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Evaluation and characterization of DDMH. (A) DDMH is in a liquid state at 4°C and in a gel state at 37°C. (B) HUVECs were inoculated and cultured with DDMH or TCP, and cell viability was detected with live/dead staining on the 3rd day. Scale bar: 100 μm (C) Quantitative analysis of cell viability. n = 4 per group. (D) CCK-8 assay was used to detect the proliferative capability of HUVECs seeded on DDMH and TCPs. n = 4 per group. (E) EVs released from DDMH or GH with time. (F) VEGF released from DDMH was detected by ELISA assay. (G) Immunogenicity of DDMH was detected by ELISA analysis of TNF-α, PGE-2, IL-6, and IL-1β levels. n = 4 per group. *p < 0.05, **p < 0.01, ***p < 0.001.
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Background: Insufficient blood supply results in unsatisfactory wound healing, especially for challenging wound repair such as diabetic wound defects. Regular exercise training brings a lot of benefits to cardiovascular fitness and metabolic health including attenuation of T2DM progression. Circulating extracellular vesicles (EVs) are postulated to...
Citations
Extracellular vesicles have shown promising tissue recovery-promoting effects, making them increasingly sought-after for their therapeutic potential in wound treatment. However, traditional extracellular vesicle applications suffer from limitations such as rapid degradation and short maintenance during wound administration. To address these challenges, a growing body of research highlights the role of hydrogels as effective carriers for sustained extracellular vesicle release, thereby facilitating wound healing. The combination of extracellular vesicles with hydrogels and the development of 3D bioprinting create composite hydrogel systems boasting excellent mechanical properties and biological activity, presenting a novel approach to wound healing and skin dressing. This comprehensive review explores the remarkable mechanical properties of hydrogels, specifically suited for loading extracellular vesicles. We delve into the diverse sources of extracellular vesicles and hydrogels, analyzing their integration within composite hydrogel formulations for wound treatment. Different composite methods as well as 3D bioprinting, adapted to varying conditions and construction strategies, are examined for their roles in promoting wound healing. The results highlight the potential of extracellular vesicle-laden hydrogels as advanced therapeutic tools in the field of wound treatment, offering both mechanical support and bioactive functions. By providing an in-depth examination of the various roles that these composite hydrogels can play in wound healing, this review sheds light on the promising directions for further research and development. Finally, we address the challenges associated with the application of composite hydrogels, along with emerging trends of 3D bioprinting in this domain. The discussion covers issues such as scalability, regulatory considerations, and the translation of this technology into practical clinical settings. In conclusion, this review underlines the significant contributions of hydrogel-mediated extracellular vesicle therapy to the field of 3D bioprinting and wound healing and tissue regeneration. It serves as a valuable resource for researchers and practitioners alike, fostering a deeper understanding of the potential benefits, applications, and challenges involved in utilizing composite hydrogels for wound treatment.
Graphical abstract
One of the complex challenges faced presently by tissue engineering (TE) is the development of vascularized constructs that accurately mimic the extracellular matrix (ECM) of native tissue in which they are inserted to promote vessel growth and, consequently, wound healing and tissue regeneration. TE technique is characterized by several stages, starting from the choice of cell culture and the more appropriate scaffold material that can adequately support and supply them with the necessary biological cues for microvessel development. The next step is to analyze the attained microvasculature, which is reliant on the available labeling and microscopy techniques to visualize the network, as well as metrics employed to characterize it. These are usually attained with the use of software, which has been cited in several works, although no clear standard procedure has been observed to promote the reproduction of the cell response analysis. The present review analyzes not only the various steps previously described in terms of the current standards for evaluation, but also surveys some of the available metrics and software used to quantify networks, along with the detection of analysis limitations and future improvements that could lead to considerable progress for angiogenesis evaluation and application in TE research.
In recent years, there has been a significant increase in the prevalence of chronic wounds, such as pressure ulcers, diabetic foot ulcers, and venous ulcers of the lower extremities. The main contributors to chronic wound formation are bacterial infection, prolonged inflammation, and peripheral vascular disease. However, effectively treating these chronic wounds remains a global challenge. Hydrogels have extensively explored as wound healing dressing because of their excellent biocompatibility and structural similarity to extracellular matrix (ECM). Nonetheless, much is still unknown how the hydrogels promote wound repair and regeneration. Signaling pathways play critical roles in wound healing process by controlling and coordinating cells and biomolecules. Hydrogels, along with their therapeutic ingredients that impact signaling pathways, have the potential to significantly enhance the wound healing process and its ultimate outcomes. Understanding this interaction will undoubtedly provide new insights into developing advanced hydrogels for wound repair and regeneration. In this paper, we review the latest studies on classical signaling pathways and potential targets influenced by hydrogel scaffolds in chronic wound healing. We hope this will offer a different perspective in developing more efficient hydrogels for treating chronic wounds.
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The severe quality of life and economic burden imposed by non‐healing skin wounds, infection risks, and treatment costs are affecting millions of patients worldwide. To mitigate these challenges, scientists are relentlessly seeking effective treatment measures. In recent years, extracellular vesicles (EVs) have emerged as a promising cell‐free therapy strategy, attracting extensive attention from researchers. EVs mediate intercellular communication, possessing excellent biocompatibility and stability. These features make EVs a potential tool for treating a plethora of diseases, including those related to wound repair. However, there is a growing focus on the engineering of EVs to overcome inherent limitations such as low production, relatively fixed content, and targeting capabilities of natural EVs. This engineering could improve both the effectiveness and specificity of EVs in wound repair treatments. In light of this, the present review will introduce the latest progress in the design methods and experimental paradigms of engineered EVs applied in wound repair. Furthermore, it will comprehensively analyze the current clinical research status and prospects of engineered EVs within this field.
