Tissue-engineered Products Research Articles

Study of the Biodistribution of a Tissue-Engineered Product Based on Human Chondrocytes of Various Sources After Implantation into Balb/c Nude Mice

Study of the Biodistribution of a Tissue-Engineered Product Based on Human Chondrocytes of Various Sources After Implantation into Balb/c Nude Mice

Trials and tribulations of cell therapy for heart failure: an update on ongoing trials.

Heart failure (HF) remains a leading cause of mortality, responsible for 13% of all deaths worldwide. The prognosis for patients with HF is poor, with only a 50% survival rate within 5 years. A major challenge of ischaemia-driven HF is the loss of cardiomyocytes, compounded by the minimal regenerative capacity of the adult heart. To date, replacement of irreversibly damaged heart muscle can only be achieved by complete heart transplantation. In the past 20 years, cell therapy has emerged and evolved as a promising avenue for cardiac repair and regeneration. During this time, cell therapy for HF has encountered substantial barriers in both preclinical studies and clinical trials but the field continues to progress and evolve from lessons learned from such research. In this Review, we provide an overview of ongoing trials of cell-based and cell product-based therapies for the treatment of HF. Findings from these trials will facilitate the clinical translation of cardiac regenerative and reparative therapies not only by evaluating the safety and efficacy of specific cell-based therapeutics but also by establishing the feasibility of novel or underexplored treatment protocols such as repeated intravenous dosing, personalized patient selection based on pharmacogenomics, systemic versus intramural cell delivery, and epicardial engraftment of engineered tissue products.

Clinical translation of tissue-engineered oesophageal grafts: are patients ready for us?

PurposeWe sought to engage with expert patient/carers to understand attitudes towards use of tissue engineering (TE) for long-gap oesophageal atresia (OA).MethodsAn in-person engagement event for 70 patients/parents was held by the OA patient group, TOFS. Attitudes towards TE were assessed before and after a talk on use of TE oesophagi in a pre-clinical OA model. Perceptions were assessed using a 5-point Likert scale (median [range]) and compared using Mann–Whitney test.Results43 attendees responded; 56% parents/caregivers, 21% patients, 7% healthcare workers, 16% unreported. Most (85%) had some awareness of TE but for 15%, it was a new concept. Attendees were receptive to TE; 89% reported no concerns about growth of their/child(s) cells in a lab and 61% reported no concerns about using animal products. Perceptions of TE significantly improved after the presentation from 4 (2–5, n = 32) to 5 (3–5, n = 28) p < 0.0001, and 96% would like to be involved in focus groups on development of a TE product for use in OA.ConclusionInput from key stakeholders is essential to introduction of TE constructs clinically. The overall response to TE constructs was positive, and informs development of an OA-specific focus group to guide translation.

Can Whole-heart Tissue Engineering Products by Recellularization from Scaffolds Be Utilized on Humans in the Next Ten Years?

Diseases like organ failure lead to irreversible damage to our body, making organ transplantation the only treatment. However, though organ transplantation may be an effective treatment, problems of organ shortage and post-transplantation immune rejection still remain unresolved, making the development of alternative technologies vital. Organ regeneration is, therefore, a promising treatment as it aims to lower the chance of immune responses and may potentially solve the issue of organ shortage. An average procedure of organ regeneration has two steps: decellularization and recellularization. Decellularization techniques include physical, chemical, and enzymatic treatments, and these methods are often combined to maximize cell depletion, turning the organ into an extracellular matrix scaffold and minimizing the chances of immune rejection. Recellularization is the process of repopulating the scaffold with patient-specific cells, and is often completed through using perfusion systems by performing vascular perfusion and intramyocardial injections with the help of a bioreactor. This article explains the concept of whole-heart regeneration and assesses different methods of decellularization and recellularization to find the treatment with the highest efficacy and efficiency, while also conducting a case study on cultured epidermal autografts and primary research, in the form of a questionnaire, to look at the social acceptance of this technology, estimate the progress of whole-heart regeneration, and discuss its limitations.

ESOT Roadmap for Advanced Therapy Medicinal Products in Transplantation: Navigating Regulatory Challenges to Enhance Access and Care.

The field of organ transplantation is experiencing a transformative shift with the rise of Advanced Therapy Medicinal Products (ATMPs), which include gene therapies, somatic cell therapies, and tissue-engineered products. These therapies offer new, potentially curative treatments for longstanding medical challenges, impacting numerous patients. However, their adoption is hindered by complex regulatory frameworks, high production costs, and inconsistent access across Europe. The ESOT ATMP Task Force's position paper analyzes these challenges from research to clinical application, advocating for a coordinated strategy to position Europe as a leader in ATMP development. It proposes specific actions such as streamlining regulatory pathways to accelerate approvals, boosting funding for ATMP research, and creating specialized facilities for development and implementation. The paper also highlights the critical roles of patient engagement and real-world evidence in optimizing clinical and regulatory practices.

Effectiveness and Safety of Matrix-Associated Autologous Chondrocyte Implantation for the Treatment of Articular Cartilage Defects: A Real-World Data Analysis in Japan

Background: The effectiveness and safety of matrix-associated autologous chondrocyte implantation with an autologous periosteal flap (pMACI) remain unclear. The Japanese Ministry of Health, Labor, and Welfare requires postmarketing surveillance of all patients undergoing pMACI using the tissue-engineered product JACC. Purpose: To evaluate the effectiveness and safety of pMACI for large articular cartilage defects (≥4 cm2) in the knee joint using real-world data analysis. Study Design: Case series; Level of evidence, 4. Methods: Data were collected from patients who underwent pMACI between 2012 and 2019, with 2 years of follow-up. The primary outcomes were the Lysholm knee score and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6, 12, and 24 months. Adverse events were assessed by physical examination, magnetic resonance imaging, and/or arthroscopy. Results: Overall, 232 knees in 225 patients who presented with trauma (198 knees) or osteochondritis dissecans (34 knees) in the medial (132 knees) and lateral (44 knees) femoral condyle, patella (25 knees), trochlea (86 knees), and tibial plateau (4 knees) were included. The mean age of the patients was 40.9 ± 15.0 years, with mean cartilage defects of 5.6 ± 2.4 cm2 in size. Concomitant surgeries, such as osteotomy (50 knees), ligament reconstruction (27 knees), meniscal procedures (28 knees), osteochondral autograft transplantation (24 knees), and microfracture (14 knees), were performed in 113 (48.7%) knees. The minimal clinically important difference in the Lysholm knee score and KOOS Symptoms subscale was achieved in 79.7% and 63.5% of patients, respectively, and the Patient Acceptable Symptom State was achieved in 90.1% and 73.7%, respectively. Substantial clinical benefit was achieved in the KOOS Sports/Recreation and Quality of Life subscales at 39.6% and 37.8%, respectively. Knees that underwent concomitant microfracture had significantly worse KOOS values than the remainder of the cohort. Complications, including effusion (16.8%), graft delamination (14.7%), knee contracture (9.1%), graft hypertrophy (8.2%), and ossification (3.4%), were observed in 86 (37.1%) knees. Osteochondritis dissecans was significantly associated with graft hypertrophy and ossification, whereas concomitant surgery was significantly associated with delamination and contracture. Treatment failure required additional cartilage procedures in 11 (4.7%) knees. Conclusion: Treatment of large cartilage defects (≥4 cm2) with pMACI resulted in improved outcome scores in approximately 75% of patients. However, complications occurred in one-third of patients, and 4.7% required reoperation.

Assessment of Chondrogenic Potential of Human Dermal Fibroblasts with Various Protein Modifications

BACKGROUND: Hyaline cartilage is an avascular tissue that covers surface of large joints. This tissue, with a small number of cells and a high content of extracellular matrix proteins, has limited regenerative capacity. Recovery the articular cartilage remains a relevant and not yet fully resolved issue today. A promising approach is the use of biomedical products containing modified cells. AIM: To investigate the effects of different culture media on the chondrogenic modification of cells and to compare the results. METHODS: Human dermal fibroblasts and rabbit mesenchymal stem cells were modified using chondrogenic differentiation medium StemPro or recombinant TGF-β3 protein. Changes in the expression of genes responsible for chondrogenesis (Acan, Tgfβ3, Col2α1, Comp) were measured using the Real-Time PCR method -2ΔΔCt. RESULTS: It was shown that human dermal fibroblasts are capable of chondrogenic modification using protein media. This cell type is easily accessible for harvesting, does not require special conditions for cultivation, is easily scalable, and can be used for allogeneic transplantation. CONCLUSION: The obtained data can be used in the design of tissue engineering products for the regeneration of hyaline cartilage based on allogeneic dermal fibroblasts.

Recent advances in artificial intelligent strategies for tissue engineering and regenerative medicine.

Tissue engineering and regenerative medicine (TERM) aim to repair or replace damaged or lost tissues or organs due to accidents, diseases, or aging, by applying different sciences. For this purpose, an essential part of TERM is the designing, manufacturing, and evaluating of scaffolds, cells, tissues, and organs. Artificial intelligence (AI) or the intelligence of machines or software can be effective in all areas where computers play a role. The "artificial intelligence," "machine learning," "tissue engineering," "clinical evaluation," and "scaffold" keywords used for searching in various databases and articles published from 2000 to 2024 were evaluated. The combination of tissue engineering and AI has created a new generation of technological advancement in the biomedical industry. Experience in TERM has been refined using advanced design and manufacturing techniques. Advances in AI, particularly deep learning, offer an opportunity to improve scientific understanding and clinical outcomes in TERM. The findings of this research show the high potential of AI, machine learning, and robots in the selection, design, and fabrication of scaffolds, cells, tissues, or organs, and their analysis, characterization, and evaluation after their implantation. AI can be a tool to accelerate the introduction of tissue engineering products to the bedside. The capabilities of artificial intelligence (AI) can be used in different ways in all the different stages of TERM and not only solve the existing limitations, but also accelerate the processes, increase efficiency and precision, reduce costs, and complications after transplantation. ML predicts which technologies have the most efficient and easiest path to enter the market and clinic. The use of AI along with these imaging techniques can lead to the improvement of diagnostic information, the reduction of operator errors when reading images, and the improvement of image analysis (such as classification, localization, regression, and segmentation).

Immunophenotyping of a population of cultured human umbilical cord cells from Wharton's jelly

BACKGROUND: Against the background of many existing methods of defect replacement in post-traumatic injuries the methods of repair of damaged tissues based on methods using products of tissue engineering and cultures of artificially cultured human cells are becoming more and more widespread in medical practice. The literature reports weak immunogenic activity of human umbilical cord tissues, which makes these cells promising components of regenerative medicine products. Due to possible errors in explant selection and cell transformation in the process of cultivation, it is necessary to reliably determine the phenotype of cells obtained as a result of tissue explantation and their further cultivation. Thus, the specificity of obtaining multipotent mesenchymal cells from human umbilical cord Warton's stool tissues requires reliable identification of the type of the obtained cells. AIM: To obtain reliable features of mesenchymal stem cells in the cell population obtained from human umbilical cord stool tissue. MATERIAL AND METHODS: Methods of cell cultivation, flow cytofluorimetry, immunocytochemistry for determination of surface and intracellular markers of mesenchymal stem cells were used in the study. RESULTS: In the course of work on the identification of cells of the population obtained by culturing explants from human umbilical cord Wharton stool, the heterogeneity of the type of cells constituting the cell population was established. Most of them are mesenchymal stem cells carrying fluorescent markers CD45, CD73, CD34, CD29, CD90, CD44, CD105, which agrees with the immunophenotype of mesenchymal stem cells defined by the International Society for Cell Therapy. The ratio of the applied markers allows us to refer the population of cells obtained by direct explantation of Varton's gelatin tissue fragments to mesenchymal stem cells. Visual control confirmed the localisation of labelled antibodies on the surface of cultured cells. And also, it was shown that there were no vascular muscle cells in the obtained culture. CONCLUSION: As a result of experiments on identification of the cells obtained during explantation of Wharton's jelly tissue fragments and their further cultivation, their belonging to mesenchymal stem cells was established by immunofluorescence cytophotometry.

Supercooled preservation of cultured primary rat hepatocyte monolayers.

Supercooled preservation (SCP) is a technology that involves cooling a substance below its freezing point without initiating ice crystal formation. It is a promising alternative to prolong the preservation time of cells, tissues, engineered tissue products, and organs compared to the current practices of hypothermic storage. Two-dimensional (2D) engineered tissues are extensively used in in vitro research for drug screening and development and investigation of disease progression. Despite their widespread application, there is a lack of research on the SCP of 2D-engineered tissues. In this study, we presented the effects of SCP at -2 and -6°C on primary rat hepatocyte (PRH) monolayers for the first time and compared cell viability and functionality with cold storage (CS, + 4°C). We preserved PRH monolayers in two different commercially available solutions: Hypothermosol-FRS (HTS-FRS) and the University of Wisconsin (UW) with and without supplements (i.e., polyethylene glycol (PEG) and 3-O-Methyl-Α-D-Glucopyranose (3-OMG)). Our findings revealed that UW with and without supplements were inadequate for the short-term preservation of PRH monolayers for both SCP and CS with high viability, functionality, and monolayer integrity. The combination of supplements (PEG and 3-OMG) in the HTS-FRS solution outperformed the other groups and yielded the highest viability and functional capacity. Notably, PRH monolayers exhibited superior viability and functionality when stored at -2°C through SCP for up to 3days compared to CS. Overall, our results demonstrated that SCP is a feasible approach to improving the short-term preservation of PRH monolayers and enables readily available 2D-engineered tissues to advance in vitro research. Furthermore, our findings provide insights into preservation outcomes across various biological levels, from cells to tissues and organs, contributing to the advancement of bioengineering and biotechnology.

Possibilities of Bombyx mori (B. mori) biotechnological platform for regenerative medicine

Regenerative medicine aims at changing modern medicine practice by eliminating core reasons of diseases and disorders. Regenerative medicine includes gene therapy, cell therapy and products of tissue engineering that are destined for augmentation, regeneration or replacement of organs, tissues, genes and metabolic processes in the organism. Biomaterials are amongst key components of regenerative medicine on which successful strategies are based.The review of biotechnological methods implemented in the USP and DSP stages with the use of B. mori was made. The methods analysed are aimed at improving quality characteristics and obtaining new kinds of biomaterials to meet the needs of regenerative medicine and biomedicine. The diversity of biotechnological solutions that allow to gain a wide spectrum of biomaterials (incl. derivatives of cocoon shell such as fibroin, sericin and their composites; recombinant derivatives; antimicrobial peptides; modified transgenic silk fibres;transgenic fibres that contain growth factors and peptides; etc.) is a unique basis for the bioindustrial platform on the B. mori basis.

Influence of storage conditions on the viability of spheroids from human chondrocytes

BACKGROUND: The use of tissue-engineered products for treating hyaline cartilage injuries is currently a promising direction for regenerative medicine. The study of storage and transportation conditions of such preparations is essential in product development because it determines the viability and functional activity of the cellular component of the product. In addition, such work should be performed following the requirements of Russian legislation before using the developed drug product in clinical trials. AIM: To characterize the storage conditions for tissue-engineered preparations such as chondrospheres. METHODS: Chondrospheres were formed from human chondrocytes obtained from the biopsy material of the knee joint cartilage of patients diagnosed according to ICD-10 codes M15–M19. After the formation of chondrospheres, cell viability was examined using the metabolic dye PrestoBlue, and the expression of chondrogenic markers (SOX9, aggrecan, collagen type 1 and type 2) was preserved using real-time polymerase chain reaction under various transportation conditions, i.e., at different storage times, medium composition, and temperature. RESULTS: The analysis of the expression of chondrocyte markers confirmed that cells in chondrospheres retain a chondrocyte phenotype. In the cell viability study of tissue-engineered products under various conditions (temperature, solution, and time), the most favorable environment for storing the product was phosphate buffer saline and 0.9% sodium chloride solution (р 0.05). The metabolic activity of the cells that make up the tissue-engineered product was maintained when stored at +4 °C for up to 3 days (р 0.05). CONCLUSION: Isotonic solution and temperature regime +4 °C for not more than 2 days showed the preferable medium and conditions for storing and transporting the prototype cartilage implant as chondrospheres.

EFFECTS OF BIOPHYSICAL STIMULI ON OSTEOGENIC DIFFERENTIATION OF MESENCHYMAL STEM CELLS

Mesenchymal stem cells (MSCs) differentiate to cells that are part of tissues, such as bone and cartilage, both during ontogeny and for the repair/regeneration and renewal of tissues during postnatal life. Accordingly, MSCs can be a powerful tool for regenerative medicine and tissue engineering interventions in musculoskeletal deficiencies. MSCs found in the bone marrow and connective tissues are exposed to biochemical and biophysical factors that modulate their biological behavior. Given that biochemical factors have been widely studied, research on the effect of biophysical stimuli on the differentiation of MSCs is scarce. An overview of the impact of biophysical factors on MSCs osteogenic differentiation could shed light on some of the signals to consider when developing new cell therapies or tissue engineering products for the treatment of bone traumatic defects and diseases. The aim of this review is to provide an overview of the effect of biophysical stimuli on osteogenic differentiation. It focuses on reviewing what has been published on the effect of compression, tension, hydrostatic pressure, shear stress, electromagnetic fields, low-intensity ultrasound, and niche signaling – including topography and substrate stiffness, paracrine and juxtracrine regulation – on MSCs osteogenic differentiation. The knowledge gained from studying how MSCs respond to mechanical forces has the potential to drive the creation of more advanced treatments for conditions where bones are injured. These therapies could rely on either physical methods or a combination of physical and chemical approaches, offering new possibilities for improving bone health.

Cell-based medicinal products: a review of current research

INTRODUCTION. Cell therapies and tissue-engineered products are aimed at patients with severe conditions (genetic and neurodegenerative disorders, cancers, musculoskeletal injuries, burns, etc.) that lack alternative treatment options. Analysis of clinical efficacy data on cellbased medicinal products is important for understanding their translational potential in personalised medicine.AIM. This study aimed to review key trends in cell therapy, analyse data on approved cell therapies and tissue-engineered products, and assess challenges and prospects for their use.DISCUSSION. This article analyses data on the composition of cell therapies and tissue-engineered products, indications for their use, and the results of clinical studies. Cell-based medicinal products are derived from autologous or allogeneic mesenchymal and limbal stem cells, epithelial cells, chondrocytes, native or genetically engineered haematopoietic stem cells, genetically engineered lymphocytes (CAR-T, CAR-NK), etc. Medicinal products based on cell technologies have been approved in many countries, including the USA (approximately 30), the European Union (approximately 20), Japan (18), South Korea (15), etc. As of today, two cell therapies have been granted marketing authorisation in the Russian Federation. The first is based on CAR-T cells (a gene therapy product), and the other is based on chondrocytes (a cell-based medicinal product); the latter has been developed in Russia. The main advantages of cell therapy products include higher efficacy and fewer adverse drug reactions in comparison with standard treatment modalities. The main challenges of cell therapy include the risks of immune reactions and mutagenesis associated with lentiviral vectors or CRISPR/Cas9 technology, as well as limited efficacy of CAR-T and CAR-NK cells due to immunosuppressive properties of tumour microenvironment.CONCLUSIONS. In comparison with conventional treatment approaches, the use of cell therapies and tissue-engineered products can help effectively eliminate defects in various body tissues, avoid highly invasive surgical interventions, and reduce regeneration time. Thus, ensuring development of similar but at the same time more affordable Russian medicinal products can bring great benefits for the healthcare system of the Russian Federation.

Recent advancements in cartilage tissue engineering innovation and translation.

Articular cartilage was expected to be one of the first successfully engineered tissues, but today, cartilage repair products are few and they exhibit considerable limitations. For example, of the cell-based products that are available globally, only one is marketed for non-knee indications, none are indicated for severe osteoarthritis or rheumatoid arthritis, and only one is approved for marketing in the USA. However, advances in cartilage tissue engineering might now finally lead to the development of new cartilage repair products. To understand the potential in this field, it helps to consider the current landscape of tissue-engineered products for articular cartilage repair and particularly cell-based therapies. Advances relating to cell sources, bioactive stimuli and scaffold or scaffold-free approaches should now contribute to progress in therapeutic development. Engineering for an inflammatory environment is required because of the need for implants to withstand immune challenge within joints affected by osteoarthritis or rheumatoid arthritis. Bringing additional cartilage repair products to the market willrequire an understanding of the translational vector for their commercialization. Advances thus far can facilitate the future translation of engineered cartilage products to benefit the millions of patients who suffer from cartilage injuries and arthritides.

Current challenges in imaging the mechanical properties of tissue engineered grafts

The mechanical performance of tissue-engineered grafts is crucial in determining their functional properties, integration with native tissue and long-term repair outcome post-implantation. To date, most approaches for testing the mechanical properties of tissue-engineered grafts are non-sterile and invasive. There is an urgent need to develop novel sterile approaches for online monitoring mechanical properties of engineered tissues in order to ensure these engineered products meet the desired mechanical strength prior to implantation. In this paper, we overview various approaches for mechanical testing of engineered tissues, which span from traditional methods to medical imaging concepts in magnetic resonance elastography, ultrasound elastography, and optical coherence elastography. We focused on the applicability of these methods to the manufacturing of tissue-engineered products online, e.g., if such approach provides a sterile monitoring capacity and is capable of defining mechanical heterogeneity in engineered tissues throughout their growth in vitro in real-time. The review delves into various imaging modalities that employ distinct methods for inducing displacement within the sample, utilizing either strain-based or shear wave-based approaches. This displacement can be achieved through external stimulation or by harnessing ambient vibrations. Subsequently, the imaging process captures and visualizes the resultant displacement. We specifically highlight the advantages of novel non-invasive imaging methods such as ultrasound elastography and optical coherence elastography to assess the mechanical properties of engineered tissues in vitro, as well as their potential applications in cancer study, drug screening and the in vivo evaluation of the engineered tissues.

CT-Visible Microspheres Enable Whole-Body In Vivo Tracking of Injectable Tissue Engineering Scaffolds.

Targeted delivery and retention are essential requirements for implantable tissue-engineered products. Non-invasive imaging methods that can confirm location, retention, and biodistribution of transplanted cells attached to implanted tissue engineering scaffolds will be invaluable for the optimization and enhancement of regenerative therapies. To address this need, an injectable tissue engineering scaffold consisting of highly porous microspheres compatible with transplantation of cells is modified to contain the computed tomography (CT) contrast agent barium sulphate (BaSO4). The trackable microspheres show high x-ray absorption, with contrast permitting whole-body tracking. The microspheres are cellularized with GFP+ Luciferase+ mesenchymal stem cells and show in vitro biocompatibility. In vivo, cellularized BaSO4-loaded microspheres are delivered into the hindlimb of mice where they remain viable for 14 days. Co-registration of 3D-bioluminescent imagingand µCT reconstructions enable the assessment of scaffold material and cell co-localization. The trackable microspheres are also compatible with minimally-invasive delivery by ultrasound-guided transthoracic intramyocardial injections in rats. These findings suggest that BaSO4-loaded microspheres can be used as a novel tool for optimizing delivery techniques and tracking persistence and distribution of implanted scaffold materials. Additionally, the microspheres can be cellularized and have the potential to be developed into an injectable tissue-engineered combination product for cardiac regeneration.

Treatment of non-hypertrophic pseudoarthrosis of long bones with a Tissue Engineered Product loaded with autologous bone marrow-derived Mesenchymal Stromal Cells: Results from a phase IIa, prospective, randomized, parallel, pilot clinical trial comparing to iliac crest autograft

BackgroundAtrophic pseudoarthrosis is a serious complication with an incidence of 5–10 % of bone fractures located in the diaphysis of long bones. Standard treatments involve aggressive surgical procedures and re-interventions requiring the use of autografts from the iliac crest as a source of bone-forming biological activity (Standard of Care, SoC). In this context, regenerative ex vivo expanded osteogenic cell-based medicines could be of interest. Particularly, Mesenchymal Stromal Cells (MSC) offer new prospects to promote bone tissue repair in pseudoarthrosis by providing biological activity in an osteoconductive and osteoinductive environment. MethodsWe conducted a phase IIa, prospective, randomised, parallel, two-arms, open-label with blinded assessor pilot clinical trial to compare SoC vs. a tissue-engineered product (TEP), composed of autologous bone marrow (BM)-derived MSCs loaded onto allogeneic decellularised, lyophilised spongy bone cubes, in a cohort of 20 patients with non-hypertrophic pseudoarthrosis of long bones. Patients were followed up for 12 months. Radiological bone healing was evaluated by standard X-ray and computed tomography (CT) scanning. Quality of life was measured using the EUROQOL-5D questionnaire. ResultsTen patients were randomized to TEP and 10 to SoC with iliac crest autograft. Manufacturing of TEP was feasible and reproducibly achieved. TEP implantation in the bone defect was successful in all cases and none of the 36 adverse events (AE) reported were related to the treatment. Efficacy analyses were performed in the Full Analysis Set (FAS) population, which included 17 patients after 3 patients withdrew from the study. The degree of consolidation, estimated by measuring Hounsfield units (HU) on CT, showed no significant differences between the two treatment groups at 12 months post treatment (main efficacy variable) (p = 0.4835) or at 6 months. ConclusionsAlthough only a small number of patients were included in our study, it is notable that no significant differences were observed between the experimental treatment and SoC, thus suggesting TEP as an alternative where autograft is not available or contraindicated.

Development and Application of an Advanced Biomedical Material-Silk Sericin.

Sericin, a protein derived from silkworm cocoons, is considered a waste product derived from the silk industry for thousands of years due to a lack of understanding of its properties. However, in recent decades, a range of exciting properties of sericin are studied and uncovered, including cytocompatibility, low-immunogenicity, photo-luminescence, antioxidant properties, as well as cell-function regulating activities. These properties make sericin-based biomaterials promising candidates for biomedical applications. This review summarizes the properties and bioactivities of silk sericin and highlights the latest developments in sericin in tissue engineering and regenerative medicine. Furthermore, the extended application of sericin in developing flexible electronic devices and 3D bioprinting is also discussed. It is believed that sericin-based biomaterials have great potential of being developed into novel tissue engineering products and smart implantable devices for various medical applications toward improving clinical outcomes.

Comparative analysis of wound healing techniques in postoperative bladder cancer patients.

Bladder cancer is a highly prevalent malignancy that presents significant difficulties in the management of wounds following surgery. The present study investigated the critical necessity to optimize wound healing techniques in patients undergoing bladder cancer surgery by contrasting conventional approaches with advanced modalities in order to promote recovery and mitigate complications. The study assessed the efficacy of conventional and advanced wound healing methods in these patients, taking into account the complex interaction of patient-specific factors and surgical complexities. A cross-sectional analysis was performed on 120 patients who underwent bladder cancer surgery at the first affiliated hospital of Wenzhou Medical University. In addition to medical record evaluations and direct wound assessments, patient interviews were utilized to gather information regarding demographics, surgical specifics, wound healing methodologies and postoperative results. Survival analysis and logistic regression were utilized in statistical analysis, with potential confounding variables such as age, comorbidities and type of surgery being accounted for. Advanced wound healing techniques, such as negative pressure wound therapy, tissue-engineered products, bioactive dressings and platelet-rich plasma (PRP), exhibited distinct advantage in comparison with conventional suturing. The aforementioned techniques, especially PRP, resulted in expedited wound healing, decreased rates of complications (p < 0.05) and enhanced secondary outcomes, including curtailed hospital stays and decreased rates of readmissions. PRP therapy, in particular, demonstrated significant improvements with the faster mean time to wound healing of 9 ± 2 days and lower complication incidence of 2 (6.7%) (p < 0.05), indicating its superior efficacy. A subgroup analysis revealed that younger patients, males and those undergoing laparoscopic surgery exhibited superior outcomes (p < 0.05). The results were further supported by logistic regression and Cox proportional hazards models, which further indicated that sophisticated techniques, notably PRP therapy with a hazard ratio of 3.00 (2.00-4.50) and adjusted odds ratio of 0.20 (0.09-0.43), were effective in improving postoperative recovery. The research clarified the significant advantages that advanced wound healing techniques offered in postoperative care of patients diagnosed with bladder cancer. By customizing these methods to suit the unique requirements of individual patients and specific circumstances of surgical procedures, they can significantly enhance the recuperation process after surgery and set a new standard for patient care.