Tissue engineering and regenerative medicine最新文献

Background: Strontium ranelate (SR) is an effective bone regeneration drug; however, its low bioavailability and strong hydrophilicity cause a strong cytotoxicity, venous thrombosis, and allergic reactions when administered in its free form. This study aims to enhance the SR bioavailability by utilizing nanostructured lipid carriers (NLC) as a drug delivery system (DDS).

Methods: To improve the drug delivery efficiency and sustained release of the NLC, their surfaces were coated with chitosan oligosaccharide (COS), a natural polymer. The synthesis of COS-NLC was confirmed by measuring particle size and zeta potential, while surface morphology was evaluated using atomic force microscopy (AFM). SR loading efficiencies and release profiles were analyzed via reversed-phase high-performance liquid chromatography (RP-HPLC), and cytotoxicity was evaluated in mouse fibroblast L929 cells.

Results: Particle characterization indicated that the COS coating slightly increased the particle size (i.e., from 128.99 ± 2.77 to 131.46 ± 2.13 nm) and zeta potential (i.e., from - 13.94 ± 0.49 to - 6.58 ± 0.32 mV) of the NLC. The COS-NLC exhibited a high SR-loading efficiency of ~ 86.31 ± 3.28%. An in vitro release test demonstrated an improved sustained release tendency of SR from the COS-NLC compared to that from the uncoated NLC. In cytotoxicity assays using L929 cells, the COS coating reduced the cytotoxicity of the formulated DDS, and the SR-COS-NLC exhibited a 1.4-fold higher cell regeneration effect than SR alone.

Conclusion: These findings suggest that the developed COS-NLC serve as an effective and biocompatible DDS platform for the delivery of poorly bioavailable drugs.

Background: Branched polymers, including star, dendrimers, comb, and biomimetic polymers, are increasingly recognized for their potential in tissue engineering. Their unique architectures and functional properties contribute to enhanced mechanical strength, bioactivity, and adaptability of scaffolds and hydrogels.

Objective: This review explores the diverse applications of branched polymers in tissue engineering and regenerative medicine, emphasizing their role in mimicking the extracellular matrix (ECM) and modulating interactions at the material-bio interface. The structural features of branched polymers, including branching density and functional group distribution, are highlighted for their influence on drug delivery, mechanical properties, and cellular interactions.

Results: Branched polymers offer distinct advantages in tissue engineering: Star polymers: Provide tunable elasticity and facilitate long-range mechanical networking. Dendrimers: Enable precise functionalization for targeted drug delivery and cell signaling. Comb polymers: Enhance porosity and nutrient exchange in scaffolds. Biomimetic polymers: Mimic natural biological systems, promoting cellular adhesion, proliferation, and differentiation.

Conclusion: Branched polymers represent a versatile and promising platform for tissue engineering and regenerative medicine. Their ability to modulate biological interactions and adapt to diverse functional requirements underscores their potential to advance the field.

Background: Skin wound healing is a complex process requiring coordinated cellular and molecular interactions. Polynucleotides (PN) and hyaluronic acid (HA) have emerged as promising agents in regenerative medicine due to their ability to enhance cellular proliferation, angiogenesis, and extracellular matrix (ECM) remodeling. Combining PN and HA offers potential synergistic effects, accelerating wound repair.

Methods: PN and HA hydrogels were prepared and evaluated for viscosity and gel stability. Their effects on human dermal fibroblasts (HDF) and keratinocytes (HaCaT) were assessed using migration, proliferation assays, and gene expression analyses for vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and matrix metalloproteinase-10 (MMP-10). In vivo studies were conducted using a mouse wound model to observe wound closure and tissue regeneration over 14 days.

Results: The PN-HA mixture demonstrated superior mechanical stability compared to individual components. In vitro, PN-HA significantly enhanced HDF and HaCaT migration, proliferation, and upregulated VEGF, MMP-9, and MMP-10 expression. In vivo, PN-HA treatment accelerated wound closure, improved dermal thickness, and enhanced ECM remodeling, as evidenced by histological analyses.

Conclusion: The PN-HA combination synergistically accelerates wound healing by promoting angiogenesis, cellular migration, and ECM remodeling. These findings highlight its potential as an advanced wound dressing for acute and chronic wound management.

Background: Autotaxin (ATX), an ENPP2 enzyme, regulates lipid signaling by converting lysophosphatidylcholine to lysophosphatidic acid (LPA). Dysregulation of the ATX/LPA axis promotes inflammation and disease progression. BMP-22, a lipid ATX inhibitor, effectively reduces LPA production. However, its clinical utility is hampered by limitations in solubility and pharmacokinetics. To overcome these limitations, we developed BMP-22-incorporated lipid nanoparticles (LNP-BMP) to improve utility while maintaining ATX inhibition efficacy.

Methods: LNP-BMP was synthesized by incorporating DOTAP, DOPE, cholesterol, 18:0 PEG₂₀₀₀-PE, and together with BMP-22. The formulation of LNP-BMP was optimized and characterized by testing different molar ratios of BMP-22. The autophagy recovery and anti-inflammatory effects of LNP-BMP via ATX inhibition were evaluated in both macrophage cell line and mouse-derived primary macrophages.

Results: LNP-BMP was shown to retain its functionality as an ATX inhibitor and maintain the physical characteristics upon BMP-22 integration. Synthesized LNP-BMP exerted superior ability to inhibit ATX activity. When applied to M1-induced macrophages, LNP-BMP exhibited substantial anti-inflammatory effects and successfully restored autophagy activity.

Conclusion: The results demonstrate that LNP-BMP effectively inhibits ATX, achieving both anti-inflammatory effects and autophagy restoration, highlighting its potential as a standalone immunotherapeutic agent. Furthermore, the capacity to load therapeutic drugs into this formulation offers promising opportunities for further therapeutic strategies.

Background: Endoplasmin (ENPL), a heat shock protein 90 family member, promotes chondrogenic differentiation of stem cells by inhibiting ERK1/2 phosphorylation and inducing endoplasmic reticulum stress. However, its large size limits cellular uptake and therapeutic potential. To overcome this challenge, a cationic lipid nanoparticle (C_LNP) system was designed to deliver ENPL intracellularly, enhancing its effects on human tonsil-derived mesenchymal stem cells (hTMSCs).

Methods: ENPL-loaded cationic lipid nanoparticles (ENPL_C_LNP) were synthesized to facilitate intracellular ENPL delivery. The delivery efficiency and cytotoxicity were assessed in vitro using hTMSCs. Additionally, ENPL_C_LNPs were incorporated into a hyaluronic acid and chondroitin sulfate-based injectable hydrogel and tested for chondrogenic differentiation potential in a mouse subcutaneous model.

Results: ENPL_C_LNP achieved over 80% intracellular protein delivery efficiency with no cytotoxic effects. Co-cultured hTMSCs exhibited increased glycosaminoglycans (GAGs) and collagen expression over 21 days. In vivo, the hydrogel-embedded ENPL_C_LNP system enabled stable cartilage differentiation, evidenced by abundant cartilage-specific lacuna structures in regenerated tissue.

Conclusion: Combining ENPL_C_LNP with an injectable hydrogel scaffold supports chondrogenic differentiation and cartilage regeneration, offering a promising strategy for cartilage tissue engineering.

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: Curcumin, a well-known wound healing agent, faces clinical limitations due to its poor water solubility, rapid degradation, and short plasma half-life. To address these challenges, we developed a self-assembling peptide incorporating an antioxidant sequence (YGDEY), which is capable of not only delivering curcumin but also exhibiting additional bioactivity to enhance wound healing.

Methods: An antioxidant nanocarrier was developed via peptide self-assembly. To design an amphiphilic peptide for the nanocarrier assembly, antioxidant peptide sequence (YGDEY) as the hydrophilic segment and the hydrophobic block (WLWL) were incorporated to single peptide molecule. The peptide's self-assembly behavior and curcumin encapsulation were initially analyzed. Subsequent evaluations included cytocompatibility, cellular uptake, and antioxidant activity.

Results: Driven by strong interactions among their hydrophobic blocks (WLWL), the peptides formed well-defined nanostructures exhibiting high thermal stability. Furthermore, the encapsulation of curcumin within the micelle significantly improved its cellular penetration efficiency. When applied to fibroblast cells, the peptide-curcumin nanocomplexes exhibited synergistically enhanced antioxidant activity, which notably outperformed free curcumin and free peptide in scavenging reactive oxygen species.

Conclusion: These findings highlight the potential of the designed peptide-based nanocarrier to overcome intrinsic limitations of curcumin and enhance its therapeutic efficacy, providing a promising strategy for advanced wound healing applications.

Background: Vascular diseases, including atherosclerosis and thrombosis, are leading causes of morbidity and mortality worldwide, often resulting in vessel stenosis that impairs blood flow and leads to severe clinical outcomes. Traditional mechanical interventions, such as balloon angioplasty and bare-metal stents, provided initial solutions but were limited by restenosis and thrombosis. The advent of drug-eluting stents improved short-term outcomes by inhibiting vascular smooth muscle cell proliferation, however, they faced challenges including delayed reendothelialization and late-stage thrombosis.

Methods: This review highlights the progression from mechanical to biological interventions in treating vascular stenosis and underscores the need for integrated approaches that combine mechanical precision with regenerative therapies.

Results: To address long-term complications, bioresorbable stents were developed to provide temporary scaffolding that gradually dissolves, yet they still encounter challenges with mechanical integrity and optimal degradation rates. Consequently, emerging therapies now focus on biological approaches, such as gene therapy, extracellular vesicle treatments, and cell therapies, that aim to promote vascular repair at the cellular level. These strategies offer the potential for true vascular regeneration by enhancing endothelialization, modulating immune responses, and stimulating angiogenesis.

Conclusion: Integrating mechanical precision with regenerative biological therapies offers a promising future for treating vascular stenosis. A comprehensive approach combining these modalities could achieve sustainable vascular health.

Background: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.

Methods: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.

Results: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the Lucas-Kanade (LK) optical flow method, and provided better stability and accuracy in the results.

Conclusion: This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.

Background: Bone marrow aspiration concentrate (BMAC) has gained acceptance as a safe orthobiologic for treating osteoarthritis (OA), despite lacking robust supporting evidence. Although several publications have documented the use of BMAC in OA, evidence confirming its unequivocal efficacy remains limited.

Methods: This review aims to summarize the current clinical evidence regarding BMAC as a therapeutic for OA, while also presenting the author's perspective. Sixteen studies were reviewed, including ten randomized clinical trials (RCTs) and six cohort studies.

Results: From the review of existing literature, BMAC injections do not appear to significantly improve pain and function compared to conventional therapies such as hyaluronic acid and corticosteroids, although some studies report a longer duration of effectiveness. Furthermore, the evidence for structural improvement, which was the original rationale for cell therapy, is seldom reported.

Conclusion: In light of these findings, it is suggested that high-quality data from a large patient cohort is needed to determine the role of BMAC injections in OA treatment and address reimbursement issues. From the author's perspective, the introduction of a national registry system that provides valuable information on the cost-effectiveness of various orthopedic procedures may offer a solution.