Hydrogels in Gene Delivery Techniques for Regenerative Medicine and Tissue Engineering.

Hydrogels are 3D networks swollen with water. They are biocompatible, strong, and moldable and are emerging as a promising biomedical material for regenerative medicine and tissue engineering to deliver therapeutic genes. The excellent natural extracellular matrix simulation properties of hydrogels enable them to be co-cultured with cells or enhance the expression of viral or non-viral vectors. Its biocompatibility, high strength, and degradation performance also make the action process of carriers in tissues more ideal, making it an ideal biomedical material. It has been shown that hydrogel-based gene delivery technologies have the potential to play therapy-relevant roles in organs such as bone, cartilage, nerve, skin, reproductive organs, and liver in animal experiments and preclinical trials. This paper reviews recent articles on hydrogels in gene delivery and explains the manufacture, applications, developmental timeline, limitations, and future directions of hydrogel-based gene delivery techniques.

Biomaterials derived from hard palate mucosa for tissue engineering and regenerative medicine.

Autologous materials have superior biosafety and are widely used in clinical practice. Due to its excellent trauma-healing ability, the hard palate mucosa (HPM) has become a hot spot for autologous donor area research. Multiple studies have conducted an in-depth analysis of the healing ability of the HPM at the cellular and molecular levels. In addition, the HPM has good maneuverability as a donor area for soft tissue grafts, and researchers have isolated various specific mesenchymal stem cells (MSCs) from HPM. Free soft tissue grafts obtained from the HPM have been widely used in the clinic and have played an essential role in dentistry, eyelid reconstruction, and the repair of other specific soft tissue defects. This article reviews the advantages of HPM as a donor area and its related mechanisms, classes of HPM-derived biomaterials, the current status of clinical applications, challenges, and future development directions.

Role and Mechanism of BMP4 in Regenerative Medicine and Tissue Engineering.

Bone morphogenetic protein 4 (BMP4) is emerging as a promising cytokine for regenerative medicine and tissue engineering. BMP4 has been shown to promote the regeneration of teeth, periodontal tissue, bone, cartilage, the thymus, hair, neurons, nucleus pulposus, and adipose tissue, as well as the formation of skeletal myotubes and vessels. BMP4 can also contribute to the formation of tissues in the heart, lung, and kidney. However, there are certain deficiencies, including the insufficiency of the mechanism of BMP4 in some fields and an appropriate carrier of BMP4 for clinical use. There has also been a lack of in vivo experiments and orthotopic transplantation studies in some fields. BMP4 has great distance from the clinical application. Therefore, there are many BMP4-related studies waiting to be explored. This review mainly discusses the effects, mechanisms, and applications of BMP4 in regenerative medicine and tissue engineering over the last 10 years in various domains and possible improvements. BMP4 has shown great potential in regenerative medicine and tissue engineering. The research of BMP4 has broad development space and great value.

Optogenetics in taste research: A decade of enlightenment.

The electrophysiological function of the tongue involves complicated activities in taste sense, producing the perceptions of salty, sweet, bitter, and sour. However, therapies and prevention of taste loss arising from dysfunction in electrophysiological activity require further fundamental research. Optogenetics has revolutionized neuroscience and brought the study of sensory system to a higher level in taste. The year 2022 marks a decade of developments of optogenetics in taste since this technology was adopted from neuroscience and applied to the taste research. This review summarizes a decade of advances that define near-term translation with optogenetic tools, and newly-discovered mechanisms with the applications of these tools. The main limitations and opportunities for optogenetics in taste research are also discussed.

Light-controlled scaffold- and serum-free hard palatal-derived mesenchymal stem cell aggregates for bone regeneration.

Cell aggregates that mimic in vivo cell-cell interactions are promising and powerful tools for tissue engineering. This study isolated a new, easily obtained, population of mesenchymal stem cells (MSCs) from rat hard palates named hard palatal-derived mesenchymal stem cells (PMSCs). The PMSCs were positive for CD90, CD44, and CD29 and negative for CD34, CD45, and CD146. They exhibited clonogenicity, self-renewal, migration, and multipotent differentiation capacities. Furthermore, this study fabricated scaffold-free 3D aggregates using light-controlled cell sheet technology and a serum-free method. PMSC aggregates were successfully constructed with good viability. Transplantation of the PMSC aggregates and the PMSC aggregate-implant complexes significantly enhanced bone formation and implant osseointegration in vivo, respectively. This new cell resource is easy to obtain and provides an alternative strategy for tissue engineering and regenerative medicine.

Genetically modified cell spheroids for tissue engineering and regenerative medicine.

Cell spheroids offer cell-to-cell interactions and show advantages in survival rate and paracrine effect to solve clinical and biomedical inquiries ranging from tissue engineering and regenerative medicine to disease pathophysiology. Therefore, cell spheroids are ideal vehicles for gene delivery. Genetically modified spheroids can enhance specific gene expression to promote tissue regeneration. Gene deliveries to cell spheroids are via viral vectors or non-viral vectors. Some new technologies like CRISPR/Cas9 also have been used in genetically modified methods to deliver exogenous gene to the host chromosome. It has been shown that genetically modified cell spheroids had the potential to differentiate into bone, cartilage, vascular, nerve, cardiomyocytes, skin, and skeletal muscle as well as organs like the liver to replace the diseased organ in the animal and pre-clinical trials. This article reviews the recent articles about genetically modified spheroid cells and explains the fabrication, applications, development timeline, limitations, and future directions of genetically modified cell spheroid.

Implant failure and associated risk factors of transcrestal sinus floor elevation: A retrospective study.

OBJECTIVES: This retrospective study aimed to evaluate early and late implant loss rates after transcrestal sinus floor elevation (TSFE) and to identify the risk factors related to these failures. MATERIAL AND METHODS: All patients treated with TSFE and simultaneous implant placement during October 2015 to March 2019 were evaluated for inclusion. A total of 802 patients with 976 implants met the inclusion criteria. Clinical and radiographic information was collected from medical records and image software. Univariate and multivariate Cox proportional hazards frailty regression models were performed to identify potential risk factors associated with early and late implant loss after TSFE. RESULTS: The 3-year cumulative implant survival rate was 96.9% (95% CI 95.8%-98.0%). Twelve implants in 12 patients were lost before or at the abutment connection, while 24 implants in 24 patients were lost after functional loading. The Cox frailty regression analyses indicated that two factors were correlated with early implant loss: TSFE with grafting materials, and operators with less clinical experience. As for late implant loss, RBH ≤6 mm, male sex, and certain implant brands were associated with a significantly increased failure rate. CONCLUSIONS: Transcrestal sinus floor elevation with simultaneous implant placement is a predictable treatment option in the atrophic maxilla. The presence of grafting materials and the lack of clinical experience of the surgeon were possibly associated with early implant loss, while low RBH, male sex, and certain implant brands tended to increase late implant loss.

High prevalence of vitamin D deficiency in Asia: A systematic review and meta-analysis.

Vitamin D deficiency is a worldwide health problem. However, the prevalence of vitamin D deficiency in Asian populations is unclear. The aims of our study were to investigate the prevalence of vitamin D deficiency and its association with different health outcomes in Asia. Searches for studies published from January 2009 to January 2021 were performed in the MEDLINE (via PubMed), EMBASE, and Web of Science databases. This study was registered in the PROSPERO database (CRD42021229841). In total, 472 studies with 746,564 subjects were included in the meta-analysis. The mean serum 25-hydroxyvitamin D (25[OH]D) concentration was 49.39 nmol/L; 20.93% of the participants had 25(OH)D levels <25 nmol/L, 22.82% had levels <30 nmol/L, 57.69% had levels <50 nmol/L, and 76.85% had levels <75 nmol/L. This review found that the prevalence of vitamin D deficiency in Asia is high. The factors significantly related to vitamin D deficiency were gender, age, altitude, region, and specific diseases (diabetes, cancer, fracture, systemic lupus erythematosus [SLE], fatty liver disease, osteopenia, thyroiditis, anemia, hepatitis, metabolic diseases, and dermatitis). These findings may serve as the foundation for more detailed public health strategies and policies on this issue.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1990850.

Maxillary sinus floor augmentation comparing removing versus retaining antral pseudocyst: A retrospective cohort study.

OBJECTIVES: To retrospectively compare multilevel volumetric changes in both hard and soft tissues between antral pseudocyst (AP) removal and retainment before maxillary sinus floor augmentation (MSFA) and immediate implant placement. MATERIAL AND METHODS: Twenty-six patients with 38 implants placed from 2016 to 2021 were included and divided according to a cohort design as follows: 13 removing the cyst (RC group) and 13 "leaving alone" the cyst (LC group). 3D radiographic parameters (primary outcome), 2D parameters and clinical records (secondary outcome) involving both hard and soft tissues were evaluated for four periods (T1: immediate postoperative, T2: 6-month, T3: 12-month, and T4: 2- to 5- year follow-up). Possible confounding factors, including sinus anatomical features and implant distribution, were also analyzed to eliminate their disturbance. RESULTS: The 3D volumetric change rate of bone grafts in the RC group (-9.32% ± 10.01%) from T2 to T3 was significantly lower than that in the LC group (-19.8% ± 10.59%) (p < .05). The change rate of apical bone height (ABH), endo-sinus bone gain (ESBG) and other 2D parameters were not significantly different between the two groups. 5.3% implants in RC group and 9.1% implants in LC group failed during follow-ups. 0% postoperative complications were observed in RC group. The Schneiderian membrane of RC group was significantly thinner than that of LC group at two measuring points in sinus. CONCLUSION: The present study demonstrated that compared to AP retainment, AP removal before MSFA and immediate implant placement can obtain higher bone graft volumetric stability and favorable prognosis.

Nanomaterial-based cell sheet technology for regenerative medicine and tissue engineering.

Nanomaterial-based cell sheet technology has been reported to be an effective method in regenerative medicine and tissue engineering. Here, we summarized several types of nanomaterials used to harvest cell sheets. Currently, the technology is divided into four categories according to the mechanisms: light-induced cell sheet technology, thermo-responsive cell sheet technology, magnetic-controlled cell sheet technology, and reactive oxygen species (ROS)-induced cell sheet technology. Furthermore, some studies have been conducted to show that nanomaterial-based cell sheets produce satisfying outcomes in the regeneration of bone, skeletal muscle, cardiac tissue, and tendon, as well as angiogenesis and osseointegration. Nevertheless, some shortcomings still exist, such as comprehensive preparation, unclear safety, and cell quality. Thus, future studies should aim to produce more types of nanomaterials to solve this problem.

Insights into the use of genetically modified decellularized biomaterials for tissue engineering and regenerative medicine.

Various modifications have been performed on biomaterials to improve their applications in tissue engineering and regenerative medicine. However, the challenges of immunogenicity and biocompatibility existed since the application of biomaterials. As a method to solve this problem, the decellularization process removes most living cells from biomaterials to minimize their immunogenicity; and preserves the native structures and compositions that favour cell growth and the subsequent construction of functional tissue. On the other hand, genetic modification of biomaterials aims to achieve specific functions (low immunogenicity, osteogenesis, etc.) or analyse the genetic mechanisms underlying some diseases (cardiac dysfunction, liver fibrosis, etc.). The combination of decellularization and gene modification is highly superior to biomaterials; thus, we must obtain a deeper understanding of these novel biomaterials. In this review, we summarize the fabrication approaches and current applications of genetically modified decellularized biomaterials and then discuss their disadvantages and corresponding future perspectives.

Genetically modified immunomodulatory cell-based biomaterials in tissue regeneration and engineering.

To date, the wide application of cell-based biomaterials in tissue engineering and regeneration is remarkably hampered by immune rejection. Reducing the immunogenicity of cell-based biomaterials has become the latest direction in biomaterial research. Recently, genetically modified cell-based biomaterials with immunomodulatory genes have become a feasible solution to the immunogenicity problem. In this review, recent advances and future challenges of genetically modified immunomodulatory cell-based biomaterials are elaborated, including fabrication approaches, mechanisms of common immunomodulatory genes, application and, more importantly, current preclinical and clinical advances. The fabrication approaches can be categorized into commonly used (e.g., virus transfection) and newly developed approaches. The immunomodulatory mechanisms of representative genes involve complicated cell signaling pathways and metabolic activities. Wide application in curing multiple end-term diseases and replacing lifelong immunosuppressive therapy in multiple cell and organ transplantation models is demonstrated. Most significantly, practices of genetically modified organ transplantation have been conducted on brain-dead human decedent and even on living patients after a series of experiments on nonhuman primates. Nevertheless, uncertain biosecurity, nonspecific effects and overlooked personalization of current genetically modified immunomodulatory cell-based biomaterials are shortcomings that remain to be overcome.

Genetically modified cell sheets in regenerative medicine and tissue engineering.

Genetically modified cell sheet technology is emerging as a promising biomedical tool to deliver therapeutic genes for regenerative medicine and tissue engineering. Virus-based gene transfection and non-viral gene transfection have been used to fabricate genetically modified cell sheets. Preclinical and clinical studies have shown various beneficial effects of genetically modified cell sheets in the regeneration of bone, periodontal tissue, cartilage and nerves, as well as the amelioration of dental implant osseointegration, myocardial infarction, skeletal muscle ischemia and kidney injury. Furthermore, this technology provides a potential treatment option for various hereditary diseases. However, the method has several limitations, such as safety concerns and difficulties in controlling transgene expression. Therefore, recent studies explored efficient and safe gene transfection methods, prolonged and controllable transgene expression and their potential application in personalized and precision medicine. This review summarizes various types of genetically modified cell sheets, preparation procedures, therapeutic applications and possible improvements.

Online dental teaching practices during the COVID-19 pandemic: a cross-sectional online survey from China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) emerged in China in December 2019. The COVID-19 pandemic hindered dental education, as school buildings were closed. Online dental teaching provided an alternative teaching tool for dental education. However, the efficiency of online dental teaching and student preferences for online dental teaching are unclear. AIM: To investigate the satisfaction with online dental teaching practices among undergraduate dental students and standardized resident physician training students during the COVID-19 pandemic in China. METHODS: A total of 104 undergraduate dental students and 57 standardized resident physician training students from Zhejiang University participated in the study. A 12-item survey was conducted. This investigation included the teaching methods received, frequency of classes, degree of satisfaction, preferred teaching method, whether to participate in a course regarding COVID-19 prevention, and the effects of teaching. The percentages were then calculated and evaluated for each item. RESULTS: A total of 161 students (104 undergraduate dental students and 57 standardized resident physician training students) participated in this survey. All students had online dental classes during the COVID-19 pandemic. Lecture-based learning (LBL), case-based learning (CBL), problem-based learning (PBL), team-based learning (TBL), and research-based learning (RBL) were selected as teaching methods. Students were more satisfied with LBL and CBL than PBL, RBL, and TBL. The majority of students had more than four classes per week. The most selected protective measures were hand washing, wearing masks, and wearing gloves. A total of 46.6% of students participated in courses on COVID-19. After training, the students consciously chose to wear face shields and protective clothing. CONCLUSIONS: Dental students accepted online dental learning during the COVID-19 pandemic. Students preferred LBL and CBL and were satisfied with the classes. Courses on COVID-19 helped students understand how to prevent COVID-19 transmission in the dental clinic.

1α,25-dihydroxyvitamin D3 promotes early osteogenic differentiation of PDLSCs and a 12-year follow-up case of early-onset vitamin D deficiency periodontitis.

Periodontitis is a chronic periodontal disease that contributes to tooth loss. In recent years, many animal studies have reported that vitamin D (VitD) deficiency results in chronic periodontitis. However, no studies have reported cases of early-onset periodontitis with VitD deficiency. This study reports a 5-year-old male patient with early-onset periodontitis, VitD deficiency and VitD receptor (VDR) mutation. The patient was treated with VitD and calcium, and received systematic periodontal treatment. During the 12-year treatment, the periodontal conditions of this patient were stable. Our in vitro study found that VitD could promote the expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (BMP2), bone gamma-carboxyglutamate protein (BGLAP), and VDR in the early osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Meanwhile, VitD could downregulate mRNA expression levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1ß (IL-1ß) and protein levels of IL-6 in the tumor necrosis factor-α (TNF-α) -induced inflammation of PDLSCs. Therefore, sufficient VitD supply can be a potential treatment for VitD deficiency induced early-onset periodontitis.

Recent advances in light-induced cell sheet technology.

Various stimuli have been applied to harvest complete cell sheets, including temperature, magnetic, pH, and electrical stimuli. Cell sheet technology is a convenient and efficient approach with beneficial effects for tissue regeneration and cell therapy. Lights of different wavelengths, such as ultraviolet (UV), visible light, and near infrared ray (NIR) light, were confirmed to aid in fabricating a cell sheet. Changes in the wettability, potential, or water content of the culturing surfaces that occur under light illumination induce conformational changes in the adhesive proteins or collagens, which then leads to cell sheet detachment. However, the current approaches face several limitations, as few standards for safe light illumination have been proposed to date, and require a careful control of the wavelength, power, and irradiation time. Future studies should aim at generating new materials for culturing and releasing cell sheets rapidly and effectively.