W e read with great interest the article published by Nie et al. titled "Preparing Adipogenic Hydrogel with Neo-Mechanical Isolated Adipose-Derived Extracellular Vesicles for Adipose Tissue Engineering." 1 We sincerely congratulate the authors on their contributions to the study of hydrogel and extracellular vesicles. Although the data presented by Nie and colleagues are encouraging, we still have some ideas and perspectives that we would like to share. So far, there indeed have been various studies on clinical treatments using extracellular vesicles and hydrogel. This has been a hot topic in recent years, and the conclusions have been positive. There are still some points we would like to discuss with the authors. First, in the animal model, 0.2 ml of adipose tissue-derived extracellular vesicle (ATEV)-decellularized adipose tissue hydrogel was injected subcutaneously into the right backs of mice, while the same volume of decellularized adipose tissue hydrogel was injected into the left backs; however, results showed there was no statistical difference between the two groups in adipose tissue volume retention. We would like to know more about the ATEVs' biological activity after decellularized adipose tissue hydrogel injection. It may be more convincing if the authors added a step to verify that the biological activity of the ATEVs did not change before the next injection. Second, hydrogel is a hot topic, and its biological functions have been widely studied. Many novel bioactive hydrogels have been reported, with some having the function of inducing adipose-derived stem cells into osteoblasts and some able to stimulate proliferation by imitating the extracellular matrix environment. 2 If most ATEVs survive, it shows that decellularized adipose tissue hydrogel possesses biological activities, such as promoting adipogenesis, stimulating ATEV proliferation, or something else. Further study of the biological mechanism may be needed. Finally, there are internationally recognized methods for the extraction of extracellular vesicles that have been approved by the International Vesicle Association, such as ultracentrifugation techniques, polymer precipitation, size-based isolation techniques, immunoaffinity chromatography, ultrafiltration, and the microfluidic technique. 3 We wonder, is the authors' method better at extracting quantity compared with these methods? A more efficient method is indeed needed at present.In conclusion, while the authors' neo-mechanical method for isolating ATEVs and preparing adipogenic hydrogel proved to be enlightening, more improvements and developments are necessary to lend this method credibility, reliability, and high-efficiency, either as a production machine to create business value or as a ready-off-the-shelf therapy for clinical treatments. This experience might be more complete if further research is conducted by the authors to identify specific pathways that promote adipogenesis and angiogenesis.