Bioengineering & Translational Medicine最新文献

Photodynamic therapy (PDT) using photosensitizer (PS)-embedded silicone membrane-covered self-expandable metallic stents (SEMSs) can function in palliative therapeutic option for malignant gastrointestinal tract obstruction. However, stent-related complications should be considered, and accurate delivery of light sources is technically difficult. Here, a Chlorin e6 (Ce6)-an embedded stent-based catheter is developed to improve its therapeutic efficacy and safety. PDT using Ce6-embedded stent successfully induced cell death of colorectal cancer cell line. PDT-treated liver tissues showed an increase in ablation depth in proportion to irradiation energy, and 600 J/cm² demonstrates an even and sufficient ablation depth. Endoluminal PDT using the Ce6-embedded stent-based catheter was technically successful in a rat colon model without procedure-related complications such as colonic perforation or stricture formation. The results in colonoscopy, colonography, and histological examination, along with statistical analysis, suggest that a novel PDT modality using a Ce6-embedded stent-based catheter was safely conducted and demonstrated apoptotic cell death at 12 h after PDT, and it gradually recovered from 2 to 4 weeks. Thus, the PDT using the Ce6-embedded stent-based catheter may represent a promising new approach for the treatment of malignant colorectal obstruction.

To review the theoretical basis and therapeutic effects of fecal microbiota transplantation (FMT) in various diseases in animal experiments and clinical studies, as well as the limitations and current standards of FMT application. PubMed and Web of Science databases were searched for articles published only in English between 1975 and 2023 on reliable results of animal experiments and clinical treatment of FMT. The properties of the gut microbiota and its interactions with the host metabolism are critical to human health, and microbiome disturbance is closely associated with human intestinal and extra-intestinal diseases. Therefore, therapeutic tools targeting on the modulation of gut microbiota have attracted increasing attention, among which FMT represents the most widely studied intervention strategy. This review gathered and summarized application of FMT in intestinal diseases, metabolic diseases, hypertension, cancer, nervous system diseases and arthritis, and elaborated the beneficial effects that can be achieved by altering the microbiota with FMT and the mechanisms of action. In addition, the potential risks and side effects of FMT approach are discussed, as well as current efforts to standardize the development of FMT. Through a systemic review of the outcome and mechanism of FMT in the treatment of intestinal diseases and extra-intestinal diseases, we aimed to provide a theoretical basis for the construction of an optimized FMT framework, so as to better exert its application prospects.

The advent of bioprinting has enabled the creation of precise three-dimensional (3D) cell cultures suitable for biomimetic in vitro models. In this study, we developed a novel protocol for 3D printing methacrylated collagen (ColMa, or PhotoCol®) combined with tendon stem/progenitor cells (hTSPCs) derived from human tendon explants. Although pure ColMa has not previously been proposed as a printable hydrogel, this paper outlines a robust and highly reproducible pipeline for bioprinting this material. Indeed, we successfully fabricated a 3D bioengineered scaffold and cultured it for 21 days under perfusion conditions with medium supplemented with growth/differentiation factor-5 (GDF-5). This bioprinting pipeline and the culture conditions created an exceptionally favorable 3D environment, enabling the cells to proliferate, exhibit tenogenic behaviors, and produce a new collagen type I matrix, thereby remodeling the surrounding environment. Indeed, over the 21-day culture period under perfusion condition, tenomodulin expression showed a significant upregulation on day 7, with a 2.3-fold increase, compared to days 14 and 21. Collagen type I gene expression was upregulated nearly 10-fold by day 14. This trend was further confirmed by western blot analysis, which revealed a statistically significant difference in tenomodulin expression between day 21 and both day 7 and day 14. For type I collagen, significant differences were observed between day 0 and day 21, as well as between day 0 and day 14, with a p-value of 0.01. These results indicate a progressive over-expression of type I collagen, reflecting cell differentiation towards a proper tenogenic phenotype. Cytokines, such as IL-8 and IL-6, levels peaked at 8566 and 7636 pg/mL, respectively, on day 7, before decreasing to 54 and 46 pg/mL by day 21. Overall, the data suggest that the novel ColMa bioprinting protocol effectively provided a conducive environment for the growth and proper differentiation of hTSPCs, showcasing its potential for studying cell behavior and tenogenic differentiation.

Minocycline is a commonly used drug for adjunctive therapy in periodontal disease. However, the current mainstream local medications primarily rely on intra-pocket administration, which, while avoiding the side effects of traditional systemic drugs, presents challenges such as inconvenience, discomfort, and the need for professional assistance, thus affecting patient compliance. Herein, we introduce a minocycline-loaded dissolvable microneedle (Mino-DMN) patch that allows for local and efficient delivery of minocycline to gingiva for the treatment of periodontitis. A two-step casting micro-molding process involving vacuum drying and freeze drying is employed to concentrate minocycline in the microneedle part and limit its diffusion into the patch backing. The resulting Mino-DMN patch features an array of minocycline-enriched gelatin MNs with a porous HA patch backing. The microneedles can penetrate into gingiva with enough mechanical strength and quickly release minocycline into the gingival tissue, ensuring prolonged local residence of the drug and minimizing its loss to saliva. In vivo experiments show Mino-DMN inhibits pro-inflammatory factors, promotes anti-inflammatory factors, and stimulates bone formation, surpassing topical application and comparable to the inconvenient and discomfort administration of Periocline®. This proposed Mino-DMN offers a simple, efficient, user-friendly strategy for the adjunctive treatment of periodontal disease.

We envision this work to assist researchers and medical device developers (beside other stakeholders) to better understand biomaterial-based medical device development and its approval process proposed by the new MDR and IVDR in the European Union, as more complex biomaterials emerge, with the MDR reflecting the progress in biomaterial discoveries. Additionally, insufficient international harmonization in regulatory laws and poor-quality data reporting contribute to the problem. This review describes the possible reasons for a slowing biomaterials translational trend observed over the past decades, focusing on the European Market, and suggests a feasible approach for biomaterials-based medical device translation into the clinic. Suitable solutions to upgrade biomaterial translation to the clinic have not yet been provided by the field: no additional hurdles should be imposed for researchers, clinicians, the medical device industry, and insurance companies, which all should collaborate on bringing innovative solutions to patients. The new MDR and IVDR represent a substantial advancement in ensuring patient safety and reflect a major step forward in healthcare. However, they should not constrain innovation in biomaterials-based medical device development. Incorporating reverse engineering from patient safety and a ‘safe by design’ (SbD) strategy early into medical device development might lead to a smoother and successful approval process. A solid R&D phase, with an emphasis on device safety and performance assessment, is fundamental to ensure an effective transition into the clinic. We offer an overview of the recently implemented regulations on medical devices and in vitro diagnostics across the EU, describing a shifting paradigm in the field of biomaterials discovery. As more complex biomaterials emerge, suitable regulations will be necessary to keep bringing safe and well-performing medical solutions to patients.

Mild traumatic brain injury (mTBI) is a common consequence of head injury but there are no recognized interventions to promote recovery of the brain. We previously showed that photobiomodulation (PBM) significantly reduced the number of apoptotic cells in adult rat hippocampal organotypic slice cultures. In this study, we first optimized PBM delivery parameters for use in mTBI, conducting cadaveric studies to calibrate 660 and 810 nm lasers for transcutaneous delivery of PBM to the cortical surface. We then used an in vivo weight drop mTBI model in adult rats and delivered daily optimized doses of 660, 810 nm, or combined 660/810 nm PBM. Functional recovery was assessed using novel object recognition (NOR) and beam balance tests, whilst histology and immunohistochemistry were used to assess the mTBI neuropathology. We found that PBM at 810, 660 nm, or 810/660 nm all significantly improved both NOR and beam balance performance, with 810 nm PBM having the greatest effects. Histology demonstrated no overt structural damage in the brain after mTBI, however, immunohistochemistry using brain sections showed significantly reduced activation of both CD11b⁺ microglia and glial fibrillary acidic protein (GFAP)⁺ astrocytes at 3 days post-injury. Significantly reduced cortical localization of the apoptosis marker, cleaved caspase-3, and modest reductions in extracellular matrix deposition after PBM treatment, limited to choroid plexus and periventricular areas were also observed. Our results demonstrate that 810 nm PBM optimally improved functional outcomes after mTBI, reduced markers associated with apoptosis and astrocyte/microglial activation, and thus may be useful as a potential regenerative therapy.

Congenital Heart Defects (CHDs) are the most common congenital anomalies, affecting between 4 and 75 per 1000 live births. Cardiovascular patches (CVPs) are frequently used as part of the surgical armamentarium to reconstruct cardiovascular structures to correct CHDs in pediatric patients. This review aims to evaluate the history of cardiovascular patches, currently available options, clinical applications, and important features of these patches. Performance and outcomes of different patch materials are assessed to provide reference points for clinicians. The target audience includes clinicians seeking data on clinical performance as they make choices between different patch products, as well as scientists and engineers working to develop patches or synthesize new patch materials.