2022 Issue 3 (Available Online: 2022-09-28)

    Zhao–Lin Zeng, Hui Xie
    2022, 3(3):  175-187.  doi:10.12336/biomatertransl.2022.03.002
    Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have great prospects for application in orthopaedic diseases by transporting substances such as proteins, lipids, and nucleic acids. The use of modified MSC-EVs combined with materials science can realise cell-free treatment of bone diseases.
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    Accumulating evidence suggests that the therapeutic role of mesenchymal stem cells (MSCs) in bone diseases is closely related to paracrine–generated extracellular vesicles (EVs). MSC–derived EVs (MSC–EVs) carry proteins, nucleic acids, and lipids to the extracellular space and affect the bone microenvironment. They have similar biological functions to MSCs, such as the ability to repair organ and tissue damage. In addition, MSC–EVs also have the advantages of long half–life, low immunogenicity, attractive stability, ability to pass through the blood–brain barrier, and demonstrate excellent performance with potential practical applications in bone diseases. In this review, we summarise the current applications and mechanisms of MSC–EVs in osteoporosis, osteoarthritis, bone tumours, osteonecrosis of the femoral head, and fractures, as well as the development of MSC–EVs combined with materials science in the field of orthopaedics. Additionally, we explore the critical challenges involved in the clinical application of MSC–EVs in orthopaedic diseases.

    Yiqiang Hu, Yuan Xiong, Ranyang Tao, Hang Xue, Lang Chen, Ze Lin, Adriana C. Panayi, Bobin Mi, Guohui Liu
    2022, 3(3):  188-200.  doi:10.12336/biomatertransl.2022.03.003
    Diabetic wound models are induced in different animals including rat, mouse, rabbit, pig, monkey, dog, cat and guinea pig with streptozotocin (STZ), high-fat diet (HFD) and alloxan. These diabetic wound models were used can be simulated the physiological mechanism of diabetic wounds, which providing a theory for translational research in treating diabetic wound healing.
    Abstract ( 282 )   HTML ( 33)   PDF (2004KB) ( 664 )  
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    Diabetic wounds are a common complication in diabetes patients. Due to peripheral nerve damage and vascular dysfunction, diabetic wounds are prone to progress to local ulcers, wound gangrene and even to require amputation, bringing huge psychological and economic burdens to patients. However, the current treatment methods for diabetic wounds mainly include wound accessories, negative pressure drainage, skin grafting and surgery; there is still no ideal treatment to promote diabetic wound healing at present. Appropriate animal models can simulate the physiological mechanism of diabetic wounds, providing a basis for translational research in treating diabetic wound healing. Although there are no animal models that can fully mimic the pathophysiological mechanisms of diabetic wounds in humans, it is vital to explore animal simulation models used in basic research and preclinical studies of diabetic wounds. In addition, hydrogel materials are regarded as a promising treatment for diabetic wounds because of their good antimicrobial activity, biocompatibility, biodegradation and appropriate mechanical properties. Herein, we review and discuss the different animal models used to investigate the pathological mechanisms of diabetic wounds. We further discuss the promising future application of hydrogel biomaterials in diabetic wound healing.

    Xin Huang, Haoyu Guo, Lutong Wang, Zengwu Shao
    2022, 3(3):  201-212.  doi:10.12336/biomatertransl.2022.03.004
    To investigate the development of engineered microorganism-based delivery systems for targeted cancer therapy, this review covers the main types and characteristics of microorganisms such as bacteria, viruses, fungi, microalgae, and their components. Moreover, innovative techniques and therapies such as chemotherapy, phototherapy, immunotherapy, radiotherapy, and oncolytic virotherapy are also discussed.
    Abstract ( 142 )   HTML ( 16)   PDF (1207KB) ( 341 )  
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    Microorganisms with innate and artificial advantages have been regarded as intelligent drug delivery systems for cancer therapy with the help of engineering technology. Although numerous studies have confirmed the promising prospects of microorganisms in cancer, several problems such as immunogenicity and toxicity should be addressed before further clinical applications. This review aims to investigate the development of engineered microorganism–based delivery systems for targeted cancer therapy. The main types of microorganisms such as bacteria, viruses, fungi, microalgae, and their components and characteristics are introduced in detail. Moreover, the engineering strategies and biomaterials design of microorganisms are further discussed. Most importantly, we discuss the innovative attempts and therapeutic effects of engineered microorganisms in cancer. Taken together, engineered microorganism–based delivery systems hold tremendous promise for biomedical applications in targeted cancer therapy.

    Chavee Laomeephol, Helena Ferreira, Sorada Kanokpanont, Jittima Amie Luckanagul, Nuno M Neves, Siriporn Damrongsakkul
    2022, 3(3):  213-220.  doi:10.12336/biomatertransl.2022.03.005
    Cell- and drug-loaded hydrogels were developed based on phospholipid-induced silk fibroin hydrogels to serve as scaffolds conforming to tissue-engineering concepts. The controlled release of drug loaded in the hydrogels was shown to promote the osteogenic differentiation of encapsulated cells. The dual encapsulation could synergise in enhancing cellular activities.
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    The tissue engineering triad comprises the combination of cells, scaffolds and biological factors. Therefore, we prepared cell– and drug–loaded hydrogels using in situ silk fibroin (SF) hydrogels induced by dimyristoyl glycerophosphoglycerol (DMPG). DMPG is reported to induce rapid hydrogel formation by SF, facilitating cell encapsulation in the hydrogel matrix while maintaining high cell viability and proliferative capacity. In addition, DMPG can be used for liposome formulations in entrapping drug molecules. Dexamethasone (Dex) was loaded into the DMPG–induced SF hydrogels together with human osteoblast–like SaOS–2 cells, then the osteogenic differentiation of the entrapped cells was evaluated in vitro and compared to cells cultured under standard conditions. Calcium production by cells cultured in DMPG/Dex–SF hydrogels with Dex–depleted osteogenic medium was equivalent to that of cells cultured in conventional osteogenic medium containing Dex. The extended–release of the entrapped Dex by the hydrogels was able to provide a sufficient drug amount for osteogenic induction. The controlled release of Dex was also advantageous for cell viability even though its dose in the hydrogels was far higher than that in osteogenic medium. The results confirmed the possibility of using DMPG–induced SF hydrogels to enable dual cell and drug encapsulation to fulfil the practical applications of tissue–engineered constructs.

    Monchupa Kingsak, Panita Maturavongsadit, Hong Jiang, Qian Wang
    2022, 3(3):  221-233.  doi:10.12336/biomatertransl.2022.03.006
    The comprehensive assessment of cell adhesion on well-defined and controllable titanium dioxide (TiO2) nanotube arrays with a wide range of pore sizes. An 80-nm pore size of TiO2 nanotube arrays (TNAs) showed a promising effect on cell adhesion, and pore sizes of 30 and 80 nm enhanced cell spreading and percentage cell area coverage.
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    Nanotopographical features can be beneficial in augmenting cell functions and increasing osteogenic potential. However, the relationships between surface topographies and biological responses are difficult to establish due to the difficulty in controlling the surface topographical features at a low–nanometre scale. Herein, we report the fabrication of well–defined controllable titanium dioxide (TiO2) nanotube arrays with a wide range of pore sizes, 30–175 nm in diameter, and use of the electrochemical anodization method to assess the effect of surface nanotopographies on cell morphology and adhesion. The results show that TiO2 nanotube arrays with pore sizes of 30 and 80 nm allowed for cell spreading of bone marrow–derived mesenchymal stem cells with increased cell area coverage. Additionally, cell adhesion was significantly enhanced by controlled nanotopographies of TiO2 nanotube arrays with 80 nm pore size. Our results demonstrate that surface modification at the nano–scale level with size tunability under controlled chemical/physical properties and culture conditions can greatly impact cell responses. These findings point to a new direction of material design for bone–tissue engineering in orthopaedic applications.