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Self-organizing three-dimensional dermal papilla cell spheroids yield therapeutic extracellular vesicles that target hypertrophic scar regression via the miR-26a-5p/CCNE2 axis
Burns & Trauma 2026, 14(3): tkaf048
Published: 22 July 2025
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Background

Hypertrophic scarring remains a critical challenge in regenerative medicine because of the limited efficacy of current antifibrotic therapies. Although dermal papilla cells (DPCs) exhibit intrinsic scar-inhibitory potential, their therapeutic utility is constrained by rapid replicative senescence and poor scalability in traditional monolayer cultures, necessitating innovative strategies to enhance cellular functionality and manufacturing feasibility.

Methods

A self-feeder layer 3D (SFL-3D) platform was established to reprogram primary human DPCs into rejuvenated three-dimensional DPC (tdDPC) spheroids via autocrine–paracrine signalling activation. tdDPC-derived extracellular vesicles (tdDPC-EVs) were isolated from culture supernatants by differential centrifugation. The antifibrotic effects of tdDPC-EVs were systematically evaluated using human scar fibroblasts through scratch wound healing assays, CCK-8 proliferation assays, and fibrotic marker analysis [Western blotting and immunofluorescence staining for α-smooth muscle actin (α-SMA) and collagen I]. Bioinformatics was used to predict key pathways involved in hypertrophic scar (HS) pathogenesis, whereas gain/loss-of-function studies investigated the miR-26a-5p/CCNE2 regulatory axis. Therapeutic validation was performed in a rabbit ear hypertrophic scar model with histopathological and molecular profiling.

Results

Compared with conventional 3D cultures, the SFL-3D system demonstrated superior proliferative support, enabling stable tdDPC expansion beyond 10 passages while maintaining high viability and enhanced EV biogenesis. miR-26a-5p-enriched tdDPC-EVs attenuated fibrosis through two mechanisms: (1) silencing CCNE2 to block PI3K/AKT-driven collagen overproduction and (2) suppressing α-SMA + myofibroblast differentiation. In the rabbit ear HS model, tdDPC-EV administration reduced the scar elevation index and restored the collagen Ⅰ/Ⅲ ratio to near-physiological levels.

Conclusions

This study positions tdDPC-EVs as a scalable acellular therapy that overcomes the replicative senescence and manufacturing limitations of cellular approaches. The antiscarring efficacy of these EVs, which is mediated by the miR-26a-5p/CCNE2/PI3K/AKT axis, highlights their clinical potential as precision-targeted strategies for hypertrophic scar management. The SFL-3D platform further provides a translatable framework for EV-based regenerative therapeutics.

Issue
Clinical Summary of 186 Cases of Orbital Autologous Fat Injection Transplantation Safely Implemented by Boosters
Medical Journal of Peking Union Medical College Hospital 2024, 15(6): 1342-1347
Published: 29 October 2024
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Objective

To summarize the clinical effect of using boosters for orbital autologous fat injection transplantation.

Methods

A retrospective analysis was conducted on the clinical data of patients who underwent orbital fine autologous fat injection and transplantation at the Burn and Plastic Surgery Department of the 940th Hospital of the PLA Joint Logistics Support Force from January 2019 to December 2023. The patients were treated with orbital fine autologous fat injection and transplantation using a self-developed autologous fat transplantation booster with constant pressure and micro controllability connected to a 1 mL injector, and the therapeutic effect was analyzed.

Results

A total of 186 patients who met the inclusion and exclusion criteria were included in this study, including 165 females and 21 males, with the average age of (39.0±7.1) years old (range: 23-71 years old). Of the 186 patients, 58 cases were of upper eyelid depression, 45 cases were of inner canthal depression, 34 cases were of ocular platform flattening, 6 cases were of meibomian depression, and 43 cases were of lacrimal groove depression. The transplantation volume of granular fat was 0.1-10 mL, with an average of 3.5 mL; the injection volume of nanofat was 0.5-2.0 mL, with an average of 0.5 mL. Follow up for 7 days to 4 years showed that 163 cases (87.6%) were satisfied with the results, 15 cases (8.1%) had average results, and 8 cases (4.3%) were dissatisfied. No surgical complications occurred.

Conclusion

The use of a constant pressure and micro controllable electric booster to assist autologous fat injection transplantation could achieve precision in orbital autologous fat transplantation, with high patient satisfaction, meaning that it is worthy of clinical promotion and application.

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