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BACKGROUND: In cartilage degeneration in osteoarthritis, cytokines and signaling pathways that target chondrocytes play an important role. OBJECTIVE: To review the latest research progress of osteoarthritis related cytokines and signaling pathways in recent years, such as the mechanism of action and treatment modalities, in order to provide a basis for future exploration of new therapeutic targets and modalities. METHODS: Literature search was conducted on CNKI, WanFang, VIP, PubMed, Web of Science, and Medline databases. Chinese search terms were “osteoarthritis, cytokines, signal pathway, chondrocyte, inflammation, treatment”. Finally, 60 papers were included for review. RESULTS AND CONCLUSION: (1) In current studies, it is believed that the specific mechanism of osteoarthritis is not clear, and a large number of studies have shown that osteoarthritis is strongly associated with cytokines and signaling pathways, which is a complex process of action. Relevant studies taking cytokines and signaling pathways as therapeutic breakthroughs are also the current hot spot. (2) The receptor antagonists of pro-inflammatory factors such as interleukin 1 are not effective in the treatment of osteoarthritis, and more studies turn to gene therapy. (3) The therapeutic methods of transforming growth factor β, recombinant factors of Wnt signaling pathway, gene therapy and mesenchymal stem cells have obtained positive research results. However, basic and clinical studies on safety and efficacy are likely to be conducted in future studies. (4) At present, relevant therapeutic methods such as platelet-rich plasma have been widely used in clinical practice, while recombinant factor, gene therapy and mesenchymal stem cell therapy are all in the research stage, among which mesenchymal stem cell therapy and gene therapy are expected to make breakthroughs in the field of cartilage repair and regeneration, and are worthy of expectation in the future. However, more clinical and basic studies are needed to verify its effectiveness and safety, explore its mechanism of action and scope of application, and set standards for its clinical use. [ABSTRACT FROM AUTHOR]

BACKGROUND: Currently, electrospun nanofibers, which are biomimetic materials of natural extracellular matrix and contain a three-dimensional network of interconnected pores, have been successfully used as scaffolds for various tissue regeneration, but are still faced with the challenge of extending the biomaterials into three-dimensional structures to reproduce the physiological, chemical as well as mechanical properties of the tissue microenvironment. OBJECTIVE: To summarize the process and principles of electrostatic spinning and to explore the applications of the resulting electrospun nanofibers in tissue regeneration of skin, blood vessels, nerves, bone, cartilage and tendons/ligaments. METHODS: With “electrospinning, electrospun nanofibers, electrospun nanofiber scaffolds, tissue regeneration” as the Chinese and English search terms, Google Academic Database, PubMed, and CNKI were searched, and finally 88 articles were included for review. RESULTS AND CONCLUSION: (1) The electrospun nanofibers are a natural fibrous extracellular matrix mimetic material and contain a three-dimensional network of interconnected pores that have been successfully used as scaffolds for a variety of tissue regeneration applications. (2) Several papers have described the great potential of electrospun nanofiber scaffolds applied to the regeneration of skin, blood vessels, nerves, bones, cartilage and tendons/ ligaments, providing a solid theoretical basis for its final application in clinical disease treatment, or for its transformation into practical products to enter the market. (3) However, the current research results are mostly based on cell experimental research results in vitro, and whether it can be finally applied to human body still needs clinical verification. (4) At present, many kinds of electrospun products for various clinical needs have been commercialized in and outside China, indicating that the research field of electrospun nanofiber scaffolds for soft and hard tissue regeneration has great research value and application potential. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ischemic stroke is one of the main causes of death and long-term disability, and the incidence is still rising year by year, seriously affecting the quality of life. Blood-brain barrier injury is an important pathological process that leads to a poor prognosis of cerebral ischemia reperfusion injury. However, due to the limited treatment methods and limitations of multiple factors, it is urgent to find new treatment methods to repair blood-brain barrier injury. OBJECTIVE: To review the relevant mechanisms of traditional Chinese medicine combined with bone marrow mesenchymal stem cells in regulating the blood-brain barrier after cerebral ischemia reperfusion injury, to further explore new ways to protect the blood-brain barrier and provide assistance for clinical treatment. METHODS: The keywords were “traditional Chinese medicine, bone marrow mesenchymal stem cells, blood-brain barrier, cerebral ischemia reperfusion injury” in Chinese and English. WanFang, CNKI, PubMed, and Web of Science databases from 2012 to 2022 were retrieved for articles regarding the related mechanism of the blood-brain barrier damage and the related mechanism of Chinese medicine combined with bone marrow mesenchymal stem cells in regulating the blood-brain barrier. The obsolete and unqualified articles were excluded and 97 articles were included for analysis and summary. RESULTS AND CONCLUSION: (1) The physiological structure of the blood-brain barrier and the pathological changes of the blood-brain barrier structure after cerebral ischemia reperfusion injury were combed. (2) This paper summarized the mechanism of traditional Chinese medicine combined with bone marrow mesenchymal stem cells in regulating the blood-brain barrier after cerebral ischemia reperfusion injury, including regulating the expression of tight junction protein, inhibiting the activity of aquaporin-4 and matrix metalloproteinase-9, promoting angiogenesis, inhibiting the release of inflammatory mediators, and regulating exosomes. (3) It is concluded that traditional Chinese medicine combined with bone marrow mesenchymal stem cells can improve the permeability of the damaged blood-brain barrier and provide assistance for clinical treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: With the aging of population, sarcopenia in type 2 diabetes mellitus has gradually emerged in front of people. Increasing physical activity is an important approach to prevent and treat type 2 diabetes mellitus and its related sarcopenia. However, current intervention plan, effect evaluation and mechanism of different physical activities in type 2 diabetes-related sarcopenia are still not detailed. OBJECTIVE: To analyze the intervention program, effect evaluation and mechanism of physical activity in type 2 diabetes-related sarcopenia, thereby providing theoretical basis and practical suggestions for physical activity to improve the disease. METHODS: Search terms included “Diabetes Mellitus; T2DM; Sarcopenia; Muscular Atrophy; Exercise; Training; physical activity” in English and Chinese. PubMed and CNKI were searched for relevant literature published from January 1986 to February 2022, including review papers, research papers and meta-analysis. Finally, 53 literatures were included for the review. RESULTS AND CONCLUSION: Appropriate increase in non-leisure physical activity (daily steps above 5 401 per day) can reduce the probability of sarcopenia and maintain physical exercise function in elderly type 2 diabetes patients. Increasing leisure physical activity can prevent the incidence of sarcopenia in elderly type 2 diabetes patients, and any regular physical exercise can be effective. Resistance exercise is significantly superior to aerobic exercise in the prevention and treatment of type 2 diabetes-related sarcopenia. A resistance exercise of moderate intensity and above (3 times a week, 70%-85% 1RM) can effectively increase muscle mass and strength performance in type 2 diabetes patients with sarcopenia, while aerobic exercise mainly delays skeletal muscle loss. Combining resistance exercise with aerobic exercise, nutritional intervention and health education can increase patient compliance and improve treatment efficacy. Resistance exercise mainly improves protein synthesis by activating IRS-PI3K-Akt, mTORC1, p70S6K and 4EBP1 signaling pathways, and improve muscle mass and functions by stimulating muscle satellite cell proliferation and differentiation. Aerobic exercise mainly delays muscle loss by inhibiting ubiquitin protein ligases Atrogin-1 and MuRF1 and skeletal muscle autophagy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Stem cells play an important role in liver regeneration and self-repair ability, which is of great significance for clinical diagnosis and treatment of liver diseases. OBJECTIVE: To summarize the current clinical trials and basic research in this field in and outside China, review the types of stem cells used to treat liver diseases in the past, and the treatment programs of various types of stem cells for various types of liver diseases, outline the clinical application prospects of various types of stem cells in the future application of liver diseases, and provide a research basis for the treatment of clinical liver diseases. METHODS: Using “stem cells, mesenchymal stem cells, hepatic stem cell, embryonic stem cell, induced pluripotent stem cell, hematopoietic stem cell, hepatopathy, non-alcoholic fatty liver disease, liver cirrhosis, liver failure, autoimmune hepatitis, hepatocellular carcinoma” as search words, the relevant articles in PubMed, Web of Science and Wiley e-journal databases were searched, and 71 articles were selected for review according to the inclusion criteria. RESULTS AND CONCLUSION: (1) Mesenchymal stem cells, liver stem cells, embryonic stem cells, induced pluripotent stem cells and hematopoietic stem cells are the main stem cells for the treatment of liver diseases. The characteristics, expression period and application of these stem cells in differentiation after liver injury are summarized in this paper. (2) In general, mesenchymal stem cells can repair liver through exosomes, matrix metalloproteinase and anti-inflammatory response. Liver stem cells can differentiate liver oval cells and small hepatocellular progenitor cells to form mature liver cells and promote liver injury repair. Induced pluripotent stem cells, embryonic stem cells and hematopoietic stem cells can transform into mature hepatocytes through rapid proliferation and differentiation. (3) The treatment of various liver diseases by stem cells is mainly achieved by inducing endogenous cell proliferation, immune regulation, inhibiting inflammation, promoting liver cell regeneration and repairing damaged tissues. (4) On the whole, at present, mesenchymal stem cells are relatively easy to obtain, have the broadest application prospects, and do not involve ethical issues. They are transforming from preclinical research to clinical research. Because mesenchymal stem cells can differentiate into various adult stem cells, they have the advantages of low immunogenicity, strong self-proliferation and differentiation ability. Especially for the treatment of immune hepatitis, liver cirrhosis and hepatocellular carcinoma and other liver diseases, mesenchymal stem cells have the most ideal effect. (5) Induced pluripotent stem cells are more effective in the treatment of end-stage liver disease because they can differentiate into specific somatic cells and hepatocytes without immune rejection. (6) However, stem cell transplantation can induce acute rejection, such as diarrhea, jaundice, and skin rashes. Poor histocompatibility between donors and recipients can easily lead to adverse reactions such as graft-versus-host reactions. After stem cell transplantation, the use of stem cells and its clinical safety assessment still need the support of more clinical trials and evidence-based medicine data. [ABSTRACT FROM AUTHOR]

BACKGROUND: Extracorporeal shock wave therapy as a new technology for burn treatment has been carried out for 16 years. It has achieved significant clinical effects in promoting burn wound healing and improving scar contracture, pruritus, pain, and skin erythema after burn. Up to date, there is still no standardized treatment guideline. Its molecular mechanism, action pathway and treatment parameters are worthy of more extensive and in-depth research. OBJECTIVE: To review the application and research progress of extracorporeal shock wave therapy in burn wound repair and scar treatment after burn. METHODS: Related literatures were searched in PubMed, Web of Science, CNKI, VIP and WanFang databases from their inception to February 2021, with the keywords of “extracorporeal shock wave therapy, shock wave, burns, burn scar, scar” in English and Chinese, respectively. A total of 132 papers were initially retrieved, and 59 papers that followed the inclusion criteria were used for analysis, summarization and review. RESULTS AND CONCLUSION: Extracorporeal shock wave therapy can promote burn wound healing through cell mechanotransduction, regulation of inflammatory response, promotion of angiogenesis, improvement of circulation and acceleration of cell proliferation and epithelialization. It can also soften and regulate the scar tissue, improve the symptoms either of itching or pain, and improve the appearance and function of the skin along with the scar. The therapeutic effect of extracorporeal shock wave on burn is embodied in both physical and biological effects. Cell mechanotransduction plays an important role in shock wave regulation of burn wound healing and hypertrophic scar development. The conduction of shock waves can cause the change of protein and gene expression and regulate the biochemical reaction in cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: In recent years, arthroscopic rotator cuff repair has become the “gold standard” of clinical treatment. However, the rate of postoperative retears after rotator cuff repair remains high, mainly because the original rotator cuff structure cannot be restored. Therefore, anatomical healing through surgery alone is not sufficient. With the development of tissue engineering, more and more scholars have found that it has great advantages for rotator cuff healing and can help stimulate the orderly regeneration of the tendon bone interface. As scholars continue to go deeper and deeper, various types of scaffolds, seed cells, and growth factors have emerged, which have great prospects. However, there are few related reviews at the domestic and international levels, which makes it inconvenient for clinicians and scholars in related fields to understand the recent status of research in general. OBJECTIVE: To provide a summary of recent research on scaffold materials, seed cells, and cytokines related to tissue engineering in the field of rotator cuff tendon bone healing, with the aim of shedding light on basic research and clinical progress in rotator cuff tendon bone healing. METHODS: The search terms “rotator cuff injury, tissue engineering” were searched in English and Chinese by computer in PubMed and CNKI databases. The literature retrieved within 10 years was screened to exclude irrelevant, low quality or duplicate literature, and other relevant literature was included manually. Eventually, 69 papers were included for result analysis. RESULTS AND CONCLUSION: Tissue engineering has a great potential in the field of regeneration of tendon-bone union sites. (1) Current scaffold materials can be broadly classified into three types (natural material scaffold, synthetic material scaffold, and composite material scaffold), each with its own advantages. However, composite scaffolds seem to be more promising as they can better mimic the original gradient structure of the tendon-bone interface. (2) The pigmentation of various types of stem cells and biologic factors has also been shown to stimulate the repair potential of damaged areas. Moreover, the selection of stem cell types and the study of the intrinsic molecular signaling pathways of various biologic factors still need to be further investigated, so as to clarify the time point and level of intervention of specific biologic factors and achieve the purpose of precisely inducing the regeneration of the original fourlayer structure. [ABSTRACT FROM AUTHOR]

BACKGROUND: The application of orthodontic force triggers autophagy in the periodontal tissue via diverse signaling pathways, augmenting or attenuating the activity of relevant cell types such as periodontal ligament cells, osteocytes, osteoclasts, and osteoblasts, thus facilitating the process of periodontal remodeling. OBJECTIVE: To review the research progress in orthodontic force mediated autophagy in periodontal tissue and its impact on orthodontic tooth movement. METHODS: The PubMed, Web of Science, China Biology Medicine disc and CNKI were searched for literature published from 2010 to 2023 to summarize the progress in orthodontics-related autophagy. And 76 papers were finally included in the analysis and discussion. RESULTS AND CONCLUSION: Orthodontic force can trigger a series of biochemical signal changes through periodontal mechanical receptors and aseptic inflammation they cause, leading to autophagy in periodontal tissue. Subsequently, autophagy generates corresponding feedback through cascaded amplified signaling pathways such as Phosphoinositide 3-kinase/protein kinase B, Hippo, and mitogen-activated protein kinase pathways, promoting periodontal tissue remodeling and ultimately achieving tooth movement and stability. Orthodontic force-induced autophagy can differentially regulate bone resorption on the tooth pressure side and bone formation on the tension side. Related targets have good prospects in the clinical application of orthodontic treatment. Orthodontics and autophagy have complex mechanisms. However, existing research has only focused on exploring the role of autophagy in orthodontic tooth movement. Further exploration is needed to investigate the mutual regulatory effects between autophagy and orthodontic tooth movement, as well as the interactions between upstream mechanical receptors and signaling pathways involved in related pathways. [ABSTRACT FROM AUTHOR]

BACKGROUND: Due to the anatomical and physiological characteristics of articular cartilage, its self-repair ability is limited, so how to repair large cartilage defects (diameter > 4 mm) has become one of the most attractive problems in the medical field. With the development of bio-materials and tissue engineering, the further development of scaffold technology, especially the hydrogel scaffold that simulates the microenvironment of extracellular matrix, provides a new therapeutic idea for the repair of cartilage injury OBJECTIVE: To summarize the properties of alginate, the preparation of alginate saline gel scaffold and the research progress in the repair of cartilage injury. METHODS: A computer-based search of Web of Science, PubMed, Wanfang and CNKI was performed for papers published from January 2016 to December 2020 with the key words of “alginate hydrogel; cartilage tissue engineering or chondro*, osteochondral, scaffold” in Chinese and English. According to the inclusion criteria, 60 articles were included for review. RESULTS AND CONCLUSION: (1) Alginate, as negatively charged natural hydrophilic polysaccharide, can endow traditional alginate saline gel with better mechanical properties, adhesion, biodegradability and biocompatibility by modification technology. (2) The modified alginate composite hydrogel scaffold is beneficial to maintain the normal morphology of seed cells, synthesize the corresponding extracellular matrix, promote the expression of cartilage-related genes, and show excellent chondrogenic ability. (3) It has been reported that alginate composite hydrogel scaffold can form cartilage tissue similar to the surrounding normal cartilage in animals and effectively repair the defect. (4) In summary, alginate composite hydrogel scaffold has a good ability to promote cartilage repair, which provides a new therapeutic idea for cartilage tissue engineering. However, this material needs to be supported by more perfect preclinical trial data to promote its clinical transformation process. [ABSTRACT FROM AUTHOR]

BACKGROUND: Polymethyl methacrylate bone cement has good stability, plasticity and space-occupying ability, and is currently the most commonly used antibiotic carrier in clinical practice. Topical application of antibiotic-loaded bone cements can prevent, delay or even eradicate infections in the skeletal muscular system, and is currently a common means of addressing the challenge of bone and joint infections. However, the addition of antibiotics can significantly affect the mechanical properties of polymethyl methacrylate bone cement and has the potential to cause adverse reactions. In addition, some scholars found that the antibiotic release rate of antibiotic-loaded bone cements is very low, and topical application of antibiotic-loaded bone cements does not effectively destroy bacteria and has the potential to cause bacterial resistance. Therefore, they questioned the effectiveness of antibiotic-loaded bone cements in controlling infections, and it has been widely debated. OBJECTIVE: To review the advantages and problems of antibiotic-loaded bone cements and to summarize the precautions for its clinical use. METHODS: The computerized searches were conducted on PubMed, Wanfang and CNKI databases using “antibiotic-loaded bone cements, polymethyl methacrylate, PMMA; bone cements, anti-bacterial agents, bone and bones, joints, elution, release, and mechanical” as the search terms in Chinese and English to search the relevant literature from January 1, 2017 to December 31, 2021. After excluding the literature that was not related to the article content, poorly innovative and duplicated, 68 papers were finally included for review. RESULTS AND CONCLUSION: Currently, antibiotic-loaded bone cements are one of the best options for the treatment of bone and joint infections. As research on antibiotic-loaded bone cements continues, many new methods have emerged to improve their antibiotic release, antimicrobial capacity and mechanical properties, and their use in clinical practice has also expanded. However, there are still many issues that have not been solved and further research is needed, such as the selection of antibiotics, dosage, and the optimal mixing method. In addition, the development and local application of modified materials and antibiotic substitutes that can be incorporated into polymethyl methacrylate bone cement are expected to solve the problem of bacterial resistance. It is believed that with the development of medicine, pharmacology and biomaterials science, polymethyl methacrylate bone cement will be more widely used in clinical practice. [ABSTRACT FROM AUTHOR]

BACKGROUND: Osteoarthritis is one of the most common degenerative diseases worldwide. Angiogenesis plays an important role in the occurrence and development of osteoarthritis, which is involved in the process of synovitis, cartilage destruction and degeneration, and osteophyte formation. However, the specific mechanism of angiogenesis-mediated osteoarthritis and the regulatory factors affecting angiogenesis have not been determined. OBJECTIVE: To review the pathogenesis of angiogenesis-mediated osteoarthritis, thereby providing reference for future basic research and clinical practice. METHODS: “Osteoarthritis, angiogenesis, angiogenesis inhibitors” were used as the key words in Chinese and English, respectively, for literature retrieval in PubMed and CNKI databases. Retrieval time was from 1980 to 2021. Documents regarding the role and influential factors of angiogenesis in osteoarthritis as well as angiogenesis inhibitors in the treatment of osteoarthritis were collected, including original articles, reviews, dissertations, academic papers, etc. According to the inclusion and exclusion criteria, a total of 74 articles were selected after primary screening and re-screening through reading title, abstract and full-text. RESULTS AND CONCLUSION: Angiogenesis promotes synovitis, cartilage destruction and degeneration, osteophyte formation, and joint pain, which is one of the important factors in the formation and exacerbation of osteoarthritis. The influential factors are angiogenic factors, inflammatory cytokines, interaction between nerves and vessels, exosomes, and non-coding RNAs. Therefore, inhibiting angiogenesis is a potent target for osteoarthritis therapy. Up to date, angiogenesis inhibitors are only confined to vitro experiments and animal models and their clinical application in osteoarthritis should be further discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND: With the improvement of the medical level and people’s higher requirements for the quality of life, the quality and requirements for cartilage repair in the clinic are getting more and more, but traditional repair methods cannot regenerate cartilage with good biological properties. OBJECTIVE: To review the research progress of autologous chondrocyte implantation in recent years, and to analyze its development process, basic science, indications, contraindications, surgical techniques, clinical efficacy and limitations, and look forward to the development trend of this field. METHODS: A computer-based online search of CNKI, PubMed, Web of Science databases, and Google Scholar was performed to retrieve papers published during 1990-2020 with the search terms “autologous chondrocyte implantation, cartilage defect, techniques, clinical effect, indications, contraindications, defect size, treatment after initial failure, return to sports, age, magnetic resonance imaging, limitation” in English and Chinese. The document types include treatise, reviews, case reports, and meta-analysis. A total of over 1 000 papers were retrieved, and 52 of them were included in the final analysis. RESULTS AND CONCLUSION: Autologous chondrocyte transplantation first appeared for the treatment of knee cartilage defects in the late 1980s. The first generation of autologous chondrocyte transplantation used periosteal patches to seal the cultured chondrocytes in the defect. Due to the proliferation of periosteal grafts, second-generation autologous chondrocyte transplantation used collagen membrane patches instead of periosteal patches. The third generation of autologous chondrocyte transplantation used three-dimensional culture technology to improve cell delivery, allowing minimally invasive implantation, which could regenerate normal cartilage structure with accelerating patient recovery. Autologous chondrocyte transplantation was an effective method to treat high tibia or femoral cartilage defects, but it must solve the problems consisting of coronal force line, ligament laxity, and meniscus injury. Because of the graft needing a long time to mature, patients needed a specific rehabilitation plan to return to the sport, which assisted the injured patients in restoring strength and neuromuscular coordination as much as possible before the graft was fully mature. [ABSTRACT FROM AUTHOR]

BACKGROUND: The repair of cranio-maxillofacial bone defects is still facing severe challenges, and the introduction of the concept of bone regeneration points out a new direction for this problem. Adipose-derived stem cells are easy to access and have strong osteogenic differentiation capacity, which are considered as ideal seed cells for cranio-maxillofacial bone regeneration.OBJECTIVE: To review the influencing factors of osteogenic differentiation of adipose-derived stem cells as well as the research progress in cranio-maxillofacial bone regeneration, thus providing ideas for further study on adipose-derived stem cells in promoting cranio-maxillofacial bone regeneration. METHODS: A computer-based online search of PubMed, Wanfang, and CNKI databases was performed to retrieve papers published from January 2013 to February 2020 with the search terms of “adipose-derived stem cells, cranio-maxillofacial, oral tissue regeneration, periodontal tissue regeneration, bone regeneration, bone defects, osteogenesis” in English and Chinese. Finally, 88 papers were included for summary. RESULTS AND CONCLUSION: Adipose-derived stem cells can be induced to differentiate to osteoblasts and are easy to acquire in large quantities. It has a strong ability of expansion in vitro and has a broad application prospect in the field of cranio-maxillofacial bone regeneration. miRNAs/microRNAs play a role in the osteogenic differentiation of adipose-derived stem cells. The osteogenic differentiation ability of adipose-derived stem cells can be improved by the means of co-culture with other cells, combined with platelet-rich plasma or modified titanium and gene technology. Compared with conventional extracorporeal scaffolds, adipose-derived stem cells combined with injectable scaffolds have greater potential in osteogenesis. Some progress has been made in repairing cranio-maxillofacial bone defects with adipose-derived stem cells, but there is still a lack of sufficient evidence in large-scale clinical trials. [ABSTRACT FROM AUTHOR]

BACKGROUND: Currently, it was confirmed that encapsulating islets with natural or synthetic biomaterials to form a barrier with the function of immune isolation can not only reduce the systematic use of immunosuppressive agents to a certain extent, but also make heterogenous islet transplantation possible. OBJECTIVE: To introduce the research progress of the biomaterials for islet transplantation, describe several models for encapsulating islet, and eventually discuss current research focus and prospects of islets encapsulating models. METHODS: The authors searched PubMed and Web of Science databases with the search terms “islet encapsulation, islet transplantation biomaterials, islet transplantation hydrogel” for relevant papers published. Initially, a total of 447 papers were retrieved, and 89 of them were included in the final analysis. RESULTS AND CONCLUSION: There are two main deficiencies in islet encapsulation for transplantation: one is the attack of immune rejection by the recipient; the other is the shortage of supply of oxygen and nutrient. Encapsulation of islet with a single material, synthetic or natural biomaterial, cannot address the two issues mentioned above. Herein, the biomaterial used for islet encapsulation must be modified. Current islet hydrogel models tend to combine synthetic biomaterials with natural biomaterials to take full advantage of the two kinds of biomaterials. In addition, immune-regulating drugs, angiogenic factors, or factors promoting the survival or function of islets can also be incorporated into the biomaterial. Besides, other cells can be involved to co-transplant with islets in the hydrogel. How to incorporate various strategies for addressing the above issues properly is the key of future research. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mesenchymal stem cell replacement therapy has always been regarded as one of effective methods for the treatment of fibrotic diseases. Its safety has been questioned. Exosomes are the paracrine products of mesenchymal stem cells with similar curative effects. This kind of cell-free therapy has now become the focus of researchers. OBJECTIVE: To summarize the role of mesenchymal stem cell-derived exosomes in the repair of lung, liver, heart and kidney fibrosis, and to look into the application of exosomes in the repair of radioactive salivary gland fibrosis. METHODS: PubMed database and CNKI database were retrieved with “exosomes, mesenchymal stem cells, tissue fibrosis, radiation salivary glands, repair” as keywords. Articles were filtered by a quick look at the article title and abstract. The articles that were not closely related to the topic were excluded. This paper finally selected 46 articles in intensive reading and writing. RESULTS AND CONCLUSION: Exosomes are mainly composed of lipids, proteins, nucleic acids, which have the functions of cell communication, anti-apoptosis, anti-inflammatory, and anti-fibrosis. The extraction methods are diverse and each has its advantages and disadvantages. Mesenchymal stem cell-derived exosomes play an important role in repairing fibrosis damage of the lung, liver, heart, and kidney. However, there are few studies on repairing tissue fibrosis caused by radioactive salivary gland damage, and it is worthy of in-depth study and exploration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Myeloid-derived suppressor cells are a heterogeneous group of cells derived from bone marrow, which can inhibit the function of T cells and exert immunosuppressive effect. Mesenchymal stem cells are pluripotent stem cells, which can inhibit innate and adaptive immune responses. Myeloid-derived suppressor cells and mesenchymal stem cells have many similarities in immunosuppressive function, which can be related to each other in tumor, inflammation and transplantation. OBJECTIVE: To summarize the mechanisms of action based on myeloid-derived suppressor cells and the effect of mesenchymal stem cells on the negative regulatory effect of immune response in myeloid-derived suppressor cells. METHODS: A computer search of the Web of Science Core Collection database was conducted with key words of “myeloid-derived suppressor cells”, “mesenchymal stem cells”, “stem cells”. Finally, 49 papers were included for review. RESULTS AND CONCLUSION: Myeloid-derived suppressor cells play an important immunosuppressive role in vivo by secreting arginase-1, inducible nitric oxide synthase, and indoleamine 2,3-dioxygenase. Myeloid-derived suppressor cells and mesenchymal stem cells interact through different mechanisms in the treatment of autoimmune diseases, organ transplantation, inflammatory infections, tumors and other diseases, causing tumor cells to evade immune surveillance and promoting further tumor progression. In non-tumor diseases, myeloid-derived suppressor cells play a certain benign regulatory role, weakening the body’s own immune response and improving clinical symptoms. [ABSTRACT FROM AUTHOR]

BACKGROUND: Articular cartilage degeneration is the main cause of osteoarthritis. Bone morphogenetic proteins play an important role in cartilage regeneration and repair. OBJECTIVE: To review the research progress of bone morphogenetic protein in the process of articular cartilage regeneration. METHODS: A computer-based online search of PubMed and Elsevier databases was performed using the keywords “bone morphogenetic proteins, BMPs, arthritis, osteoarthritis, OA, cartilage, chondrocyte” in English. A total of 272 papers were retrieved, 96 of which were included in final analysis. Another 27 papers related to concepts were also included. Therefore, 123 papers are finally included. RESULTS AND CONCLUSION: Bone morphogenetic proteins participate in many biological processes including cell proliferation, differentiation, migration, and apoptosis, and play an important role in the formation of bone and cartilage. Bone morphogenetic proteins participate in a variety of signaling pathway cascades by binding to different receptors, which can protect articular cartilage from cartilage destruction caused by inflammation and trauma. Bone morphogenetic proteins alone or in combination with other cytokines can repair cartilage defects improve degenerative lesions, and promote the differentiation and regeneration of articular chondrocytes. However, there are still some practical problems that need to be solved for the widespread use of bone morphogenetic proteins in cartilage regeneration, such as the safety of drug transporters, the lack of effective biological scaffold materials, the optimal dosage and time point of use of biological agents, and their toxic and side effects. Future research will focus on how to solve the above problems. The widespread application of bone morphogenetic proteins will open a new era for targeted treatment of cartilage damage and cartilage degenerative diseases represented by osteoarthritis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Interferon is a kind of cellular regulatory substance similar to polypeptide hormone, which has a wide range of biological activities, such as antivirus, anti-proliferation, antitumor and immunomodulatory functions. OBJECTIVE: To review the effect of interferon α-2b to inhibit scar formation in multiple organs, so as to provide a theoretical basis for clinical treatment of scar and fibrosis diseases. METHODS: A computer-based online search of WanFang, VIP, CNKI, PubMed, Web of Science and Elsevier Science Direct databases was performed to retrieve papers published during 1950-2020 with the search terms of “IFNα-2b, interferon α-2b, fibroblasts, scar, hypertrophic scar, keloid” in Chinese and English, respectively. A total of 42 papers were included for the final analysis. RESULTS AND CONCLUSION: Interferon α-2b can inhibit the occurrence and development of scar, reduce the production of extracellular matrix collagen, inhibit the proliferation of fibroblasts, and act on cytokines and gene targets related to fibrosis. Findings from this study provide a theoretical basis for the clinical application of interferon α-2b in the treatment of scar formation. [ABSTRACT FROM AUTHOR]

BACKGROUND: The healing of large segmental bone defects has been a clinical challenge, although several substances that promote osteogenesis have been identified. However, further studies are needed on the effects of inflammatory factors on bone healing, especially on the important factors affecting osteogenesis in the early stage of bone healing. OBJECTIVE: To summarize the relationship between interleukin-6 and bone metabolism, understand the mechanism of interleukin 6 in osteogenesis, and provide theoretical reference for new osteogenesis programs. METHODS: A search was conducted by the first author between July and August 2021 to retrieve relevant articles on PubMed database from January 1990 to July 2021 and CNKI database from January 1979 to July 2021. The English key words were “interleukin 6” or “bone metabolism” or “osteoblast” or “osteoclast” or “bone regeneration” or “mesenchymal stem cells” or “vascularization”. The Chinese key words were “interleukin 6” and “bone regeneration”, “interleukin 6” and “osteoblast”, “interleukin 6” and “osteoclast”, “interleukin 6” and “bone metabolism”. A total of 903 Chinese and English articles were obtained and 88 articles were included for review and analysis according to inclusion and exclusion criteria. RESULTS AND CONCLUSION: Interleukin 6, as a cytokine with a wide range of functions in vivo, also plays an important role in all stages of osteogenesis. (1) Interleukin 6 has been found to play an important role in various bone repair cells (such as mesenchymal stem cells, osteoblasts and osteoclasts) as well as in angiogenesis of bone defects. (2) Interleukin 6 interacts with a variety of osteogenic factors in vivo and exerts an effect in a vast network of bone repair. (3) Blood clots as an important factor can promote early bone healing; interleukin 6 can not only regulate the formation of blood clots, but also affect the structure of blood clots by regulating γ fibrin strips. The structure of blood clot has an important influence on the early stage of osteogenesis, so interleukin-6 can affect the early stage of bone healing by regulating the structure of blood clot. (4) In this paper, the specific mechanism of interleukin 6 affecting osteogenesis is reviewed, which is expected to further understand bone regeneration and healing, and provide new therapeutic strategies and protocols for osteogenesis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exosome is a membranous vesicle structure, which can be secreted by many types of cells and widely exists in blood, urine, cerebrospinal fluid, breast milk and other body fluids. It has the potential to mediate cell-to-cell communication and activate a variety of signal pathways. Studies have shown that mesenchymal stem cell-derived exocrine bodies can not only directly affect the function of brain parenchyma cells, but also have indirect neural repair effect, as a drug loading system can improve the therapeutic effect of traditional Chinese medicine. OBJECTIVE: To review the research progress on the mechanism of mesenchymal stem cell-derived exocrine bodies regulated by traditional Chinese medicine in the treatment of ischemic stroke. METHODS: The articles of Wanfang, CNKI, PubMed, Web of Science and other databases about mesenchymal stem cell-derived exocrine bodies regulated by traditional Chinese medicine in the treatment of ischemic stroke from 2009 to 2020 were searched, with “mesenchymal stem cells, exocrine, traditional Chinese medicine, ischemic stroke” as the key words in Chinese and English. The outdated and repetitive viewpoints were excluded, and the retrieved articles were analyzed and sorted out, and a total of 66 articles were included for analysis. RESULTS AND CONCLUSION: (1) The biological characteristics of exocrine derived from mesenchymal stem cells were combed. (2) Summarizing the mechanism of mesenchymal stem cell-derived exocrine in the treatment of ischemic stroke, including affecting blood-brain barrier permeability, angiogenesis, neurodifferentiation, nerve repair and immune inflammation. (3) Through the existing research, this paper summarizes the role of traditional Chinese medicine in regulating mesenchymal stem cell-derived exocrine in the treatment of ischemic stroke, including neuroprotection, angiogenesis, regulation of blood-brain barrier and so on. It may provide relevant reference for the clinical application of traditional Chinese medicine to regulate mesenchymal stem cell-derived exocrine in the treatment of ischemic stroke in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bone defect and bone healing have always been two major clinical problems. In recent years, targeted cytokines such as Interleukin-3 have been used to treat certain bone diseases, such as rheumatoid arthritis and multiple myeloma. OBJECTIVE: To summarize the relationship between interleukin-3 and bone metabolism, and to understand the mechanism of interleukin-3 in osteogenesis, so as to provide theoretical reference for new osteogenesis programs. METHODS: PubMed and CNKI were retrieved by the first author for relevant articles published January 1990 to March 2021 and from January 1979 to March 2021, respectively. The search terms used were “interleukin-3, bone metabolism, osteoblast, osteoclast, bone formation, mesenchymal stem cells, vascularization” in English and Chinese, respectively. A total of 896 articles detailing the mechanism of interleukin-3 and osteogenesis related metabolism were initially searched, and finally 56 eligible articles were included for further review and analysis. RESULTS AND CONCLUSION: Different from other cytokines, interleukin-3 has multi-lineage targeting potential and plays an important role in hematopoietic system. Studies have shown that interleukin-3 can directly interact with mesenchymal stem cells and promote their osteogenic differentiation. In addition, interleukin-3 has been shown to positively regulate the osteogenic differentiation of mesenchymal stem cells by stimulating the synthesis of bone morphogenetic protein-2. Although interleukin-3 has an effect on bone marrow stromal osteoblasts through inhibition of bone morphogenetic protein-2, no effects of interleukin-3 on the Runx2 and β-catenin pathways have been found. Bone absorption by osteoclasts can lead to bone loss. Early studies found that interleukin-3 could promote osteoclasts, while recent studies have shown that interleukin-3 could significantly inhibit c-Fms at mRNA and protein levels, and down-regulate the expressions of PU.1 and c-Fos, thus producing an inhibitory effect on osteoclasts. Therefore, the specific mechanism of interleukin-3 in osteoblasts and osteoclasts is thoroughly reviewed in this paper, with a view to providing references for future studies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Circular RNAs (circRNAs) were initially regarded as by-products of aberrant splicing. Present research on their mechanism has gradually penetrated to the molecular level. Many studies have shown that circRNAs participate in osteogenic differentiation through various ways and play a key role. OBJECTIVE: To discuss the research progress of circRNAs during osteogenic differentiation in human mesenchymal stem cells. METHODS: Using “circRNAs, human mesenchymal stem cells, osteogenic differentiation” as keywords in English and Chinese. PubMed, Web of Science, CNKI, and Wanfang were searched for relevant articles on circRNAs in human mesenchymal stem cells published from 1993 to 2020. Types of retrieved articles included reviews, research papers, and books. RESULTS AND CONCLUSION: CircRNAs play an important role in the osteogenesis of mesenchymal stem cells. These circRNAs have proven to be key targets for the diagnosis and treatment of bone diseases. However, the molecular mechanism of circRNA in osteogenic differentiation needs further research, and in vivo experiments are also needed to support existing conclusions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exosomes are closely related to insulin resistance diseases and play an important role in the diagnosis and treatment of insulin resistance diseases such as obesity and type 2 diabetes. In addition, exercise affects the biogenesis of the body fluid and the circulating exosomes, and mediates the role of intercellular communication. OBJECTIVE: To summarize the relationship between exosomes and insulin resistance diseases, and the role and mechanism of exercise-mediated exosomes in regulating insulin resistance related diseases. METHODS: The “extracellular vesicle, exosomes, insulin resistance, obesity, type 2 diabetes mellitus, exercise” were used as the key words. The literature related to PubMed and CNKI database from 1981 to 2020 was retrieved and 64 papers were selected according to inclusion and exclusion criteria. RESULTS AND CONCLUSION: Exosomes are closely related to the occurrence and development of insulin resistance diseases, and can be used as biomarkers for the diagnosis of obesity and type 2 diabetes, inhibiting the development of obesity and type 2 diabetes by down-regulating the expression of obesity-related inflammatory factors and improving insulin sensitivity. Mediated by aerobic exercise and resistance exercise, exosomes from different cell sources regulate the regulation of their miRNA and protein expression in patients with extensive insulin resistance. [ABSTRACT FROM AUTHOR]

BACKGROUND: As an extension of the "materialization" of image technology, three-dimensional (3D) printing is inseparable between the two. To meet the needs of clinical application, the combination of different principles of imaging technology and 3D printing technology makes it more possible in medical application. OBJECTIVE: To summarize the progress of medical application research of the combination of different imaging principles and 3D printing, and analyze its advantages and disadvantages. METHODS: The relevant articles from the databases of Web of Science, PubMed, CNKI, SinoMed and Wanfang were searched by computer. The subject headings "3D printed, Three-dimensional printing, Additional Manufacturing, Ultrasonography, Ultrasound, MRI, Magnetic Resonance Imaging, CT, Computed Tomography, PET/CT, SPECT/CT, Radiotherapy, Digital Subtraction, DSA" in English and "3D printing, ultrasound, MRI, radiotherapy, nuclear medicine" in Chinese were retrieved in the past five years, and finally 61 articles were included for review. RESULTS AND CONCLUSION: (1) This paper summarizes the medical application of 3D printing based on different types of image data, which is mainly divided into clinical application, equipment application and teaching application. The advantages and disadvantages of different image data sources are discussed and the difficulties in the combination of the two are summarized. (2) At present, the clinical application of medical 3D printing based on radiological imaging is wide, and the use is relatively mature. (3) With the in-depth application of 3D printing technology, non-ionized imaging methods such as MRI and ultrasound also show great potential in the application. [ABSTRACT FROM AUTHOR]

BACKGROUND: Insufficient amount of periodontal soft tissue always brings red-and-white aesthetic problems of natural teeth and restorations, leads to gingivitis and peri-implant inflammation. Cell scaffold complexes with different cell and material combinations can promote periodontal soft tissue regeneration, which is expected to replace autogenous grafts. OBJECTIVE: To review the research progress and breakthrough in the application of autologous or allogeneic fibroblasts, keratinocytes, and mesenchymal stem cells in periodontal soft tissue increment. METHODS: Literature retrieval was conducted in PubMed, CNKI, Wanfang, Sciencedirect, and Medline databases. The key words were “gingival recession, soft tissue augmentation, root coverage, subepithelial connective graft” in English and Chinese. Abstracts were read; conclusions were preliminarily screened; and studies and experiments unrelated to the topic of this paper were excluded. Finally, 61 articles were included for result analysis. RESULTS AND CONCLUSION: Mesenchymal stem cells show great potential in gingival papilla increment. Transplanting only fibroblasts or keratinocytes combined with collagen, chitosan, acellular dermal matrix and other scaffolds in soft tissue could not achieve the expected keratinized gingival increment. Although the combination of two kinds of cells and collagen matrix showed more optimistic results and the current scaffold materials had good plasticity and biocompatibility, co-culture of fibroblasts and keratinocytes is time-consuming and expensive, and the conformation of scaffold material is relatively single. How to solve these problems will be a long process. [ABSTRACT FROM AUTHOR]

BACKGROUND: Three-dimensional (3D) bio-printing provides a new way to solve the problem of organ donor scarcity in the field of tissue engineering and regenerative medicine. OBJECTIVE: To analyze the development trend of global 3D bio-printing technology, technology research and development hotspot, regional layout and cooperation trend, and main innovation subjects based on patent information. METHODS: Using Derwent Innovation as the data source, this paper conducts analysis on items of patent annual distribution, technology research and development hotspots, priority countries, and innovation subjects with tools of Derwent Data Analyzer and Excel. RESULTS AND CONCLUSION: (1) 3D bio-printing technology has entered a period of rapid development after 2013. 3D bio-printing equipment, technology and processes, biomedical materials, and polymer materials are the main hotspots. Medical model construction, medical implants, drug delivery, printing materials, 3D printing methods, craftsmanship and processes, medical devices and equipment are the core technologies in this field. The most prolific countries are China, the United States, and Korea. (2) The United States is the leader in core technology and product. Although China has a large number of patents, the occupancy of core technology patents is not high, and the quality and influence of patents need to be improved. (3) Foreign countries attach great importance to the layout of patents in the international market. China has fewer foreign patent applications and its global competition awareness is relatively lacking. (4) There are certain differences between countries in the concerned technical fields. Chinese research is focused on areas such as 3D printing equipment, systems, and tissue engineering scaffolds. From the perspective of innovation subject, foreign countries are dominated by enterprises and have a good industrial foundation, while universities are dominated and basic research is valued in China [ABSTRACT FROM AUTHOR]

BACKGROUND: Mesenchymal stem cell-based therapy is pursued aggressively with promising preclinical studies and higher future prospect in the treatment of nonhealing wounds. OBJECTIVE: To review the strategies for improving the efficacy of mesenchymal stem cells in the treatment of nonhealing wounds, which are expected to provide theoretical basis for clinical treatment of nonhealing wounds. METHODS: Wanfang, CNKI, PubMed and Web of Science were searched for articles about the application of mesenchymal stem cells in nonhealing wounds from March 2002 to March 2020. The key words were “mesenchymal stem cells, nonhealing wounds (nonhealing chronic wounds), wound repair, tissue regeneration” in Chinese and “mesenchymal stem cells, nonhealing chronic wound, wound repair, tissue regeneration” in English. After excluding outdated and repetitive viewpoints, the retrieved literature was sorted out and a total of 64 articles were included for analysis. RESULTS AND CONCLUSION: (1) The formation mechanism of nonhealing wounds was summarized. (2) The molecular mechanisms of mesenchymal stem cells in the treatment of nonhealing wounds were summarized, such as direct differentiation, paracrine, immunomodulatory, mobilization resident stem cells to participate in wound repair. (3) This paper summarized the improvement of the efficacy of mesenchymal stem cells in the treatment of nonhealing wounds, such as gene modification and pretreatment. (4) This study can provide a theoretical basis for improving the efficacy of mesenchymal stem cells in the treatment of nonhealing wounds. [ABSTRACT FROM AUTHOR]

BACKGROUND: The nervous system has a complex anatomical structure, where various related diseases can occur. The operation on the nerve system is difficult with high risk. Doctors are required to remove the diseased tissue completely, but not to damage important nerves, blood vessels and functional areas during the operation. Therefore, treatment methods and related auxiliary methods with accurate positioning and high surgical precision have been explored clinically. Three-dimensional (3D) printing is a rapid prototyping technology that has developed rapidly in recent years and has been widely used in biomedical industry. OBJECTIVE: To review the application status and prospect of 3D printing technology in neurosurgery. METHODS: The first author of this paper searched CNKI, WanFang, PubMed and Web of Science databases by using key words through computer. The deadline for publications was February 2020. A total of 385 related articles were retrieved. According to the inclusion and exclusion criteria, 49 articles were used for review after literature supplement. RESULTS AND CONCLUSION: In the field of neurosurgery, 3D printing customizes individualized implants that can be used to repair skull defects. The printed lesion model can be used for preoperative simulation of surgeries on deformity repair, cerebrovascular disease, skull base disease and spinal cord disease and provide the basis for individualized precision therapy. The model can also be used for neurosurgical education and preoperative education. Therefore, 3D printing technology has a broad development prospect in the field of neurosurgery. [ABSTRACT FROM AUTHOR]

BACKGROUND: With the development of life sciences and manufacturing science, the application of three-dimensional (3D) printing in the medical field has become increasingly widespread. OBJECTIVE: To analyze the level of application of 3D printing technology in the medical field, and to discuss the trends and constraints of 3D printing. METHODS: A computer-based retrieval of articles concerning 3D printing in the biomedical field was performed in CNKI, WanFang, Springerlink and PubMed databases. The key words were “3D printing; biomedical; tissue engineering” in Chinese or English and the retrieval time of papers was set as 2005-2017. RESULTS AND CONCLUSION: At present, the 3D printing technologies applied in the medical field mainly include stereolithography, selective laser sintering, fused deposition manufacturing, and 3D bioprinting. Different printing technologies have different application scopes. According to the biological properties of molding materials, the biological printing technology is divided into four levels of application: medical pre-operation model, in vivo implants, tissue engineering scaffolds, and cell structures. The printing procedures consist of pre-processing, printing processes, and post-processing. Existing biological manufacturing technologies are able to realize the precise positioning of components in the 3D space. Further investigation will focus on the balance of printing characteristics and biological characteristics of the materials and the fusion of multi-materials. [ABSTRACT FROM AUTHOR]