A high clinically translatable strategy to anti-aging using hyaluronic acid and silk fibroin co-crosslinked hydrogels as dermal regenerative fillers.
10.1016/j.apsb.2025.04.020
- Author:
Jialing CHENG
1
;
Zhiyang CHEN
1
;
Demin LIN
1
;
Yanfang YANG
1
;
Yanjing BAI
2
;
Lingshuang WANG
2
;
Jie LI
2
;
Yuchen WANG
1
;
Hongliang WANG
1
;
Youbai CHEN
3
;
Jun YE
1
;
Yuling LIU
1
Author Information
1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
2. Shenzhen Xiuli Medicine Technology Co., Ltd., Xinlan Community, Shenzhen 518110, China.
3. Department of Plastic and Reconstructive Surgery, Chinese PLA General Hospital, Beijing 100853, China.
- Publication Type:Journal Article
- Keywords:
Anti-aging;
Collagen regeneration;
Dermal filler;
Extracellular matrix remodeling;
Hyaluronic acid;
Hydrogel;
Silk fibroin;
Type III collagen
- From:
Acta Pharmaceutica Sinica B
2025;15(7):3767-3787
- CountryChina
- Language:English
-
Abstract:
An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.