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    Recent updates on the biological basis of heterogeneity in bone marrow stromal cells/skeletal stem cells
    Deepika Arora, Pamela Gehron Robey
    Biomaterials Translational    2022, 3 (1): 3-16.   DOI: 10.12336/biomatertransl.2022.01.002
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    Based on studies over the last several decades, the self-renewing skeletal lineages derived from bone marrow stroma could be an ideal source for skeletal tissue engineering. However, the markers for osteogenic precursors; i.e., bone marrow-derived skeletal stem cells (SSCs), in association with other cells of the marrow stroma (bone marrow stromal cells, BMSCs) and their heterogeneous nature both in vivo and in vitro remain to be clarified. This review aims to highlight: i) the importance of distinguishing BMSCs/SSCs from other “mesenchymal stem/stromal cells”, and ii) factors that are responsible for their heterogeneity, and how these factors impact on the differentiation potential of SSCs towards bone. The prospective role of SSC enrichment, their expansion and its impact on SSC phenotype is explored. Emphasis has also been given to emerging single cell RNA sequencing approaches in scrutinizing the unique population of SSCs within the BMSC population, along with their committed progeny. Understanding the factors involved in heterogeneity may help researchers to improvise their strategies to isolate, characterize and adopt best culture practices and source identification to develop standard operating protocols for developing reproducible stem cells grafts. However, more scientific understanding of the molecular basis of heterogeneity is warranted that may be obtained from the robust high-throughput functional transcriptomics of single cells or clonal populations.

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    Mesenchymal stem cell differentiation and usage for biotechnology applications: tissue engineering and food manufacturing
    Dafna Benayahu
    Biomaterials Translational    2022, 3 (1): 17-23.   DOI: 10.12336/biomatertransl.2022.01.003
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    Recent advances in the field of stem cell research now enable their utilisation for biotechnology applications in regenerative medicine and food tech. The first use of stem cells as biomedical devices employed a combination of cells and scaffold to restore, improve, or replace damaged tissues and to grow new viable tissue for replacement organs. This approach has also been adopted to replace meat production in the food industry. Mesenchymal stem cells are the source material used to induce cells to differentiate into the desired lineage. These technologies require mass propagation and rely on supplying the regulatory factors that direct differentiation. Mesenchymal stem cells can differentiate into fibroblastic and skeletal cells; fibroblastic/chondrogenic/osteogenic/myogenic and adipogenic lineages. Each differentiation fate requires specific key molecular regulators and appropriate activation conditions. Stem cell commitment determination involves a concerted effort of coordinated activation and silencing of lineage-specific genes. Transcription factors which bind gene promoters and chromatin-remodelling proteins are key players in the control process of lineage commitment and differentiation from embryogenesis through adulthood. Consequently, a major research challenge is to characterise such molecular pathways that coordinate lineage-specific differentiation and function. Revealing the mechanisms of action and the main factors will provide the knowledge necessary to control activation and regulation to achieve a specific lineage. Growing cells on a scaffold is a support system that mimics natural tissue and transduces the appropriate signals of the tissue niche for appropriate cellular function. The outcome of such research will deepen the understanding of cell differentiation to promote and advance the biotech, allowing the cell expansion required for their usage in therapy or the development of food tech.

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    Oral stem cells, decoding and mapping the resident cells populations
    Xuechen Zhang, Ana Justo Caetano, Paul T. Sharpe, Ana Angelova Volponi
    Biomaterials Translational    2022, 3 (1): 24-30.   DOI: 10.12336/biomatertransl.2022.01.004
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    The teeth and their supporting tissues provide an easily accessible source of oral stem cells. These different stem cell populations have been extensively studied for their properties, such as high plasticity and clonogenicity, expressing stem cell markers and potency for multilineage differentiation in vitro. Such cells with stem cell properties have been derived and characterised from the dental pulp tissue, the apical papilla region of roots in development, as well as the supporting tissue of periodontal ligament that anchors the tooth within the alveolar socket and the soft gingival tissue. Studying the dental pulp stem cell populations in a continuously growing mouse incisor model, as a traceable in vivo model, enables the researchers to study the properties, origin and behaviour of mesenchymal stem cells. On the other side, the oral mucosa with its remarkable scarless wound healing phenotype, offers a model to study a well-coordinated system of healing because of coordinated actions between epithelial, mesenchymal and immune cells populations. Although described as homogeneous cell populations following their in vitro expansion, the increasing application of approaches that allow tracing of individual cells over time, along with single-cell RNA-sequencing, reveal that different oral stem cells are indeed diverse populations and there is a highly organised map of cell populations according to their location in resident tissues, elucidating diverse stem cell niches within the oral tissues. This review covers the current knowledge of diverse oral stem cells, focusing on the new approaches in studying these cells. These approaches “decode” and “map” the resident cells populations of diverse oral tissues and contribute to a better understanding of the “stem cells niche architecture and interactions. Considering the high accessibility and simplicity in obtaining these diverse stem cells, the new findings offer potential in development of translational tissue engineering approaches and innovative therapeutic solutions.

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    The long and winding road: homeostatic and disordered haematopoietic microenvironmental niches: a narrative review
    Suzanne M. Watt
    Biomaterials Translational    2022, 3 (1): 31-54.   DOI: 10.12336/biomatertransl.2022.01.005
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    Haematopoietic microenvironmental niches have been described as the ‘gatekeepers’ for the blood and immune systems. These niches change during ontogeny, with the bone marrow becoming the predominant site of haematopoiesis in post-natal life under steady state conditions. To determine the structure and function of different haematopoietic microenvironmental niches, it is essential to clearly define specific haematopoietic stem and progenitor cell subsets during ontogeny and to understand their temporal appearance and anatomical positioning. A variety of haematopoietic and non-haematopoietic cells contribute to haematopoietic stem and progenitor cell niches. The latter is reported to include endothelial cells and mesenchymal stromal cells (MSCs), skeletal stem cells and/or C-X-C motif chemokine ligand 12-abundant-reticular cell populations, which form crucial components of these microenvironments under homeostatic conditions. Dysregulation or deterioration of such cells contributes to significant clinical disorders and diseases worldwide and is associated with the ageing process. A critical appraisal of these issues and of the roles of MSC/C-X-C motif chemokine ligand 12-abundant-reticular cells and the more recently identified skeletal stem cell subsets in bone marrow haematopoietic niche function under homeostatic conditions and during ageing will form the basis of this research review. In the context of haematopoiesis, clinical translation will deal with lessons learned from the vast experience garnered from the development and use of MSC therapies to treat graft versus host disease in the context of allogeneic haematopoietic transplants, the recent application of these MSC therapies to treating emerging and severe coronavirus disease 2019 (COVID-19) infections, and, given that skeletal stem cell ageing is one proposed driver for haematopoietic ageing, the potential contributions of these stem cells to haematopoiesis in healthy bone marrow and the benefits and challenges of using this knowledge for rejuvenating the age-compromised bone marrow haematopoietic niches and restoring haematopoiesis.

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    An update of nanotopographical surfaces in modulating stem cell fate: a narrative review
    Shuqin Cao, Quan Yuan
    Biomaterials Translational    2022, 3 (1): 55-64.   DOI: 10.12336/biomatertransl.2022.01.006
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    Stem cells have been one of the ideal sources for tissue regeneration owing to their capability of self-renewal and differentiation. In vivo, the extracellular microenvironment plays a vital role in modulating stem cell fate. When developing biomaterials for regenerative medicine, incorporating biochemical and biophysical cues to mimic extracellular matrix can enhance stem cell lineage differentiation. More specifically, modulating the stem cell fate can be achieved by controlling the nanotopographic features on synthetic surfaces. Optimization of nanotopographical features leads to desirable stem cell functions, which can maximize the effectiveness of regenerative treatment. In this review, nanotopographical surfaces, including static patterned surface, dynamic patterned surface, and roughness are summarized, and their fabrication, as well as the impact on stem cell behaviour, are discussed. Later, the recent progress of applying nanotopographical featured biomaterials for altering different types of stem cells is presented, which directs the design and fabrication of functional biomaterial. Last, the perspective in fundamental research and for clinical application in this field is discussed.

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    Manufacturing artificial bone allografts: a perspective
    Emma Steijvers, Armaan Ghei, Zhidao Xia
    Biomaterials Translational    2022, 3 (1): 65-80.   DOI: 10.12336/biomatertransl.2022.01.007
    Abstract37)   HTML15)    PDF(pc) (1261KB)(52)       Save

    Bone grafts have traditionally come from four sources: the patients’ own tissue (autograft), tissue from a living or cadaveric human donor (allograft), animal donors (xenograft) and synthetic artificial biomaterials (ceramics, cement, polymers, and metal). However, all of these have advantages and drawbacks. The most commercially successful bone grafts so far are allografts, which hold 57% of the current bone graft market; however, disease transmission and scarcity are still significant drawbacks limiting their use. Tissue-engineered grafts have great potential, in which human stem cells and synthetical biomaterials are combined to produce bone-like tissue in vitro, but this is yet to be approved for widespread clinical practice. It is hypothesised that artificial bone allografts can be mass-manufactured to replace conventional bone allografts through refined bone tissue engineering prior to decellularisation. This review article aims to review current literature on (1) conventional bone allograft preparation; (2) bone tissue engineering including the use of synthetic biomaterials as bone graft substitute scaffolds, combined with osteogenic stem cells in vitro; (3) potential artificial allograft manufacturing processes, including mass production of engineered bone tissue, osteogenic enhancement, decellularisation, sterilisation and safety assurance for regulatory approval. From these assessments, a practical route map for mass production of artificial allografts for clinical use is proposed.

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    History, progress and future challenges of artificial blood vessels: a narrative review
    Ke Hu, Yuxuan Li, Zunxiang Ke, Hongjun Yang, Chanjun Lu, Yiqing Li, Yi Guo, Weici Wang
    Biomaterials Translational    2022, 3 (1): 81-98.   DOI: 10.12336/biomatertransl.2022.01.008
    Abstract61)   HTML9)    PDF(pc) (2405KB)(105)       Save

    Cardiovascular disease serves as the leading cause of death worldwide, with stenosis, occlusion, or severe dysfunction of blood vessels being its pathophysiological mechanism. Vascular replacement is the preferred surgical option for treating obstructed vascular structures. Due to the limited availability of healthy autologous vessels as well as the incidence of postoperative complications, there is an increasing demand for artificial blood vessels. From synthetic to natural, or a mixture of these components, numerous materials have been used to prepare artificial vascular grafts. Although synthetic grafts are more appropriate for use in medium to large-diameter vessels, they fail when replacing small-diameter vessels. Tissue-engineered vascular grafts are very likely to be an ideal alternative to autologous grafts in small-diameter vessels and are worthy of further investigation. However, a multitude of problems remain that must be resolved before they can be used in biomedical applications. Accordingly, this review attempts to describe these problems and provide a discussion of the generation of artificial blood vessels. In addition, we deliberate on current state-of-the-art technologies for creating artificial blood vessels, including advances in materials, fabrication techniques, various methods of surface modification, as well as preclinical and clinical applications. Furthermore, the evaluation of grafts both in vivo and in vitro, mechanical properties, challenges, and directions for further research are also discussed.

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    Mesenchymal stem cell-derived extracellular vesicles: a possible therapeutic strategy for orthopaedic diseases: a narrative review
    Zhao-Lin Zeng, Hui Xie
    Biomaterials Translational   
    Online available: 12 August 2022

    Human pluripotent stem cells: tools for regenerative medicine
    Peter W. Andrews
    Biomaterials Translational    2021, 2 (4): 294-300.   DOI: 10.12336/biomatertransl.2021.04.004
    Abstract149)   HTML31)    PDF(pc) (247KB)(222)       Save

    Human embryonic stem cells and induced pluripotent stem cells, together denoted as pluripotent stem cells have opened up unprecedented opportunities for developments in human healthcare over the past 20 years. Although much about the properties and behaviour of these cells required to underpin their applications has been discovered over this time, a number of issues remain. This brief review considers the history of these developments and some of the underlying biology, pointing out some of the problems still to be resolved, particularly in relation to their genetic stability and possible malignancy.

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    Adipose-derived cells: building blocks of three-dimensional microphysiological systems
    Trivia P. Frazier, Katie Hamel, Xiying Wu, Emma Rogers, Haley Lassiter, Jordan Robinson, Omair Mohiuddin, Michael Henderson, Jeffrey M. Gimble
    Biomaterials Translational    2021, 2 (4): 301-306.   DOI: 10.12336/biomatertransl.2021.04.005
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    Microphysiological systems (MPS) created with human-derived cells and biomaterial scaffolds offer a potential in vitro alternative to in vivo animal models. The adoption of three-dimensional MPS models has economic, ethical, regulatory, and scientific implications for the fields of regenerative medicine, metabolism/obesity, oncology, and pharmaceutical drug discovery. Key opinion leaders acknowledge that MPS tools are uniquely positioned to aid in the objective to reduce, refine, and eventually replace animal experimentation while improving the accuracy of the finding’s clinical translation. Adipose tissue has proven to be an accessible and available source of human-derived stromal vascular fraction (SVF) cells, a heterogeneous population available at point of care, and adipose-derived stromal/stem cells, a relatively homogeneous population requiring plastic adherence and culture expansion of the SVF cells. The adipose-derived stromal/stem cells or SVF cells, in combination with human tissue or synthetic biomaterial scaffolds, can be maintained for extended culture periods as three-dimensional MPS models under angiogenic, stromal, adipogenic, or osteogenic conditions. This review highlights recent literature relating to the versatile use of adipose-derived cells as fundamental components of three-dimensional MPS models for discovery research and development. In this context, it compares the merits and limitations of the adipose-derived stromal/stem cells relative to SVF cell models and considers the likely directions that this emerging field of scientific discovery will take in the near future.

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    Mesenchymal stem cells and COVID-19: the process of discovery and of translation
    Arnold I. Caplan
    Biomaterials Translational    2021, 2 (4): 307-311.   DOI: 10.12336/biomatertransl.2021.04.006
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    Mesenchymal stem cells were developed as a cell-based therapeutic in the 1990’s. The translation of culture expanded mesenchymal stem cells from a basic science focus into a modern therapeutic has taken 30 years. The current state of the basic science information argues that mesenchymal stem cells may be curative for coronavirus disease 2019 (COVID-19). Indeed, early small-scale clinical trials have shown positive results. The issue raised is how to assemble the resources to get this cell-based therapy approved for clinical use. The technology is complex, the COVID-19 viral infections are life threatening, the cost is high, but human life is precious. What will it take to perfect this potentially curative technology?

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    Cellular modulation by the mechanical cues from biomaterials for tissue engineering
    Qiang Wei, Shenghao Wang, Feng Han, Huan Wang, Weidong Zhang, Qifan Yu, Changjiang Liu, Luguang Ding, Jiayuan Wang, Lili Yu, Caihong Zhu, Bin Li
    Biomaterials Translational    2021, 2 (4): 323-342.   DOI: 10.12336/biomatertransl.2021.04.001
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    Mechanical cues from the extracellular matrix (ECM) microenvironment are known to be significant in modulating the fate of stem cells to guide developmental processes and maintain bodily homeostasis. Tissue engineering has provided a promising approach to the repair or regeneration of damaged tissues. Scaffolds are fundamental in cell-based regenerative therapies. Developing artificial ECM that mimics the mechanical properties of native ECM would greatly help to guide cell functions and thus promote tissue regeneration. In this review, we introduce various mechanical cues provided by the ECM including elasticity, viscoelasticity, topography, and external stimuli, and their effects on cell behaviours. Meanwhile, we discuss the underlying principles and strategies to develop natural or synthetic biomaterials with different mechanical properties for cellular modulation, and explore the mechanism by which the mechanical cues from biomaterials regulate cell function toward tissue regeneration. We also discuss the challenges in multimodal mechanical modulation of cell behaviours and the interplay between mechanical cues and other microenvironmental factors.

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    Endogenous repair theory enriches construction strategies for orthopaedic biomaterials: a narrative review
    Yizhong Peng, Jinye Li, Hui Lin, Shuo Tian, Sheng Liu, Feifei Pu, Lei Zhao, Kaige Ma, Xiangcheng Qing, Zengwu Shao
    Biomaterials Translational    2021, 2 (4): 343-360.   DOI: 10.12336/biomatertransl.2021.04.008
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    The development of tissue engineering has led to new strategies for mitigating clinical problems; however, the design of the tissue engineering materials remains a challenge. The limited sources and inadequate function, potential risk of microbial or pathogen contamination, and high cost of cell expansion impair the efficacy and limit the application of exogenous cells in tissue engineering. However, endogenous cells in native tissues have been reported to be capable of spontaneous repair of the damaged tissue. These cells exhibit remarkable plasticity, and thus can differentiate or be reprogrammed to alter their phenotype and function after stimulation. After a comprehensive review, we found that the plasticity of these cells plays a major role in establishing the cell source in the mechanism involved in tissue regeneration. Tissue engineering materials that focus on assisting and promoting the natural self-repair function of endogenous cells may break through the limitations of exogenous seed cells and further expand the applications of tissue engineering materials in tissue repair. This review discusses the effects of endogenous cells, especially stem cells, on injured tissue repairing, and highlights the potential utilisation of endogenous repair in orthopaedic biomaterial constructions for bone, cartilage, and intervertebral disc regeneration.

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    Experimental and computational models for tissue-engineered heart valves: a narrative review
    Ge Yan, Yuqi Liu, Minghui Xie, Jiawei Shi, Weihua Qiao, Nianguo Dong
    Biomaterials Translational    2021, 2 (4): 361-375.   DOI: 10.12336/biomatertransl.2021.04.009
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    Valvular heart disease is currently a common problem which causes high morbidity and mortality worldwide. Prosthetic valve replacements are widely needed to correct narrowing or backflow through the valvular orifice. Compared to mechanical valves and biological valves, tissue-engineered heart valves can be an ideal substitute because they have a low risk of thromboembolism and calcification, and the potential for remodelling, regeneration, and growth. In order to test the performance of these heart valves, various animal models and other models are needed to optimise the structure and function of tissue-engineered heart valves, which may provide a potential mechanism responsible for substantial enhancement in tissue-engineered heart valves. Choosing the appropriate model for evaluating the performance of the tissue-engineered valve is important, as different models have their own advantages and disadvantages. In this review, we summarise the current state-of-the-art animal models, bioreactors, and computational simulation models with the aim of creating more strategies for better development of tissue-engineered heart valves. This review provides an overview of major factors that influence the selection and design of a model for tissue-engineered heart valve. Continued efforts in improving and testing models for valve regeneration remain crucial in basic science and translational researches. Future research should focus on finding the right animal model and developing better in vitro testing systems for tissue-engineered heart valve.

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    Advances and perspective on the translational medicine of biodegradable metals
    Hongtao Yang, Wenjiao Lin, Yufeng Zheng
    Biomaterials Translational    2021, 2 (3): 177-187.   DOI: 10.12336/biomatertransl.2021.03.002
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    Biodegradable metals, designed to be safely degraded and absorbed by the body after fulfil the intended functions, are of particular interest in the 21st century. The marriage of advanced biodegradable metals with clinical needs have yield unprecedented possibility. Magnesium, iron, and zinc-based materials constitute the main components of temporary, implantable metallic medical devices. A burgeoning number of studies on biodegradable metals have driven the clinical translation of biodegradable metallic devices in the fields of cardiology and orthopaedics over the last decade. Their ability to degrade as well as their beneficial biological functions elicited during degradation endow this type of material with the potential to shift the paradigm in the treatment of musculoskeletal and cardiovascular diseases. This review provides an insight into the degradation mechanism of these metallic devices in specific application sites and introduces state-of-the-art translational research in the field of biodegradable metals, as well as highlighting some challenges for materials design strategies in the context of mechanical and biological compatibility.

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    Update on the research and development of magnesium-based biodegradable implants and their clinical translation in orthopaedics
    Ying Luo, Jue Wang, Michael Tim Yun Ong, Patrick Shu-hang Yung, Jiali Wang, Ling Qin
    Biomaterials Translational    2021, 2 (3): 188-196.   DOI: 10.12336/biomatertransl.2021.03.003
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    Biodegradable magnesium (Mg) or its alloys are desirable materials for development into new-generation internal fixation devices or implants with high biocompatibility, adequate mechanical modulus, and osteopromotive properties, which may overcome some of the drawbacks of the existing permanent orthopaedic implants with regard to stress-shielding of bone and beam-hardening effects on radiographic images. This review summarises the current research status of Mg-based orthopaedic implants in animals and clinical trials. First, detailed information of animal studies including bone fracture repair and anterior cruciate ligament reconstruction with the use of Mg-based orthopaedic devices is introduced. Second, the repair mechanisms of the Mg-based orthopaedic implants are also reviewed. Afterwards, reports of recent clinical cases treated using Mg-based implants in orthopaedics are summarised. Finally, the challenges and the strategies of the use of Mg-based orthopaedic implants are discussed. Taken together, the collected efforts in basic research, translational work, and clinical applications of Mg-based orthopaedic implants over the last decades greatly contribute to the development of a new generation of biodegradable metals used for the design of innovative implants for better treatment of orthopaedic conditions in patients with challenging skeletal disorders or injuries.

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    Magnesium-based materials in orthopaedics: material properties and animal models
    Xirui Jing, Qiuyue Ding, Qinxue Wu, Weijie Su, Keda Yu, Yanlin Su, Bing Ye, Qing Gao, Tingfang Sun, Xiaodong Guo
    Biomaterials Translational    2021, 2 (3): 197-213.   DOI: 10.12336/biomatertransl.2021.03.004
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    As a new generation of medical metal materials, degradable magnesium-based materials have excellent mechanical properties and osteogenic promoting ability, making them promising materials for the treatment of refractory bone diseases. Animal models can be used to understand and evaluate the performance of materials in complex physiological environments, providing relevant data for preclinical evaluation of implants and laying the foundation for subsequent clinical studies. To date, many researchers have studied the biocompatibility, degradability and osteogenesis of magnesium-based materials, but there is a lack of review regarding the effects of magnesium-based materials in vivo. In view of the growing interest in these materials, this review briefly describes the properties of magnesium-based materials and focuses on the safety and efficacy of magnesium-based materials in vivo. Various animal models including rats, rabbits, dogs and pigs are covered to better understand and evaluate the progress and future of magnesium-based materials. This literature analysis reveals that the magnesium-based materials have good biocompatibility and osteogenic activity, thus causing no adverse reaction around the implants in vivo, and that they exhibit a beneficial effect in the process of bone repair. In addition, the degradation rate in vivo can also be improved by means of alloying and coating. These encouraging results show a promising future for the use of magnesium-based materials in musculoskeletal disorders.

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    Biodegradable magnesium alloys for orthopaedic applications
    Yu Lu, Subodh Deshmukh, Ian Jones, Yu-Lung Chiu
    Biomaterials Translational    2021, 2 (3): 214-235.   DOI: 10.12336/biomatertransl.2021.03.005
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    There is increasing interest in the development of bone repair materials for biomedical applications. Magnesium (Mg)-based alloys have a natural ability to biodegrade because they corrode in aqueous media; they are thus promising materials for orthopaedic device applications in that the need for a secondary surgical operation to remove the implant can be eliminated. Notably, Mg has superior biocompatibility because Mg is found in the human body in abundance. Moreover, Mg alloys have a low elastic modulus, close to that of natural bone, which limits stress shielding. However, there are still some challenges for Mg-based fracture fixation. The degradation of Mg alloys in biological fluids can be too rapid, resulting in a loss of mechanical integrity before complete healing of the bone fracture. In order to achieve an appropriate combination of bio-corrosion and mechanical performance, the microstructure needs to be tailored properly by appropriate alloy design, as well as the use of strengthening processes and manufacturing techniques. This review covers the evolution, current strategies and future perspectives of Mg-based orthopaedic implants.

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    Research and development strategy for biodegradable magnesium-based vascular stents: a review
    Jialin Niu, Hua Huang, Jia Pei, Zhaohui Jin, Shaokang Guan, Guangyin Yuan
    Biomaterials Translational    2021, 2 (3): 236-247.   DOI: 10.12336/biomatertransl.2021.03.06
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    Magnesium alloys are an ideal material for biodegradable vascular stents, which can be completely absorbed in the human body, and have good biosafety and mechanical properties. However, the rapid corrosion rate and excessive localized corrosion, as well as challenges in the preparation and processing of microtubes for stents, are restricting the clinical application of magnesium-based vascular stents. In the present work we will give an overview of the recent progresses on biodegradable magnesium based vascular stents including magnesium alloy design, high-precision microtubes processing, stent shape optimisation and functional coating preparation. In particular, the Triune Principle in biodegradable magnesium alloy design is proposed based on our research experience, which requires three key aspects to be considered when designing new biodegradable magnesium alloys for vascular stents application, i.e. biocompatibility and biosafety, mechanical properties, and biodegradation. This review hopes to inspire the future studies on the design and development of biodegradable magnesium alloy-based vascular stents.

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    Biofunctional magnesium coating of implant materials by physical vapour deposition
    Qingchuan Wang, Weidan Wang, Yanfang Li, Weirong Li, Lili Tan, Ke Yang
    Biomaterials Translational    2021, 2 (3): 248-256.   DOI: 10.12336/biomatertransl.2021.03.007
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    The lack of bioactivity of conventional medical materials leads to low osseointegration ability that may result in the occurrence of aseptic loosening in the clinic. To achieve high osseointegration, surface modifications with multiple biofunctions including degradability, osteogenesis, angiogenesis and antibacterial properties are required. However, the functions of conventional bioactive coatings are limited. Thus novel biofunctional magnesium (Mg) coatings are believed to be promising candidates for surface modification of implant materials for use in bone tissue repair. By physical vapour deposition, many previous researchers have deposited Mg coatings with high purity and granular microstructure on titanium alloys, polyetheretherketone, steels, Mg alloys and silicon. It was found that the Mg coatings with high-purity could considerably control the degradation rate in the initial stage of Mg alloy implantation, which is the most important problem for the application of Mg alloy implants. In addition, Mg coating on titanium (Ti) implant materials has been extensively studied both in vitro and in vivo, and the results indicated that their corrosion behaviour and biocompatibility are promising. Mg coatings continuously release Mg ions during the degradation process, and the alkaline environment caused by Mg degradation has obvious antibacterial effects. Meanwhile, the Mg coating has beneficial effects on osteogenesis and osseointegration, and increases the new bone-regenerating ability. Mg coatings also exhibit favourable osteogenic and angiogenic properties in vitro and increased long-term bone formation and early vascularization in vivo. Inhibitory effects of Mg coatings on osteoclasts have also been proven, which play a great role in osteoporotic patients. In addition, in order to obtain more biofunctions, other alloying elements such as copper have been added to the Mg coatings. Thus, Mg-coated Ti acquired biofunctions including degradability, osteogenesis, angiogenesis and antibacterial properties. These novel multi-functional Mg coatings are expected to significantly enhance the long-term safety of bone implants for the benefit of patients. This paper gives a brief review of studies of the microstructure, degradation behaviours and biofunctions of Mg coatings, and directions for future research are also proposed.

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    In silico modelling of the corrosion of biodegradable magnesium-based biomaterials: modelling approaches, validation and future perspectives
    Aditya Joshi, George Dias, Mark P. Staiger
    Biomaterials Translational    2021, 2 (3): 257-271.   DOI: 10.12336/biomatertransl.2021.03.008
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    Metallic biomedical implants based on magnesium, zinc and iron alloys have emerged as bioresorbable alternatives to permanent orthopaedic implants over the last two decades. The corrosion rate of biodegradable metals plays a critical role in controlling the compatibility and functionality of the device in vivo. The broader adoption of biodegradable metals in orthopaedic applications depends on developing in vitro methods that accurately predict the biodegradation behaviour in vivo. However, the physiological environment is a highly complex corrosion environment to replicate in the laboratory, making the in vitro-to-in vivo translation of results very challenging. Accordingly, the results from in vitro corrosion tests fail to provide a complete schema of the biodegradation behaviour of the metal in vivo. In silico approach based on computer simulations aim to bridge the observed differences between experiments performed in vitro and vivo. A critical review of the state-of-the-art of computational modelling techniques for predicting the corrosion behaviour of magnesium alloy as a biodegradable metal is presented.

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    Proper animal experimental designs for preclinical research of biomaterials for intervertebral disc regeneration
    Yizhong Peng, Xiangcheng Qing, Hongyang Shu, Shuo Tian, Wenbo Yang, Songfeng Chen, Hui Lin, Xiao Lv, Lei Zhao, Xi Chen, Feifei Pu, Donghua Huang, Xu Cao, Zengwu Shao
    Biomaterials Translational    2021, 2 (2): 91-142.   DOI: 10.12336/biomatertransl.2021.02.003
    Abstract496)   HTML63)    PDF(pc) (3328KB)(553)       Save

    Low back pain is a vital musculoskeletal disease that impairs life quality, leads to disability and imposes heavy economic burden on the society, while it is greatly attributed to intervertebral disc degeneration (IDD). However, the existing treatments, such as medicines, chiropractic adjustments and surgery, cannot achieve ideal disc regeneration. Therefore, advanced bioactive therapies are implemented, including stem cells delivery, bioreagents administration, and implantation of biomaterials etc. Among these researches, few reported unsatisfying regenerative outcomes. However, these advanced therapies have barely achieved successful clinical translation. The main reason for the inconsistency between satisfying preclinical results and poor clinical translation may largely rely on the animal models that cannot actually simulate the human disc degeneration. The inappropriate animal model also leads to difficulties in comparing the efficacies among biomaterials in different reaches. Therefore, animal models that better simulate the clinical charateristics of human IDD should be acknowledged. In addition, in vivo regenerative outcomes should be carefully evaluated to obtain robust results. Nevertheless, many researches neglect certain critical characteristics, such as adhesive properties for biomaterials blocking annulus fibrosus defects and hyperalgesia that is closely related to the clinical manifestations, e.g., low back pain. Herein, in this review, we summarized the animal models established for IDD, and highlighted the proper models and parameters that may result in acknowledged IDD models. Then, we discussed the existing biomaterials for disc regeneration and the characteristics that should be considered for regenerating different parts of discs. Finally, well-established assays and parameters for in vivo disc regeneration are explored.

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    Physicochemical properties of respiratory droplets and their role in COVID-19 pandemics: a critical review
    Ting Ge, Shengfeng Cheng
    Biomaterials Translational    2021, 2 (1): 10-18.   DOI: 10.3877/cma.j.issn.2096-112X.2021.01.003
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    The ongoing coronavirus disease 2019 (COVID-19) pandemic is a serious challenge faced by the global community. Physical scientists can help medical workers and biomedical scientists, engineers, and practitioners, who are working on the front line, to slow down and eventually contain the spread of the COVID-19 virus. This review is focused on the physicochemical characteristics, including composition, aerodynamics, and drying behavior of respiratory droplets as a complex and multicomponent soft matter system, which are the main carrier of the virus for interpersonal transmission. The distribution and dynamics of virus particles within a droplet are also discussed. Understanding the characteristics of virus-laden respiratory droplets can lead to better design of personal protective equipment, frequently touched surfaces such as door knobs and touchscreens, and filtering equipment for indoor air circulation. Such an understanding also provides the scientific basis of public policy, including social distancing rules and public hygiene guidelines, implemented by governments around the world.

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    Recombinant adeno-associated virus-based gene therapy combined with tissue engineering for musculoskeletal regenerative medicine
    Yiqing Wang, Xiangyu Chu, Bing Wang
    Biomaterials Translational    2021, 2 (1): 19-29.   DOI: 10.3877/cma.j.issn.2096-112X.2021.01.004
    Abstract311)   HTML48)    PDF(pc) (670KB)(532)       Save

    Recombinant adeno-associated viral (rAAV) vector-mediated gene delivery is a novel molecular therapeutic approach for musculoskeletal disorders which achieves tissue regeneration by delivering a transgene to the impaired tissue. In recent years, substantial scientific progress in rAAV gene therapy has led to several clinical trials for human musculoskeletal diseases. Nevertheless, there are still limitations in developing an optimal gene therapy model due to the low transduction efficiency and fast degradation of the gene vectors. To overcome the challenges of rAAV gene therapy, tissue engineering combined with gene therapy has emerged as a more promising alternative. An rAAV viral vector incorporated into a biomaterial has a more controlled gene expression, lower immune response, and higher efficiency. A number of biomaterials and architectures have been combined with rAAV viral vectors, each having its own advantages and limitations. This review aims to give a broad introduction to combinatorial therapy and the recent progress this new technology has offered.

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    A biomaterials viewpoint for the 2020 SARS-CoV-2 vaccine development
    Isak Jatoi, Jingyu Fan
    Biomaterials Translational    2021, 2 (1): 30-42.   DOI: 10.3877/cma.j.issn.2096-112X.2021.01.005
    Abstract380)   HTML32)    PDF(pc) (1112KB)(649)       Save

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a considerable loss of life, morbidity, and economic distress since its emergence in late 2019. In response to the novel virus, public and private institutions around the world have utilized novel technologies to develop a vaccine in the hopes of building herd immunity and ending the pandemic. This review provides an overview of mechanisms and available data on the nascent vaccine technologies undergoing clinical trials to combat SARS-CoV-2, namely, those using protein subunits, viral vectors, mRNA, and DNA. Furthermore, we discuss the potential uses of biomaterials in improving the immunogenicity and safety of these vaccine technologies with the goal of improving upon newly-available technologies to combat future SARS-CoV-2 strains and other emerging viral pathogens.

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    Engineering immune-responsive biomaterials for skin regeneration
    Pingli Wu, Yangyang Liang, Guoming Sun
    Biomaterials Translational    2021, 2 (1): 61-71.   DOI: 10.3877/cma.j.issn.2096-112X.2021.01.008
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    The progress of biomaterials and tissue engineering has led to significant advances in wound healing, but the clinical therapy to regenerate perfect skin remains a great challenge. The implantation of biomaterial scaffolds to heal wounds inevitably leads to a host immune response. Many recent studies revealed that the immune system plays a significant role in both the healing process and the outcome. Immunomodulation or immuno-engineering has thus become a promising approach to develop pro-regenerative scaffolds for perfect skin regeneration. In this paper, we will review recent advancements in immunomodulating biomaterials in the field of skin repair and regeneration, and discuss strategies to modulate the immune response by tailoring the chemical, physical and biological properties of the biomaterials. Understanding the important role of immune responses and manipulating the inherent properties of biomaterials to regulate the immune reaction are approaches to overcome the current bottleneck of skin repair and regeneration.

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    Development of porphyrin and titanium dioxide sonosensitizers for sonodynamic cancer therapy
    Xiangyu Deng, Zengwu Shao, Yanli Zhao
    Biomaterials Translational    2021, 2 (1): 72-85.   DOI: 10.3877/cma.j.issn.2096-112X.2021.01.009
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    Sonodynamic therapy for malignant tumours has gained much attention for its deep penetration effect and efficient tumour killing ability. The design, modification, and utilization of sonosensitizers are important aspects of sonodynamic therapy. As an essential factor in this process, highly effective sonosensitizers should be developed to facilitate the clinical applications of sonodynamic therapy. This review takes porphyrin- and titanium dioxide (TiO2)-based systems as representative organic and inorganic sonosensitizers respectively, and summarizes their characteristics and biological effects as sonodynamic therapy. Upon discovery of novel sonosensitizers, sonodynamic therapy becomes an efficient means of adjuvant therapy for the treatment of malignant tumours.

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    Osteochondral scaffolds for early treatment of cartilage defects in osteoarthritic joints: from bench to clinic
    Maryam Tamaddon, Helena Gilja, Ling Wang, J. Miguel Oliveira, Xiaodan Sun, Rongwei Tan, Chaozong Liu
    Biomaterials Translational    2020, 1 (1): 3-17.   DOI: 10.3877/cma.j.issn.2096-112X.2020.01.002
    Abstract643)   HTML94)    PDF(pc) (1991KB)(938)       Save

    Osteoarthritis is a degenerative joint disease, typified by the loss in the quality of cartilage and bone at the interface of a synovial joint, resulting in pain, stiffness and reduced mobility. The current surgical treatment for advanced stages of the disease is joint replacement, where the non-surgical therapeutic options or less invasive surgical treatments are no longer effective. These are major surgical procedures which have a substantial impact on patients’ quality of life and lifetime risk of requiring revision surgery. Treatments using regenerative methods such as tissue engineering methods have been established and are promising for the early treatment of cartilage degeneration in osteoarthritis joints. In this approach, 3-dimensional scaffolds (with or without cells) are employed to provide support for tissue growth. However, none of the currently available tissue engineering and regenerative medicine products promotes satisfactory durable regeneration of large cartilage defects. Herein, we discuss the current regenerative treatment options for cartilage and osteochondral (cartilage and underlying subchondral bone) defects in the articulating joints. We further identify the main hurdles in osteochondral scaffold development for achieving satisfactory and durable regeneration of osteochondral tissues. The evolution of the osteochondral scaffolds - from monophasic to multiphasic constructs - is overviewed and the osteochondral scaffolds that have progressed to clinical trials are examined with respect to their clinical performances and their potential impact on the clinical practices. Development of an osteochondral scaffold which bridges the gap between small defect treatment and joint replacement is still a grand challenge. Such scaffold could be used for early treatment of cartilage and osteochondral defects at early stage of osteoarthritis and could either negate or delay the need for joint replacements.

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    One-dimensional micro/nanomotors for biomedicine: delivery, sensing and surgery
    Jiawang Guo, Yuan Lin
    Biomaterials Translational    2020, 1 (1): 18-32.   DOI: 10.3877/cma.j.issn.2096-112X.2020.01.003
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    The rapid development of artificial micro/nanomachines brings promising strategies to overcome challenges in biomedicine, including delivery, sensing and surgery. One-dimensional (1D) micro/nanomotors are one of the most attractive micro/nanomachines due to their high specific surface area, powerful impetus and weak rotation diffusion. In this review, different propulsion mechanisms and motion control strategies of 1D micro/nanomotors are summarized, and recent efforts towards their fabrication methods and biomedical applications are discussed. We envision the multidisciplinary research efforts in the field of 1D micro/nanomotors will pave their way to practical applications in bioimaging and biomedicine.

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    Segmental long bone regeneration guided by degradable synthetic polymeric scaffolds
    Xiaowen Xu, Jie Song
    Biomaterials Translational    2020, 1 (1): 33-45.   DOI: 10.3877/cma.j.issn.2096-112X.2020.01.004
    Abstract617)   HTML48)    PDF(pc) (2338KB)(582)       Save

    Recent developments in synthetic bone grafting materials and adjuvant therapeutic agents have opened the door to the regenerative reconstruction of critical-size long bone segmental defects resulting from trauma, osteoporotic fractures or tumour resections. Polymeric scaffolds with controlled macroporosities, degradability, useful surgical handling characteristics, and the ability to deliver biotherapeutics to promote new bone ingrowth have been developed for this challenging orthopaedic application. This review highlights major classes of degradable synthetic polymers and their biomineral composites, including conventional and amphiphilic polyesters, polyanhydrides, polycarbonates, and polyethylene glycol-based hydrogels, that have been explored for the regenerative reconstruction of critical-size long bone segmental defects over the past two decades. The pros and cons of these synthetic scaffold materials are presented in the context of enabling or impeding the functional (mechanical and radiographic) repair of a long bone segmental defect, with the long bone regeneration outcomes compared with healthy long bone controls or results achieved with current grafting standards.

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    Hydroxyethyl starch and its derivatives as nanocarriers for delivery of diagnostic and therapeutic agents towards cancers
    Ronghua Tan, Ying Wan, Xiangliang Yang
    Biomaterials Translational    2020, 1 (1): 46-57.   DOI: 10.3877/cma.j.issn.2096-112X.2020.01.005
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    Many types of drugs and agents used for cancer diagnosis and therapy often have low bioavailability and insufficient efficacy, as well as causing various side effects due to their nonspecific delivery. Nanocarriers with purposely-designed compositions and structures have shown varying degrees of abilities to deliver these compounds towards cancers in passive or active manners. Despite the availability of a variety of materials for the construction of nanocarriers, natural polymers with good biocompatibility and biodegradability are preferable for such usage because of their high in vivo safety as well as easy removal of degradation products. Among the natural polymers intended for building nanocarriers, hydroxyethyl starch and its derivatives have gained tremendous attention in the field of drug delivery in the form of nanomedicines over the last decade. There is growing optimism that ever more hydroxyethyl starch-based nanomedicines will be a significant addition to the armoury currently used for cancer diagnosis and therapy.

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    Nanoparticles and their effects on differentiation of mesenchymal stem cells
    Xing Yang, Yuanyuan Li, Xujie Liu, Wei He, Qianli Huang, Qingling Feng
    Biomaterials Translational    2020, 1 (1): 58-68.   DOI: 10.3877/cma.j.issn.2096-112X.2020.01.006
    Abstract280)   HTML32)    PDF(pc) (575KB)(296)       Save

    Over the past decades, advancements in nanoscience and nanotechnology have resulted in numerous nanomedicine platforms. Various nanoparticles, which exhibit many unique properties, play increasingly important roles in the field of biomedicine to realize the potential of nanomedicine. Due to the capacity of self-renewal and multilineage mesenchymal differentiation, mesenchymal stem cells (MSCs) have been widely used in the area of regenerative medicine and in clinical applications due to their potential to differentiate into various lineages. There are several factors that impact the differentiation of MSCs into different lineages. Many types of biomaterials such as polymers, ceramics, and metals are commonly applied in tissue engineering and regenerative therapies, and they are continuously refined over time. In recent years, along with the rapid development of nanotechnology and nanomedicine, nanoparticles have been playing more and more important roles in the fields of biomedicine and bioengineering. The combined use of nanoparticles and MSCs in biomedicine requires greater knowledge of the effects of nanoparticles on MSCs. This review focuses on the effects of four inorganic or metallic nanoparticles (hydroxyapatite, silica, silver, and calcium carbonate), which are widely used as biomaterials, on the osteogenic and adipogenic differentiation of MSCs. In this review, the cytotoxicity of these four nanoparticles, their effects on osteogenic/adipogenic differentiation of MSCs and the signalling pathways or transcription factors involved are summarized. In addition, the chemical composition, size, shape, surface area, surface charge and surface chemistry of nanoparticles, have been reported to impact cellular behaviours. In this review, we particularly emphasize the influence of their size on cellular responses. We envision our review will provide a theoretical basis for the combined application of MSCs and nanoparticles in biomedicine.

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