Tissue engineering and regenerative medicine最新文献

Background: Periodontitis and bone loss in the maxillofacial and dental areas pose considerable challenges for both functional and aesthetic outcomes. To date, implantable dental barrier membranes, designed to prevent epithelial migration into defects and create a favorable environment for targeted cells, have garnered significant interest from researchers. Consequently, a variety of materials and fabrication methods have been explored in extensive research on regenerative dental barrier membranes.

Methods: This review focuses on dental barrier membranes, summarizing the various biomaterials used in membrane manufacturing, fabrication methods, and state-of-the-art applications for dental tissue regeneration. Based on a discussion of the pros and cons of current membrane strategies, future research directions for improved membrane designs are proposed.

Results and conclusion: To endow dental membranes with various biological properties that accommodate different clinical situations, numerous biomaterials and manufacturing methods have been proposed. These approaches provide theoretical support and hold promise for advancements in dental tissue regeneration.

Background: Polylactic acid (PLA) is extensively used in the medical and cosmetic industries for skin regeneration and as a dermal filler due to its biocompatibility and biodegradability. However, the effectiveness of PLA as a cosmetic filler is limited by its slow degradation rate and poor cell attachment properties. Recent studies have focused on enhancing the performance of PLA by combining it with other materials. This study aimed to evaluate the performance of carboxymethyl cellulose (CMC), known for its high biocompatibility, in comparison with the widely used hyaluronic acid (HA).

Methods: Two types of PLA-based particles, HA-PLA and CMC-PLA were synthesized by combining PLA with HA and CMC, respectively. After characterizing the particles, we evaluated cell adhesion and viability using human dermal fibroblasts and analyzed gene and protein expression related to cell attachment and angiogenic paracrine factors.

Results: The CMC-PLA particles maintained a more uniform size distribution than the HA-PLA particles and exhibited superior cell adhesion properties. Cells attached on the CMC-PLA particles showed enhanced secretion of angiogenic paracrine factors, suggesting a potential improvement in therapeutic efficacy.

Conclusion: CMC-PLA particles demonstrated superior cell adhesion and secretion capabilities compared with HA-PLA particles, indicating their potential for application in skin regeneration and tissue recovery. Further research, including in vivo studies, is required to fully explore and validate the therapeutic potential of CMC-PLA particles.

Background: Exosomes and exosome mimetics are used as alternatives to cell therapy. They have shown potential in treating skin disorders by fortifying the skin barrier, mediating angiogenesis, and regulating the immune response while minimizing side effects. Currently, numerous studies have applied exosome therapy to treat atopic dermatitis (AD) caused by a weakened skin barrier and chronic inflammation. Research on exosomes and exosome mimetics represents a promising avenue for tissue regeneration, potentially paving the way for new therapeutic options. However, the efficacy of the therapy remains poorly understood. Also, the potential of exosome mimetics as alternatives to exosomes in skin therapy remains underexplored.

Methods: Here, we reviewed the pathological features and current therapies of AD. Next, we reviewed the application of exosomes and exosome mimetics in regenerative medicine. Finally, we highlighted the therapeutic effects of exosomes based on their cell source and assessed whether exosome mimetics are viable alternatives.

Results and conclusion: Exosome therapy may treat AD due to its skin regenerative properties, and exosome mimetics may offer an equally effective yet more efficient alternative. Research on exosomes and exosome mimetics represents a promising avenue for tissue regeneration, potentially paving the way for new therapeutic options.

Background: Despite advances in tissue engineering, current clinical reconstructive options for long segment tracheal defects are limited. In this study, a 3D printing based tubular tissue flap strategy was developed for long segment tracheal reconstruction.

Method: A stent-patterned airway scaffold with sufficient radial rigidity and longitudinal bending flexibility was designed and its mechanical behavior was analyzed using finite element analysis (FEA). The stent-patterned airway scaffolds with a removable central core to preserve an internal lumen were created by selective laser sintering (SLS) based 3D printing. The stent-patterned airway scaffold with the central core, filled with poly (ethylene glycol) diacrylate-dithiothreitol (PEGDA-DTT) hydrogel containing erythropoietin (EPO) to enhance vascularization, was then implanted into the latissimus dorsi muscle of a Yucatan minipig.

Results: A tubular tissue flap, with controlled luminal layer thickness was successfully created by removing the central core from the retrieved tissue flap containing the airway scaffold after 45 days of implantation in the Yucatan minipig model.

Conclusion: The current work validated the potential of the tubular tissue flap based on the 3D printing as a clinically viable tissue engineering strategy for long segment tracheal reconstruction.

Background: Peripheral nerve injuries are a major clinical challenge because of their complex nature and limited regenerative capacity. This study aimed to improve peripheral nerve regeneration using Wharton's jelly mesenchymal stem cells (WJ-MSCs) engineered to express brain-derived neurotrophic factor (BDNF) via a baculovirus (BV) vector. The cells were evaluated for efficacy when seeded into acellular nerve grafts (ANGs) in a rat sciatic nerve defect model.

Methods: WJ-MSCs were transfected with recombinant BV to upregulate BDNF expression. Conditioned medium (CM) from these cells was utilized to treat Schwann cells (SCs), and the impact on myelination-related markers, including KROX20, myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein β (S100β), and the activation of the mammalian target of rapamycin (mTOR)/ protein kinase B (AKT)/p38 signaling pathways were evaluated. In vivo, BDNF-expressing WJ-MSCs were seeded into ANGs and implanted into a rat sciatic nerve defect model. Functional recovery was evaluated via video gait analysis, isometric tetanic force measurement, muscle weight evaluation, ankle contracture angle measurement, and histological analysis using toluidine blue staining.

Results: BDNF expression was significantly upregulated in WJ-MSCs post-transfection. BDNF-MSC CM substantially promoted the expression of myelination markers in SCs and activated the mTOR/AKT/p38 signaling pathway. In the rat model, seeding of ANGs with BDNF-expressing WJ-MSCs resulted in improved functional outcomes, including enhanced toe-off angles, increased isometric tetanic force, greater muscle weight recovery, and a higher total number of myelinated axons compared with controls.

Conclusion: WJ-MSCs engineered to express BDNF significantly enhanced peripheral nerve regeneration when utilized in conjunction with ANGs. These findings indicate BDNF-expressing WJ-MSCs are a promising therapeutic approach for treating peripheral nerve injuries.

Background: Pancreatic islet transplantation holds great potential as a therapeutic approach for treating type 1 diabetes mellitus (T1D). However, large islets suffer from hypoxia due to the limited diffusion distance of oxygen, leading to cell loss. Therefore, smaller spheroids are needed for better transplantation outcomes. This study aims to develop a method for forming highly functional islet spheroids using glycol chitosan (GC) derivatives, such as N-acetylated glycol chitosan (AGC) and N-hexanoyl glycol chitosan (HGC).

Methods: Thermogelling polymers were produced by performing N-acylation of GC using the correspondingly carboxylic anhydrides. Islet spheroids were formed using a dual application with AGC-coated plates and HGC gelation. The AGC solution was applied to the plate for coating and evenly distributed using a 1 mL syringe. Then, the HGC encapsulated with islet single cells was cultured on top of it. Spheroid viability and functionality were evaluated using CCK-8 assay and glucose-stimulated insulin secretion assay.

Results: The aqueous solutions of AGC (4%, w/v) and HGC (36% hexanoylation) (2%, w/v) demonstrated a sol-gel transition temperature around 37 °C, suitable for the physiological environment. These polymers also showed no cytotoxicity to intact islets. Islet single cells were cultured on HGC gels with varying degrees of hexanoylation (DH) values, where higher DH values led to smaller and more uniform spheroids. The resulting spheroids formed on AGC-coated plates and HGC36 gelation were smaller and more uniform than those formed on untreated plates. These spheroids exhibited significantly improved glucose responsiveness, with superior insulin secretion.

Conclusion: The optimized method using AGC and HGC offers a more efficient way to produce smaller, uniform, and functional spheroids.

Background: Atherosclerosis often leads to ischemic heart disease and peripheral artery disease. Traditional revascularization technique such as bypass grafting using autologous vessels are commonly employed. However, limitations arise when patients lack suitable grafts due to underlying diseases or previous surgeries, prompting the need to substitute vessel grafts. Due to the high biocompatibility of decellularized products (grafts or scaffolds) prepared using supercritical carbon dioxide (ScCO₂), it has been widely applied in decellularization-related technologies in recent years. Therefore, this review article will comprehensively discuss the current developments in tissue vascular scaffolds applied to the treatment of cardiovascular diseases, with a particular focus on the application of supercritical carbon dioxide technology in this field and the challenges it faces.

Method: This review was compiled by searching relevant references on PubMed database (before June 2024) based on selected key words and specific terms.

Results: ScCO₂ is an effective and eco-friendly extraction agent widely used in industries like food, pharmaceuticals, and cosmetics. It has been applied in decellularization processes to obtain extracellular matrices (ECMs) from tissues. ScCO₂ technology has emerged as a promising method in cardiovascular disease treatment, particularly for developing tissue vascular scaffolds. ScCO₂ effectively removes cellular components while preserving the ECM, ensuring high biocompatibility and reduced immune response. It has been applied to decellularize tissues like heart valves and arteries, creating scaffolds that mimic natural ECM to support cell proliferation and tissue regeneration. Despite challenges such as solubility limitations and cost, ScCO₂ offers advantages like low toxicity and ease of use, making it a valuable tool in advancing regenerative medicine for cardiovascular applications.

Conclusion: ScCO₂ has the advantages of low cellular toxicity, cost-effectiveness, and ease of manipulation. These characteristics have the potential to lead to significant progress in cardiovascular research on tissue regeneration.

Background: Cell replacement therapy is the only treatment that restores or repairs the function of impaired tissues in neurodegenerative diseases, including vascular dementia (VaD); however, current VaD treatments focus on slowing or mitigating the underlying small vessel disease progression. We aimed to verify the improvement in neurocognition after administering human-induced pluripotent stem cell (hiPSC)-derived neural progenitor cells (NPCs) from in a VaD animal model.

Methods: After anesthesia, 10-12-week-old male C5BL/6 mice underwent sham or bilateral carotid artery stenosis (BCAS) surgeries. For BCAS, 0.18-mm micro-coils were wound around the bilateral common carotid arteries to induce chronic vascular insufficiency in the global brain. One day after surgery, the mice were administered phosphate buffer solution or NPC from hiPSCs via the tail vein for 15 d, and divided into sham (n = 6), VEH (n = 6), and NPC (n = 7) groups. Three months after the surgery, neurobehavioral tests including the Y-maze test (YMT), passive avoidance test (PAT), and novel object recognition test (NORT) were performed. Finally, mice brains were sectioned for evaluating microglia (Iba-1), astrocyte (GFAP) activation, and myelin (MBP) degeneration through immunohistochemistry (IHC).

Results: PAT latency (p = 0.01) and discrimination index in the NORT (p = 0.043) increased considerably in the NPC group than in the VEH group. However, alterations in YMT were not considerably higher in the NPC group than in the VEH group (p = 0.65). IHC tests revealed that the GFAP- and IBA-1-positive cell number was remarkably lower in the NPC group than in the VEH group (p < 0.05). Moreover, MBP density was higher in the NPC group.

Conclusion: hiPSC-derived NPCs have therapeutic potential in cerebral hypoperfusion VaD mice; it improves the working memory of VaD animals by diminishing inflammatory reactions and protecting them from demyelination.

Background: Mild head trauma often leads to long-term cognitive and neurological deficits. PLX3397, an inhibitor of colony-stimulating factor 1 receptor (CSF1R), offers promise as a therapeutic agent for traumatic brain injury (TBI) by targeting neuro-inflammation. Stem cell-based approaches are widely studied for neurological disorders. The objective of this study was to investigate therapeutic effect of intranasal administration of human neural crest-derived nasal turbinate stem cells (hNTSCs) on mild TBI in comparison with that of PLX3397.

Methods: We developed a model of mice with repetitive and mild TBI following a weight-drop once a day for 5 days. PLX3397 (50 mg/kg, p. o.) was administered for 21 days. Intranasal administration of hNTSCs (1 × 10⁶) was performed once.

Results: Iba1 + and GFAP + cells were increased in the cortex and hippocampus of TBI models. Iba1 + cells and GFAP + cells were remarkably decreased in PLX3397 or hNTSC-treated TBI models. Administration of PLX3397 attenuated the decrease in neurobehavioral activity. Similar effects were observed in a TBI model with a single dose of hNTSC.

Conclusion: Intranasal administration of hNTSCs had a microglia-depleting effect. Administered hNTSCs were found around the cortex and hippocampus of TBI brains. This investigation may provide a promising path for therapeutic initiatives for repetitive and mild TBI.