteristics remain unclear. Nowadays, scientists concentrate on obtaining natural materials from live creatures as new sources to produce innovative smart biomaterials for increasing tissue reconstruction in tissue engineering and regenerative medicine. The present review aims to introduce microorganism-derived biological macromolecules, such as pullulan, alginate, dextran, curdlan, and hyaluronic acid, and their available sources for tissue engineering. Growing evidence indicates that these materials can be used as biological material in scaffolds to enhance regeneration in damaged tissues and contribute to cosmetic and dermatological applications. These natural-based materials are attractive in pharmaceutical, regenerative medicine, and biomedical applications. This study provides a detailed overview of natural-based biomaterials, their chemical and physical properties, and new directions for future research and therapeutic applications.

关键词： biological macromolecules regenerative medicine tissue engineering exopolysaccharide carbohydrate

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Fabrication of scaffolds in tissue engineering: A review

Peng ZHAO, Haibing GU, Haoyang MI, Chengchen RAO, Jianzhong FU, Lih-sheng TURNG

《机械工程前沿（英文）》 2018年第13卷第1期页码 107-119 doi: 10.1007/s11465-018-0496-8

摘要：

Tissue engineering (TE) is an integrated discipline that involves engineering and natural science in the development of biological materials to replace, repair, and improve the function of diseased or missing tissues. Traditional medical and surgical treatments have been reported to have side effects on patients caused by organ necrosis and tissue loss. However, engineered tissues and organs provide a new way to cure specific diseases. Scaffold fabrication is an important step in the TE process. This paper summarizes and reviews the widely used scaffold fabrication methods, including conventional methods, electrospinning, three-dimensional printing, and a combination of molding techniques. Furthermore, the differences among the properties of tissues, such as pore size and distribution, porosity, structure, and mechanical properties, are elucidated and critically reviewed. Some studies that combine two or more methods are also reviewed. Finally, this paper provides some guidance and suggestions for the future of scaffold fabrication.

关键词： tissue engineering scaffolds electrospinning 3D printing molding techniques conventional methods

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Visualization of vascular ultrastructure during osteogenesis by tissue engineering technique

ZHANG Kaigang, ZENG Bingfang, ZHANG Changqing

《医学前沿（英文）》 2007年第1卷第2期页码 181-184 doi: 10.1007/s11684-007-0034-2

摘要： The aim of this paper was to observe and visualize the changes in osteoblasts by electron microscopy during osteogenesis using tissue engineering technique. We also studied the feasibility of improving tissue vascularization of th

关键词： feasibility engineering osteogenesis vascularization microscopy

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Current progress on scaffolds of tissue engineering heart valves

DONG Nianguo, SHI Jiawei, CHEN Si, HONG Hao, HU Ping

《医学前沿（英文）》 2008年第2卷第3期页码 229-234 doi: 10.1007/s11684-008-0043-9

摘要： Tissue engineering heart valves (TEHV) may be the most promising valve substitute, but the study has been relatively stagnant in the recent five years due to the special position, function and mechanical property of heart valves. It is one of the key factors to select an ideal scaffold material in the construction of TEHV. And this article will briefly review the current research and progress on the scaffolds of TEHV, especially based on Chinese works.

关键词： function scaffold promising research engineering

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Cryo-copolymerization preparation of dextran-hyaluronate based supermacroporous cryogel scaffolds for tissueengineering applications

Dongjiao ZHOU, Shaochuan SHEN, Junxian YUN, Kejian YAO, Dong-Qiang LIN

《化学科学与工程前沿（英文）》 2012年第6卷第3期页码 339-347 doi: 10.1007/s11705-012-1209-1

摘要： Dextran-hyaluronate (Dex-HA) based supermacroporous cryogel scaffolds for soft tissue engineering were prepared by free radical cryo-copolymerization of aqueous solutions containing the dextran methacrylate (Dex-MA) and hyaluronate methacrylate (HA-MA) at various macromonomer concentrations under the freezing condition. It was observed that the suitable total concentration of macromonomers for the preparation of Dex-HA cryogel scaffold with satisfied properties was 5% (w/w) at the HA-MA concentration of 1% (w/v), which was then used to produce the test scaffold. The obtained cryogel scaffold with 5% (w/w) macromonomer solution had high water permeability (5.1 × 10 m ) and high porosity (92.4%). The pore diameter examined by scanning electron microscopy (SEM) was in a broad range of 50–135 μm with the mean pore diameter of 91 μm. Furthermore, the cryogel scaffold also had good elastic nature with the elastic modulus of 17.47±1.44 kPa. The culture of 3T3-L1 preadipocyte within the scaffold was investigated and observed by SEM. Cells clustered on the pore walls and grew inside the scaffold indicating the Dex-HA cryogel scaffold could be a promising porous biomaterial for applications in tissue engineering.

关键词： cryogel scaffold tissue engineering dextran hyaluronate 3T3-L1 preadipocyte