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Spinal cord injury (SCI) is a life-altering event, which often results in loss of sensory and motor function below the level of trauma. Biomaterial therapies have been widely investigated in SCI to promote directional regeneration but are often limited by their pre-constructed size and shape. Herein, the design parameters of microporous annealed particles (MAPs) are investigated with tubular geometries that conform to the injury and direct axons across the defect to support functional recovery. MAP tubes prepared from 20-, 40-, and 60-micron polyethylene glycol (PEG) beads are generated and implanted in a T9-10 murine hemisection model of SCI. Tubes attenuate glial and fibrotic scarring, increase innate immune cell density, and reduce inflammatory phenotypes in a bead size-dependent manner. Tubes composed of 60-micron beads increase the cell density of the chronic macrophage response, while neutrophil infiltration and phenotypes do not deviate from those seen in controls. At 8 weeks postinjury, implantation of tubes composed of 60-micron beads results in enhanced locomotor function, robust axonal ingrowth, and remyelination through both lumens and the inter-tube space. Collectively, these studies demonstrate the importance of bead size in MAP construction and highlight PEG tubes as a biomaterial therapy to promote regeneration and functional recovery in SCI.

Despite significant strides in medical treatments and surgical procedures for cardiovascular diseases, these conditions continue to be a major global health concern. The persistent need for innovative therapeutic approaches to mend damaged heart tissue highlights the complexity and urgency of this medical challenge. In recent years, stem cells have emerged as a promising tool for tissue regeneration, but challenges such as graft rejection and tumor formation have limited their clinical application. Exosomes, extracellular vesicles containing a diverse array of biomolecules, have garnered significant attention for their potential in regenerative medicine. The cardioprotective and reparative properties of mesenchymal stem cell-derived exosomes hold promise for the treatment of heart diseases. These exosomes can modulate various cellular processes, including angiogenesis, apoptosis, and inflammation, thereby enhancing cardiac function. Despite the growing interest, there remains a lack of comprehensive reviews synthesizing the molecular mechanisms, preclinical, and clinical evidence related to the specific role of MSC-derived exosomes in cardiac therapies. This review aims to fill that gap by exploring the potential of MSC-derived exosomes as a therapeutic strategy for cardiac diseases. This review explores the potential of mesenchymal stem cell-derived exosomes as a therapeutic strategy for cardiac diseases. We discuss the molecular mechanisms underlying their cardioprotective effects, summarize preclinical and clinical studies investigating their efficacy, and address the challenges and future perspectives of exosome-based therapies. The collective evidence suggests that MSC-derived exosomes hold promise as a novel and effective therapeutic approach for cardiac diseases. [ABSTRACT FROM AUTHOR]

Palmitoylethanolamide (PEA) is emerging as a promising therapeutic agent for neuropathic and other pain-related conditions. This naturally occurring fatty acid has drawn interest because of its ability to regulate pain and inflammation. Initially identified in food sources, PEA has been the subject of extensive research to elucidate its properties, efficacy, and clinical applications. PEA primarily exerts its effects through interaction with its primary receptor PPAR α, this interaction influences pain signalling pathways and neuroinflammatory processes by modulating the synthesis of pro-inflammatory cytokines, mast cell degranulation, microglial activation, and decrease of oxidative stress. PEA's interaction with endocannabinoid receptors decreases the inflammatory cytokine and chemokine production and thereby a descending pain sensation. The pharmacological and pharmacokinetic characteristics of PEA are examined in this paper, along with its potential for efficiency when used in in combination additional therapies in a variety of neurodegenerative disease models, including multiple sclerosis, Parkinson's disease, and Alzheimer's. Experimental evidence shows that PEA not only reduces pain and inflammation but also lowers the need for higher dosages of other drugs hence minimizing the risk of drug toxicity. The bioavailability of PEA has been enhanced by recent technological developments, which emphasize continuous research efforts to maximize PEA's therapeutic potential in pain treatment and associated medical sectors. [ABSTRACT FROM AUTHOR]

The aim of the present study was to survey the scientific literature for conclusive evidence about the capacity of ubiquinone to improve the healing process of soft and hard jaw tissue. A systematic review was conducted according to the PRISMA 2020 statement. An electronic search was undertaken in six databases and in the gray literature. Eight studies were identified, four of them in vitro, three in vivo, and one clinical. All articles demonstrated that ubiquinone accelerates the repair of soft tissue, whereas one study found little effect on the remodeling of bone tissue. Despite the possibility that ubiquinone application may be beneficial, the limited knowledge about the action of this coenzyme on oral tissue repair requires further preclinical studies before the development of human clinical trials. This systematic review provides valuable information about potential new medications that could help the healing of oral tissues, especially for oral and maxillofacial surgeons. [ABSTRACT FROM AUTHOR]

Background: Over the past 40 years since the discovery of regenerating family proteins (Reg proteins), numerous studies have highlighted their biological functions in promoting cell proliferation and resisting cell apoptosis, particularly in the regeneration and repair of pancreatic islets and exocrine glands. Successively, short peptides derived from Reg3δ and Reg3α have been employed in clinical trials, showing favorable therapeutic effects in patients with type I and type II diabetes. However, continued reports have been limited, presumably attributed to the potential side effects. Methods: This review summarizes extensive research on Reg proteins over the past decade, combined with our own related studies, proposing that Reg proteins exhibit dimorphic effects. Results: The activity of Reg proteins is not as simplistic as previously perceived but shows auto-immunogenicity depending on different pathophysiological microenvironments. The immunogenicity of Reg proteins could recruit immune cells leading to an anti-tumor effect. Such functional diversity is correlated with their structural characteristics: the N-terminal region contributes to autoantigenicity, while the C-type lectin fragment near the C-terminal determines the trophic action. It should be noted that B-cell masking antigens might also reside within the C-type lectin domain. Conclusions: Reg proteins have dual functional roles under various physiological and pathological conditions. These theoretical foundations facilitate the subsequent development of diagnostic reagents and therapeutic drugs targeting Reg proteins. [ABSTRACT FROM AUTHOR]

C‐X‐C motif chemokine ligand 12 (CXCL12; Stromal Cell‐Derived Factor 1 [SDF‐1]), most notably known for its role in embryogenesis and hematopoiesis, has been implicated in tumor pathophysiology and neovascularization. However, its cell‐specific role and mechanism of action have not been well characterized. Previous work by our group has demonstrated that hypoxia‐inducible factor (HIF)‐1 modulates downstream CXCL12 expression following ischemic tissue injury. By utilizing a conditional CXCL12 knockout murine model, we demonstrate that endothelial‐specific deletion of CXCL12 (eKO) modulates ischemic tissue survival, altering tissue repair and tumor progression without affecting embryogenesis and morphogenesis. Loss of endothelial‐specific CXCL12 disrupts critical endothelial–fibroblast crosstalk necessary for stromal growth and vascularization. Using murine parabiosis with novel transcriptomic technologies, we demonstrate that endothelial‐specific CXCL12 signaling results in downstream recruitment of non‐inflammatory circulating cells, defined by neovascularization modulating genes. These findings indicate an essential role for endothelial‐specific CXCL12 expression during the neovascular response in tissue injury and tumor progression. [ABSTRACT FROM AUTHOR]

Background: Treatment of peripheral nerve defects is a major concern in regenerative medicine. This study therefore aimed to explore the efficacy of a neural graft constructed using adipose mesenchymal stem cells (ADSC), acellular microtissues (MTs), and chitosan in the treatment of peripheral nerve defects. Methods: Stem cell therapy with acellular MTs provided a suitable microenvironment for axonal regeneration, and compensated for the lack of repair cells in the neural ducts of male 8-week-old Sprague Dawley rats. Results: In vitro, acellular MTs retained the intrinsic extracellular matrix and improved the narrow microstructure of acellular nerves, thereby enhancing cell functionality. In vivo neuroelectrophysiological studies, gait analysis, and sciatic nerve histology demonstrated the regenerative effects of active acellular MT. The Chitosan + Acellular-MT + ADSC group exhibited superior myelin sheath quality and improved neurological and motor function recovery. Conclusions: Active acellular-MTs precellularized with ADSC hold promise as a safe and effective clinical treatment method for peripheral nerve defects. [ABSTRACT FROM AUTHOR]

Stem cells, ideal for the tissue repair and regeneration, possess extraordinary capabilities of multidirectional differentiation and self‐renewal. However, the limited spontaneous differentiation potential makes it challenging to harness them for tissue repair without external intervention. Although conventional approaches using biomolecules, small organic molecules, and ions have shown specific and effective functions, they face challenges such as in vivo diffusion and degradation, poor internalization, and side effects on adjacent cells. Nanoengineered biomaterials offer a solution by solidifying and nanosizing these soluble regulating molecules and ions, facilitating their uptake by stem cells. Once inside lysosomes, these nanoparticles release their contents in a controlled "molecule or ion storm," efficiently altering the intracellular biological and chemical microenvironment to tune the differentiation of stem cells. This newly emerged approach for regulating stem cell fate has attracted much attention in recent years. This method has shown promising results and is poised to enhance clinical stem cell therapy. This review provides an overview of the design principles for nanoengineered biomaterials, discusses the categories and characteristics of nanoparticles, summarizes the application of nanoparticles in tissue repair and regeneration, and discusses the direction of nanoparticle‐enhanced stem cell therapy and prospects for its clinical application in regenerative medicine. [ABSTRACT FROM AUTHOR]

Efferocytosis, by phagocytosing and processing apoptotic cells in injured skin, directly influences the immune microenvironment. However, the comprehensive widespread inflammation and disrupted efferocytosis in injured skin cannot be effectively halted. Herein, "Grid Efferocytosis" strategy within injury site is proposed, which segments the inflammation regulatory into grid microdomains, and further rectifies intra‐grid immune microenvironment to accelerate tissue repair. GelMA/PLA/Laponite gridded fiber membranes (GPL) are custom‐designed via near‐field electrostatic printing, and then coated with HAMA‐PBA/EGCG hydrogel by photo‐crosslinking and dynamic borate bonding to form a composite fiber membrane (GPL‐E). Gridded modulation via GPL‐E confines the entire chaotic inflammatory microenvironment into controllable microinflammatory niches. Leveraging the hydrogel coating and boronic ester bond dissociation induced by microenvironmental glucose and reactive oxygen species, GPL‐E achieves dynamic anti‐glucose and anti‐oxidation within microdomains, reconstructing macrophage efferocytosis. Notably, the "grid efferocytosis" recruits repair cells into the grid by magnesium ion release triggered by Laponite exposure on fibers, and enhances endothelial cell vascularization by ≈2.5‐fold. In a mouse diabetic ischemic flap model, implantation of grid GPL‐E maintains flap‐to‐base fusion, attenuates inflammatory infiltration & spread, and improves blood perfusion for flap survival. This study demonstrates that "Grid Efferocytosis" rectifies the immune microenvironment, fostering tissue repair and regeneration. [ABSTRACT FROM AUTHOR]

The skin wound model in rats is a fundamental stage in preclinical trials, but there is a lack of standardization in these trials regarding the initial wound area, making analysis and comparison between studies difficult. Therefore, this study evaluates the healing progression of excisional skin lesions of varying diameters in Wistar rats, aiming to identify the optimal wound size for monitoring treatment effects on wound healing. Excisions of 0.8, 1.5, 2.0 and 3.0 cm in diameter were made on the back of the animals. Thirty animals were used per treatment and evaluated on days 3, 7, 10, 14 and 21 after surgery. The lesions were cleaned daily with saline solution until they were completely closed. The 0.8 cm group showed complete repair on D14, while in the other groups, the wounds persisted until day 21, with a reddened surface and no complete epidermal coverage, but with greater keratinization and presence of appendages in the 1.5 cm lesions. Therefore, as a standardization model for creating skin wounds, we suggest using 1.5 or 2.0 cm excisions, considering that 0.8 cm wounds close very early and 3.0 cm wounds, although behaving similarly to 2.0 cm wounds, are more invasive for the animals. The 1.5 cm model proved to be suitable for closure within 21 days. When evaluating a product intended to accelerate wound healing, 2.0 cm lesions are recommended to assess the effectiveness of the treatment. [ABSTRACT FROM AUTHOR]

Monocytes are crucial players in innate immunity. The human cytomegalovirus (CMV) infection has significant impacts on monocyte effector functions and gene expression. CMV, a β-herpesvirus, disrupts key monocyte roles, including phagocytosis, antigen presentation, cytokine production, and migration, impairing their ability to combat pathogens and activate adaptive immune responses. CMV modulates monocyte gene expression, decreasing their capacity for antigen presentation and phagocytosis while increasing pro-inflammatory cytokine production, which can contribute to tissue damage and chronic inflammation. CMV also alters monocyte migration to sites of infection while promoting trans-endothelial migration, thus aiding viral dissemination. Additionally, the virus affects reactive oxygen species (ROS) production, thereby contributing to end-organ disease associated with CMV infection. Overall, these changes enhance viral persistence during acute infection and facilitate immune evasion during latency. We highlight the clinical significance of these disruptions, particularly in immunocompromised patients such as transplant recipients, where the modulation of monocyte function by CMV exacerbates risks for infection, inflammation, and graft rejection. An understanding of these mechanisms will inform therapeutic strategies to mitigate CMV-related complications in vulnerable populations. [ABSTRACT FROM AUTHOR]

Exosomes (exos), nanoscale extracellular vesicles, play a critical role in tissue development and function. Stem cell-derived exos, containing various tissue repair components, show promise as natural therapeutic agents in disease treatment and regenerative medicine. However, challenges persist in their application, particularly in targeted delivery and controlled release, which are crucial for enhancing their biological efficacy. The integration of medical devices may provide a superior platform for improving drug bioavailability. Consequently, the combination products of stem cell-derived exos and medical devices present novel opportunities for expanding the therapeutic potential of exosomes. This review offers a comprehensive overview of the current research frontier in stem cell-derived exos combined with medical devices and discusses the prospective challenges and future prospects in this field. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a joint disease that causes pain, stiffness, and reduced joint function because the protective cushioning inside the joints, called cartilage, gradually wears away. This condition is caused by various factors and complex processes in the joint's environment, involving different types of cells producing factors that can either maintain the joint health or contribute to osteoarthritis. This study aimed to understand the factors influencing both healthy and diseased joints in DDD strategies for the in vitro preconditioning of MSCs. An electronic search in the PubMed, Scopus, and Web of Science databases was carried out using the terms (cartilage OR chondr*) AND (repair OR regeneration OR healing) AND (niche OR microenvironment)) AND ("growth factor" OR GF OR cytokine). Researchers used various methods, including macroscopic examinations, histology, immunohistochemistry, and microCT. Molecules associated with joint inflammation were identified, like macrophage markers, MMP-13, TNF, apoptotic markers, and interleukins. Chondrogenesis-related factors such as aggrecan GAG, collagen type II, and TGF beta family were also identified. This study suggests that balancing certain molecules and ensuring the survival of joint chondrocytes could be crucial in improving the condition of osteoarthritic joints, emphasizing the importance of chondrocyte survival and activity. Future preconditioning methods for MSC- and EV-based therapies can find suitable strategies in the described microenvironments to explore co-culture systems and soluble or extracellular matrix factors. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the photobiomodulation effects on the receptor area for full‐thickness skin graft integration. Methods: Thirty‐Six Wistar rats were divided: red laser (660 nm), infrared laser (808 nm), and control. A skin segment with 5 × 3 cm was removed. In the control, the skin was reallocated after a 180° rotation. For the 660 nm and 808 nm, the receptor area was first irradiated, and then the skin was reallocated the same as the control. Euthanasia occurred on the third and seventh days after the procedure, and macroscopical of necrosis and histological analysis were realized. Results: The 660 nm reached the lowest necrosis percentage on Day 7. In the 808 nm, necrosis increased between the two periods. Similar morphological findings were observed for the control and 660 nm; however, the 808 nm showed significant alterations in fibrosis and inflammatory infiltrate. Conclusion: The infrared wavelength showed inferior performance on skin graft integration compared to the control and the red wavelength. [ABSTRACT FROM AUTHOR]

Zhikang Zhu,1,* Xinge Zhang,1,* Xuran Lin,1 Yuechen Wang,1 Chunmao Han,2,3 Shoujie Wang1,4 1Department of Plastic Surgery, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, Zhejiang University, Yiwu, Zhejiang, People’s Republic of China; 2Department of Burns & Wound Care Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Plastic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shoujie Wang; Chunmao Han, Email wangshoujie@zju.edu.cn; zrssk@zju.edu.cnAbstract: Tissue injury repair is a multifaceted and dynamic process characterized by complex interactions among various immune cells, with M2 macrophages assuming a crucial role. Exosomes derived from M2-type macrophages (M2-Exos) significantly influence the injury repair process through intercellular communication mediated by enriched microRNAs (miRNAs). This review aims to elucidate the biological processes underlying exosome formation, the synthesis and function of miRNAs, and the diverse methodologies employed for exosome extraction. Furthermore, we provide a comprehensive summary of the established multifarious functions and mechanisms of M2-Exos miRNAs in tissue injury repair across different systems, while also exploring their potential applications in disease prevention, diagnosis, and clinical practice. Despite the challenges encountered, the therapeutic use of M2-Exos in clinical contexts appears promising, prompting research efforts to focus on improving the efficiency of exosome extraction and application, as well as ensuring the safety of their clinical utilization.Keywords: M2 macrophages, exosomes, miRNAs, tissue repair, drug delivery systems, engineered exosome

BACKGROUND: Research on adipose-derived mesenchymal stem cells and their exosomes often uses proteomics to analyze their roles in tissue repair, but comparative proteomic analyses between the two are scarce. OBJECTIVE: To analyze adipose-derived mesenchymal stem cells and their exosomes using proteomic analysis. METHODS: Rat adipose-derived mesenchymal stem cells were isolated, cultured, and identified. Exosomes were then extracted from cell supernatant and identified. Differentially expressed proteins of adipose-derived mesenchymal stem cells and their exosomes were analyzed using DIA proteomics. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed on these differentially expressed proteins. RESULTS AND CONCLUSION: (1) Adipose-derived mesenchymal stem cells displayed a mainly spindle-shaped, fibroblast-like morphology. (2) The exosome suspension protein concentration was 7.66 mg/mL, as determined by the BCA method. (3) Exosomes exhibited a characteristic teacup shape with a visible double-layer membrane vesicle structure. The center presented a low electron density component. The exosomes showed a peak particle size distribution of 112.2 nm, a concentration of 7.5×1011 particles/mL, and an average diameter ranging from 70 to 140 nm. (4) Exosomes expressed high levels of surface marker proteins CD9 and TSG101. (5) Gene Ontology analysis of differentially expressed proteins revealed enrichment in the extracellular matrix and synapses, with functions related to ion binding, ribosome binding, and particularly cell adhesion and translation. (6) Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the differentially expressed proteins were primarily involved in extracellular matrix receptor interaction, ribosome, and cytokine receptor interaction, and also associated with various metabolic diseases like cholesterol and thyroid disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: A large number of studies have confirmed that the therapeutic effectiveness of mesenchymal stem cell secretome is comparable to that of mesenchymal stem cells, but the mechanism of its action is still unclear. OBJECTIVE: To summarize the research progress of mesenchymal stem cell secretome in recent years, to investigate the molecular mechanism of its therapeutic effect, to analyze the current problems and to look forward to the future development. METHODS: The terms “exosomes, mesenchymal stem cells secrete, extracellular vesicles, mesenchymal stem cells, mechanism” were used as English search terms in the PubMed database. Articles that were not related to the research purpose of the article and duplicated articles were excluded. At the same time, we combined the method of literature tracking. Finally, 109 articles that met the criteria were incuded for the review. RESULTS AND CONCLUSION: (1) The mesenchymal stem cell secretome promotes tissue repair and regeneration through delivering genetic material, immunomodulatory factors, growth factors, etc. to target cells, by activating anti-apoptotic, regulating angiogenesis, modulating fibrosis and pro-survival pathways in target cells. (2) The potential of mesenchymal stem cell secretome in disease therapy has also been confirmed. Numerous research results have shown that mesenchymal stem cell secretome can be used as a new cell-free treatment for inflammatory and degenerative diseases. (3) Mesenchymal stem cell secretome has been engineered to have more efficient therapeutic effects in recent years. However, due to the heterogeneity of the mesenchymal stem cell secretome and the complexity of its components, the exact mechanism of its therapeutic effect is still unclear. (4) At present, further research is needed to identify the key targets of mesenchymal stem cell secretome, and innovative specific and enhanced mesenchymal stem cell secretome should be developed by combining with engineering and genetic engineering technologies in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND: During tissue repair and regeneration, macrophages exhibit multiple activities such as promoting inflammation, anti-inflammation, fibrosis, and wound healing at various stages of tissue damage. The heterogeneity and balanced polarization of macrophages are decisive in organ repair. OBJECTIVE: To explore the research hotspots and development trends in the field of macrophage polarization in tissue repair through visualization analysis methods, as well as the research level of global scientific and clinical workers in this field. METHODS: Using bibliometric analysis methods, this study employed Citespace literature visualization analysis software and VOSviewer tools, retrieving related literature from 2013 to 2023 in the Web of Science Core Collection’s Science Citation Index Expanded (SCI-Expanded) and Social Sciences Citation Index Expanded (SSCI-Expanded) databases. The analysis results were presented in a dynamic map format, revealing the main trends and focuses of the research. RESULTS AND CONCLUSION: The number of publications in this field had dramatically increased from 2013 to 2023, with a significant rise starting in 2017. Chinese researchers had the highest number of publications, with 642 papers, while American researchers began focusing on this field early on. Professor Elisseeff Hennifer H had made a substantial contribution to the research in this area. Shanghai Jiao Tong University had produced the most publications. In recent years, keywords such as “hyaluronic acid” and “regulation” had been prevalent. Macrophage polarization research in tissue repair primarily concentrates on its multifunctional regulatory mechanisms, interactions with other cell types, and its behavior under specific pathological conditions. The main research areas include the role of macrophages in wound healing, cardiovascular diseases, chronic inflammation, tumor microenvironments, and regenerative medicine. A deeper understanding of the multifunctionality and polarization mechanisms of macrophages can lead to the development of new therapeutic strategies to enhance tissue repair and regeneration, thereby improving patient treatment outcomes. [ABSTRACT FROM AUTHOR]

Regenerative medicine has immense potential to revolutionize healthcare by using regenerative capabilities of stem cells. Microfluidics, a cutting-edge technology, offers precise control over cellular microenvironments. The integration of these two fields provides a deep understanding of stem cell behavior and enables the development of advanced therapeutic strategies. This critical review explores the use of microfluidic systems to culture and differentiate stem cells with precision. We examined the use of microfluidic platforms for controlled nutrient supply, mechanical stimuli, and real-time monitoring, providing an unprecedented level of detail in studying cellular responses. The convergence of stem cells and microfluidics holds immense promise for tissue repair, regeneration, and personalized medicine. It offers a unique opportunity to revolutionize the approach to regenerative medicine, facilitating the development of advanced therapeutic strategies and enhancing healthcare outcomes. [ABSTRACT FROM AUTHOR]

Abstract Purpose This study investigates the effects of hexagonal microtextured titanium sheets on fibroblast growth and collagen synthesis, crucial factors in anastomotic healing. Materials and methods Hexagonal titanium sheets were fabricated using a laser microtextured machine. Mouse fibroblastic embryonic stem cells (NIH/3T3) were cultured on these sheets. Cell proliferation was assessed using a CCK8 assay, and expression of TGF-β/Smad pathway-related genes and collagen types I and III was evaluated through qRT-PCR and western blot. Results Hexagonal titanium sheets significantly enhanced fibroblast growth and collagen synthesis. The 50–30 group, with the smallest contact angle (48 ± 2.3°), exhibited the highest cell growth rates by CCK8 assay. Gene expression analysis revealed that TGF-β1, Smad2, Smad3, Smad4, and COL1A1 were significantly upregulated in the 50–30 group on day 7. Meanwhile, type I collagen expression was significantly increased in the 50–30 group on day 7 by western blot analysis. Conclusion Our findings demonstrate that laser-fabricated hexagonal microtextured titanium sheets enhance hydrophilicity and promote fibroblast growth, activating the TGF-β/Smad pathway to facilitate collagen synthesis. These results have important implications for tissue repair and regeneration.

Qingpeng Xie,1,2,* Jiawen Gu,1,2,* Yujia Sun,3 Jinjia Hong,1,2 Jia Wang,1,2 Na Li,1,2 Yuan Zhang,1,2 Meixian Liu,1,2 Xiaoxuan Zhang,1,2 Xiangyu Zhao,1,2 Xiaohang Chen,1,2 Xing Wang1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, People’s Republic of China; 3Nursing College of Shanxi Medical University, Taiyuan, 030001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohang Chen; Xing Wang, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China, Tel +8618834896163 ; +8613934224604, Email kqyx__cxh@163.com; wangxing@sxmu.edu.cnPurpose: Periodontitis is a chronic inflammatory oral disease that causes defects in periodontal tissue. Conventional therapies are limited, and often lead to high recurrence rates. The emerging concept of medicinal food homology has shed light on the potential of ginger as a therapeutic adjuvant for periodontitis, given its antioxidant and anti-inflammatory properties. However, fresh ginger exhibits poor stability and bioavailability. Ginger exosome-like nanoparticles (GELNs), a derivative of ginger, have not been reported to exert therapeutic effects in periodontitis. This study aimed to explore the therapeutic effects of GELNs on tissue damage caused by periodontitis and their underlying mechanisms of action.Methods: The GELNs composition was analyzed using a widely targeted metabolome. Stability was assessed using nanoparticle tracking analysis (NTA) and zeta potential measurements, flavor was evaluated using an electronic nose, and membrane penetration was studied using confocal microscopy. A periodontitis model was established in SD rats, periodontal clinical indicators were monitored, and histological changes were assessed using H&E and TRAP staining. Co-culture experiments investigate the antioxidant and reparative abilities of GELNs on periodontal ligament fibroblasts (PDLFs) in inflammatory environment. NF-κB protein expression was examined by immunofluorescence and immunohistochemistry.Results: The findings revealed that GELNs demonstrated good stability in different environments and mitigated the pungent taste of the raw ginger. In vivo experiments showed that GELNs improved periodontal clinical parameters and pathology compared with ginger juice. In vitro data suggested that GELNs enhanced the proliferation and migration of PDLFs while reducing the reactive oxygen species (ROS) levels by inhibiting the NF-κB signaling pathway in an inflammatory setting.Conclusion: This study is the first to demonstrate that GELNs have a potential therapeutic effect on periodontitis. GELNs can alleviate oxidative stress (OS) and inflammatory reactions by inhibiting the NF-κB signaling pathway. These findings provide a promising method for the treatment of periodontitis by regulating an unbalanced OS state. Keywords: ginger exosome-like nanoparticles, periodontitis, tissue repair, oxidative stress, periodontal ligament fibroblasts

Osteoarthritis is a joint disease that causes pain, stiffness, and reduced joint function because the protective cushioning inside the joints, called cartilage, gradually wears away. This condition is caused by various factors and complex processes in the joint’s environment, involving different types of cells producing factors that can either maintain the joint health or contribute to osteoarthritis. This study aimed to understand the factors influencing both healthy and diseased joints in DDD strategies for the in vitro preconditioning of MSCs. An electronic search in the PubMed, Scopus, and Web of Science databases was carried out using the terms (cartilage OR chondr*) AND (repair OR regeneration OR healing) AND (niche OR microenvironment)) AND (“growth factor” OR GF OR cytokine). Researchers used various methods, including macroscopic examinations, histology, immunohistochemistry, and microCT. Molecules associated with joint inflammation were identified, like macrophage markers, MMP-13, TNF, apoptotic markers, and interleukins. Chondrogenesis-related factors such as aggrecan GAG, collagen type II, and TGF beta family were also identified. This study suggests that balancing certain molecules and ensuring the survival of joint chondrocytes could be crucial in improving the condition of osteoarthritic joints, emphasizing the importance of chondrocyte survival and activity. Future preconditioning methods for MSC- and EV-based therapies can find suitable strategies in the described microenvironments to explore co-culture systems and soluble or extracellular matrix factors.

Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lack of effective strategies to cope with due to its high requirements of sterilization, soft tissue healing, and osseointegration. In this work, l-arginine (L-Arg) was loaded onto a sulfonated polyetheretherketone (PEEK) surface to solve this issue. Under the infection condition, nitric oxide (NO) and reactive oxygen species (ROS) are produced through catalyzing L-Arg by inducible nitric oxide synthase (iNOS) and thus play a role in bacteria sterilization. Under the tissue repair condition, L-Arg is catalyzed to ornithine by Arginase-1 (Arg-1), which promotes the proliferation and collagen secretion of L929 and rBMSCs. Notably, L-Arg loading samples could polarize macrophages to M1 and M2 in infection and tissue repair conditions, respectively. The results in vivo show that the L-Arg loading samples could enhance infected soft tissue sealing and bone regeneration. In summary, L-Arg loading sulfonated PEEK could polarize macrophage through metabolic reprogramming, providing multi-functions of antibacterial abilities, soft tissue repair, and bone regeneration, which gives a new idea to design percutaneous implantation materials.

Tissue engineering technology has advanced rapidly in recent years, offering opportunities to construct biologically active tissues or organ substitutes to repair or even enhance the functions of diseased tissues and organs. Tissue-engineered scaffolds rebuild the extracellular microenvironment by mimicking the extracellular matrix. Fibrin-based scaffolds possess numerous advantages, including hemostasis, high biocompatibility, and good degradability. Fibrin scaffolds provide an initial matrix that facilitates cell migration, differentiation, proliferation, and adhesion, and also play a critical role in cell-matrix interactions. Fibrin scaffolds are now widely recognized as a key component in tissue engineering, where they can facilitate tissue and organ defect repair. This review introduces the properties of fibrin, including its composition, structure, and biology. In addition, the modification and cross-linking modes of fibrin are discussed, along with various forms commonly used in tissue engineering. We also describe the biofunctionalization of fibrin. This review provides a detailed overview of the use and applications of fibrin in skin, bone, and nervous tissues, and provides novel insights into future research directions for clinical treatment.

Microcarrier applications have made great advances in tissue engineering in recent years, which can load cells, drugs, and bioactive factors. These microcarriers can be minimally injected into the defect to help reconstruct a good microenvironment for tissue repair. In order to achieve more ideal performance and face more complex tissue damage, an increasing amount of effort has been focused on microcarriers that can actively respond to external stimuli. These microcarriers have the functions of directional movement, targeted enrichment, material release control, and providing signals conducive to tissue repair. Given the high controllability and designability of magnetic and electroactive microcarriers, the research progress of these microcarriers is highlighted in this review. Their structure, function and applications, potential tissue repair mechanisms, and challenges are discussed. In summary, through the design with clinical translation ability, meaningful and comprehensive experimental characterization, and in-depth study and application of tissue repair mechanisms, stimuli-responsive microcarriers have great potential in tissue repair.

Abstract The aryl hydrocarbon receptor is a ligand dependent transcription factor which functions as an environmental sensor. Originally discovered as the sensor for man made pollutants such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) it has recently gained prominence as an important mediator for environmental triggers via the diet or microbiota which influences many physiological functions in different cell types and tissues across the body. Notably AHR activity contributes to prevent excessive inflammation following tissue damage in barrier organs such as skin, lung or gut which has received wide attention in the past decade. In this review we will focus on emerging common AHR functions across cell types and tissues and discuss ongoing issues that confound the understanding of AHR physiology. Furthermore, we will discuss the need for deeper molecular understanding of the functional activity of AHR in different contexts with respect to development of potential therapeutic applications.

Purpose: This study investigates the effects of hexagonal microtextured titanium sheets on fibroblast growth and collagen synthesis, crucial factors in anastomotic healing. Materials and methods: Hexagonal titanium sheets were fabricated using a laser microtextured machine. Mouse fibroblastic embryonic stem cells (NIH/3T3) were cultured on these sheets. Cell proliferation was assessed using a CCK8 assay, and expression of TGF-β/Smad pathway-related genes and collagen types I and III was evaluated through qRT-PCR and western blot. Results: Hexagonal titanium sheets significantly enhanced fibroblast growth and collagen synthesis. The 50–30 group, with the smallest contact angle (48 ± 2.3°), exhibited the highest cell growth rates by CCK8 assay. Gene expression analysis revealed that TGF-β1, Smad2, Smad3, Smad4, and COL1A1 were significantly upregulated in the 50–30 group on day 7. Meanwhile, type I collagen expression was significantly increased in the 50–30 group on day 7 by western blot analysis. Conclusion: Our findings demonstrate that laser-fabricated hexagonal microtextured titanium sheets enhance hydrophilicity and promote fibroblast growth, activating the TGF-β/Smad pathway to facilitate collagen synthesis. These results have important implications for tissue repair and regeneration. [ABSTRACT FROM AUTHOR]

The human fetal membrane is a globally accepted biological biomaterial for wound and tissue repair and regeneration in numerous fields, including dermatology, ophthalmology, and more recently orthopedics, maxillofacial and oral surgery, and nerve regeneration. Both cells and matrix components of amnion and chorion are beneficial, releasing a diverse range of growth factors, cytokines, peptides, and soluble extracellular matrix components. Beside fetal membranes, numerous natural materials have also been reported to promote wound healing. The biological properties of these materials may potentiate the pro-healing action of fetal membranes. Comparison of such materials with fetal membranes has been scant, and their combined use with fetal membranes has been underexplored. This review presents an up-to-date overview of (i) clinical applications of human fetal membranes in wound healing and tissue regeneration; (ii) studies comparing human fetal membranes with natural materials for promoting wound healing; and (iii) the literature on the combined use of fetal membranes and natural pro-healing materials. [ABSTRACT FROM AUTHOR]

Chronic or non-healing wounds, such as diabetic foot ulcers (DFUs), venous leg ulcers (VLUs), pressure ulcers (PUs) and wounds in the elderly etc., impose significant biological, social, and financial burdens on patients and their families. Despite ongoing efforts, effective treatments for these wounds remain elusive, costing the United States over US$25 billion annually. The wound healing process is notably slower in the elderly, partly due to cellular senescence, which plays a complex role in wound repair. High glucose levels, reactive oxygen species, and persistent inflammation are key factors that induce cellular senescence, contributing to chronic wound failure. This suggests that cellular senescence may not only drive age-related phenotypes and pathology but also be a key mediator of the decreased capacity for trauma repair. This review analyzes four aspects: characteristics of cellular senescence; cytotoxic stressors and related signaling pathways; the relationship between cellular senescence and typical chronic non-healing wounds; and current and future treatment strategies. In theory, anti-aging therapy may influence the process of chronic wound healing. However, the underlying molecular mechanism is not well understood. This review summarizes the relationship between cellular senescence and chronic wound healing to contribute to a better understanding of the mechanisms of chronic wound healing. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) represents a severe neurological condition often coupled with a drastic secondary inflammatory response, which further exacerbates the damage in most cases. Due to their unique electrical and mechanical compatibilities with the spinal cord, the utilization of conductive hydrogels through injection for SCI repair, particularly in scenarios involving non‐uniform and large gaps, has emerged as a promising approach. Herein, leveraging the acidic microenvironment characteristic of acute SCI sites, an injectable conductive hydrogel with pH‐responsive immunoregulation is engineered for SCI repair. Based on the dynamic Schiff base chemistry and covalent photo‐crosslinking, this composite hydrogel, composed of gelatin methacryloyl, oxidized dextran, and MoS2, exhibits adjustable mechanical and conductive properties, enabling a customized match with the natural spinal cord's attributes. Additionally, the incorporation of Wnt5a and its selective release in acidic conditions prompt the immediate suppression of inflammatory factors and enhances neural differentiation and regeneration. In the 2‐mm hemisection mouse SCI model, the optimized conductive hydrogel can effectively bridge the injury gap, establish nerve connections and signal, mitigate inflammatory response, and promoted recovery of mobility. This novel injectable conductive hydrogel system offers a promising advance in therapeutic materials for SCI repair. [ABSTRACT FROM AUTHOR]

Stroke and traumatic brain injury leave many survivors with permanent neurological disabilities, and the development of therapeutics to enhance functional recovery is needed. Both residential and infiltrating immune cells participate in the acute inflammation after brain injury, exacerbating functional outcomes; however, some immune cells have been reported to alter their characteristic to a reparative phenotype. This review focused on the recent findings of the reparative immunity of myeloid cells. Functional recovery after injury is achieved through the combination of resolution of inflammation, reorganization of neuronal network, white matter repair, angiogenesis and extracellular matrix reorganization. In each process, myeloid cells play vital roles in leading to functional recovery. Further research on the diversity of immune cells implicated in neural repair will be promising to develop therapeutics enhancing functional recovery after brain tissue injuries. [ABSTRACT FROM AUTHOR]

[Display omitted] Monodisperse nanoparticles of biodegradable polyhydroxyalkanoates (PHAs) polymers, copolymers of 3-hydroxybutyrate (3HB) and 4-hydroxybutyrate (4HB), are synthesized using a membrane-assisted emulsion encapsulation and evaporation process for biomedical resorbable adhesives. The precise control over the diameter of these PHA particles, ranging from 100 nm to 8 μm, is achieved by adjusting the diameter of emulsion or the PHA concentration. Mechanical properties of the particles can be tailored based on the 3HB to 4HB ratio and molecular weight, primarily influenced by the level of crystallinity. These monodisperse PHA particles in solution serve as adhesives for hydrogel systems, specifically those based on poly(N , N -dimethylacrylamide) (PDMA). Semi-crystalline PHA nanoparticles exhibit stronger adhesion energy than their amorphous counterparts. Due to their self-adhesiveness, adhesion energy increases even when those PHA nanoparticles form multilayers between hydrogels. Furthermore, as they degrade and are resorbed into the body, the PHA nanoparticles demonstrate efficacy in in vivo wound closure, underscoring their considerable impact on biomedical applications. [ABSTRACT FROM AUTHOR]

[Display omitted] Multifunctional bioactive biomaterials with integrated bone and soft tissue regenerability hold great promise for the regeneration of trauma-affected skin and bone defects. The aim of this research was to fabricate aerogel scaffolds (GD-BF) by blending the appropriate proportions of short bioactive glass fiber (BGF), gelatin (Gel), and dopamine (DA). Electrospun polyvinyl pyrrolidone (PVP)-BGF fibers were converted into short BGF through calcination and homogenization. Microporous GD-BF scaffolds displayed good elastic deformation recovery and promoted neo-tissue formation. The DA could enable thermal crosslinking and enhance the mechanical properties and structural stability of the GD-BF scaffolds. The BGF-mediated release of therapeutic ions shorten hemostatic time (<30 s) in a rat tail amputation model and a rabbit artery injury model alongside inducing the regeneration of skin appendages (e.g., blood vessels, glands, etc.) in a full-thickness excisional defect model in rats (percentage wound closure: GD-BF2, 98 % vs. control group, 83 %) at day 14 in vitro. Taken together, these aerogel scaffolds may have significant promise for soft and hard tissue repair, which may also be worthy for the other related disciplines. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is a critical global health issue and a leading cause of heart failure. Indeed, while neonatal mammals can regenerate cardiac tissue mainly through cardiomyocyte proliferation, this ability is lost shortly after birth, resulting in the adult heart's inability to regenerate after injury effectively. In adult mammals, the adverse cardiac remodelling, which compensates for the loss of cardiac cells, impairs cardiac function due to the non-contractile nature of fibrotic tissue. Moreover, the neovascularisation after MI is inadequate to restore blood flow to the infarcted myocardium. This review aims to synthesise the most recent insights into the molecular and cellular players involved in endogenous myocardial and vascular regeneration, facilitating the identification of mechanisms that could be targeted to trigger cardiac regeneration, reduce fibrosis, and improve functional recovery post-MI. Reprogramming adult cardiomyocytes to regain their proliferative potential, along with the modulation of target cells responsible for neovascularisation, represents promising therapeutic strategies. An updated overview of endogenous mechanisms that regulate both myocardial and coronary vasculature regeneration—including stem and progenitor cells, growth factors, cell cycle regulators, and key signalling pathways—could help identify new critical intervention points for therapeutic applications. [ABSTRACT FROM AUTHOR]