Tissue Engineering. Part B, Reviews最新文献

Critical-sized bone defects (CSBDs) represent a significant clinical challenge, stimulating researchers to seek new methods for successful bone reconstruction. The aim of this systematic review is to assess whether bone marrow stem cells (BMSCs) combined with tissue-engineered scaffolds have demonstrated improved bone regeneration in the treatment of CSBD in large preclinical animal models. A search of electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) focused on in vivo large animal studies identified 10 articles according to the following inclusion criteria: (1) in vivo large animal models with segmental bone defects; (2) treatment with tissue-engineered scaffolds combined with BMSCs; (3) the presence of a control group; and (4) a minimum of a histological analysis outcome. Animal research: reporting of in Vivo Experiments guidelines were used for quality assessment, and Systematic Review Center for Laboratory animal Experimentation's risk of bias tool was used to define internal validity. The results demonstrated that tissue-engineered scaffolds, either from autografts or allografts, when combined with BMSCs provide improved bone mineralization and bone formation, including a critical role in the remodeling phase of bone healing. BMSC-seeded scaffolds showed improved biomechanical properties and microarchitecture properties of the regenerated bone when compared with untreated and scaffold-alone groups. This review highlights the efficacy of tissue engineering strategies for the repair of extensive bone defects in preclinical large-animal models. In particular, the use of mesenchymal stem cells, combined with bioscaffolds, seems to be a successful method in comparison to cell-free scaffolds.

With the recent developments in tissue engineering, scientists have attempted to establish seed cells from different sources, create cell sheets through various technologies, implant them on scaffolds with various spatial structures, or load scaffolds with cytokines. These research results are very optimistic, bringing hope to the treatment of patients with uterine infertility. In this article, we reviewed articles related to the treatment of uterine infertility from the aspects of experimental treatment strategy, seed cells, scaffold application, and repair criteria so as to provide a basis for future research.

Guided tissue regeneration (GTR) is an important surgical method for periodontal regeneration. By placing barrier membrane on the root surface of the tooth to guide the adhesion and proliferation of periodontal ligament cells, periodontal tissue regeneration can be achieved. This review intends to analyze the current limitations of GTR membranes and to propose possible solutions for developing new ones. Limitations of current GTR membranes include nonabsorbable membranes and absorbable synthetic polymer membranes exhibit weak biocompatibility; when applying to a large defect wound, the natural collagen membrane with fast degradation rate have limited mechanical strength, and the barrier function may not be maintained well. Although the degradation time can be prolonged after cross-linking, it may cause foreign body reaction and affect tissue integration; The clinical operation of current barrier membranes is inconvenient. In addition, most of the barrier membranes lack bioactivity and will not actively promote periodontal tissue regeneration. Possible solutions include using electrospinning (ELS) techniques, nanofiber scaffolds, or developing functional gradient membranes to improve their biocompatibility; adding Mg, Zn, and/or other metal alloys, or using 3D printing technology to improve their mechanical strength; increasing the concentration of nanoparticles or using directional arrangement of membrane fibers to control the fiber diameter and porosity of the membrane, which can improve their barrier function; mixing natural and synthetic polymers as well as other biomaterials with different degradation rates in proportion to change the degradation rate and maintain barrier function; to improve the convenience of clinical operation, barrier membranes that meets personalized adhesion to the wound defect can be manufactured; developing local controlled release drug delivery systems to improve their bioactivity. Impact statement This review provides an up-to-date summary of commonly commercial periodontal guided tissue regeneration membranes, and analyze their limitations in clinical use. Using studies published recently to explore possible solutions from several perspectives and to raise possible strategies in the future. Several strategies have tested in vivo/in vitro, which will guide the way to propel clinical translation, meeting clinical needs.

Organoids are widely considered to be ideal in vitro models that have been widely applied in many fields, including regenerative medicine, disease research and drug screening. It is distinguished from other three-dimensional in vitro culture model systems by self-organization and sustainability in long-term culture. The three core components of organoid culture are cells, exogenous factors, and culture matrix. Due to the complexity of bone tissue, and heterogeneity of osteogenic stem/progenitor cells, it is challenging to construct organoids for modeling skeletal systems. In this study, we examine current progress in the development of skeletal system organoid culture systems and analyze the current research status of skeletal stem cells, their microenvironmental factors, and various potential organoid culture matrix candidates to provide cues for future research trajectory in this field. Impact Statement The emergence of organoids has brought new opportunities for the development of many biomedical fields. The bone organoid field still has much room for exploration. This review discusses the characteristics distinguishing organoids from other three-dimensional model systems and examines current progress in the organoid production of skeletal systems. In addition, based on core elements of organoid cultures, three main problems that need to be solved in bone organoid generation are further analyzed. These include the heterogeneity of skeletal stem cells, their microenvironmental factors, and potential organoid culture matrix candidates. This information provides direction for the future research of bone organoids.

Articular cartilage defects significantly compromise the quality of life in the global population. Although many strategies are needed to repair articular cartilage, including microfracture, autologous osteochondral transplantation, and osteochondral allograft, the therapeutic effects remain suboptimal. In recent years, with the development of cartilage tissue engineering, scientists have continuously improved the formulations of therapeutic cells, biomaterial-based scaffolds, and biological factors, which have opened new avenues for better therapeutics of cartilage lesions. This review focuses on advances in cartilage tissue engineering, particularly in preclinical trials and clinical applications, prospects, and challenges.

Sharing the methods and results of clinical trials with full transparency is an ethical obligation for those involved in clinical research. In this regard, ClinicalTrials.gov requires reporting of results to the registry within 1 year of completion of the trial. However, a poor result reporting rate has been pointed out, with approximately half the trial results not been reported. It has been suggested that one of the reasons behind this could be the influence of sponsors who conduct the clinical trials. In the course of our previous trend analysis on regenerative medicine for stroke (STR) using ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) portal site as data sources, we suspected whether the results of gene and/or cell therapy trials are poorly reported. For this reason, a multivariate analysis using data from ClinicalTrials.gov was performed to identify the factors suppressing the result reporting rate, expanding our study to four different kinds of neurological diseases and regenerative medicine as a treatment modality when small-molecule compounds and biologics were set up as controls, in addition to the sponsor type factor. As a result, we found gene and/or cell therapy (therapeutic modality) in addition to STR (disease area), trials completed in 2005-2007, and clinical phases II and IV as independent factors that suppressed the rate of reporting results to ClinicalTrials.gov. On the other hand, big pharmaceutical companies were identified as a factor that increased the reporting result rate to ClinicalTrials.gov. When we applied result reporting publications through PubMed as an index, our study data revealed that the following factors were not identified as the cause for a decrease in the reporting result rate: STR (as disease area), trials completed between 2005 and 2007, and gene/cell therapy (as treatment modality). In this context, our findings indicate that gene/cell therapy has led to the suppression of the result reporting rate to ClinicalTrials.gov. This confirmed our initial suspicion of the low result reporting rate of gene/cell therapy trials. We believe that further studies are required to elucidate the factors affecting the result reporting rate from the perspective of disease area and treatment modality. Impact Statement Several studies have addressed the poor result reporting rate of clinical trials, which still remains an issue. Regenerative medicine holds great promise for the future and the process of its practical application is expected to be challenging. Although having a limited disease area and small sample size, to the best of our knowledge, this is the first study to point out insufficient result reporting of clinical trials of regenerative medicine from the perspective of treatment modality. This report highlights an issue for discussing the path toward its translation through an overview of various factors in comparison with conventional treatment modalities.

Peripheral nerve injury (PNI) is a common disease that has profound impact on the health of patients, but has poor prognosis. The gold standard for the treatment of peripheral nerve defects is autologous nerve grafting; notwithstanding, due to the extremely high requirement for surgeons and medical facilities, there is great interest in developing better treatment strategies for PNI. Low-intensity pulsed ultrasound (LIPUS) is a noninterventional stimulation method characterized by low-intensity pulsed waves. It has good therapeutic effect on fractures, inflammation, soft tissue regeneration, and nerve regulation, and can participate in PNI repair from multiple perspectives. This review concentrates on the effects and mechanisms of LIPUS in the repair of PNI from the perspective of LIPUS stimulation of neural cells and stem cells, modulation of neurotrophic factors, signaling pathways, proinflammatory cytokines, and nerve-related molecules. In addition, the effects of LIPUS on nerve conduits are reviewed, as nerve conduits are expected to be a successful alternative treatment for PNI with the development of tissue engineering. Overall, the application advantages and prospects of LIPUS in the repair of PNI are highlighted by summarizing the effects of LIPUS on seed cells, neurotrophic factors, and nerve conduits for neural tissue engineering.

Diabetes is a disease that plagues over 463 million people globally. Approximately 40 million of these patients have type 1 diabetes mellitus (T1DM), and the global incidence is increasing by up to 5% per year. T1DM is where the body's immune system attacks the pancreas, specifically the pancreatic beta cells, with antibodies to prevent insulin production. Although current treatments such as exogenous insulin injections have been successful, exorbitant insulin costs and meticulous administration present the need for alternative long-term solutions to glucose dysregulation caused by diabetes. Encapsulated islet transplantation (EIT) is a tissue-engineered solution to diabetes. Donor islets are encapsulated in a semipermeable hydrogel, allowing the diffusion of oxygen, glucose, and insulin but preventing leukocyte infiltration and antibody access to the transplanted cells. Although successful in small animal models, EIT is still far from commercial use owing to necessary long-term systemic immunosuppressants and consistent immune rejection. Most published research has focused on tailoring the characteristics of the capsule material to promote clinical viability. However, most studies have been limited in scope to biochemical changes. Current mechanobiology studies on the effect of substrate stiffness on the function of leukocytes, especially macrophages-primary foreign body response (FBR) orchestrators, show promise in tailoring a favorable response to tissue-engineered therapies such as EIT. In this review, we explore strategies to improve the clinical viability of EIT. A brief overview of the immune system, the FBR, and current biochemical approaches will be elucidated throughout this exploration. Furthermore, an argument for using substrate stiffness as a capsule design parameter to increase EIT efficacy and clinical viability will be posed.

Tendon injuries disrupt the transmission of forces from muscle to bone, leading to chronic pain, disability, and a large socioeconomic burden. Tendon injuries are prevalent; there are over 300,000 tendon repair procedures a year in the United States to address acute trauma or chronic tendinopathy. Successful restoration of function after tendon injury remains challenging clinically. Despite improvements in surgical and physical therapy techniques, the high complication rate of tendon repair procedures motivates the use of therapeutic interventions to augment healing. While many biological and tissue engineering approaches have attempted to promote scarless tendon healing, there is currently no standard clinical treatment to improve tendon healing. Moreover, the limited efficacy of systemic delivery of several promising therapeutic candidates highlights the need for tendon-specific drug delivery approaches to facilitate translation. This review article will synthesize the current state-of-the-art methods that have been used for tendon-targeted delivery through both systemic and local treatments, highlight emerging technologies used for tissue-specific drug delivery in other tissue systems, and outline future challenges and opportunities to enhance tendon healing through targeted drug delivery.