Injectable Silk Nanofiber Hydrogels for Sustained Release of Small-Molecule Drugs and Vascularization

Ding, Zhaozhao; Zhou, Mingliang; Zhou, Zhengyu; Zhang, Wenjie; Jiang, Xinquan; Lü, Xiaohong; Zuo, Baoqi; Lü, Qiang; Kaplan, David L.

doi:10.1021/acsbiomaterials.9b00621

Cited by 68 publications

(110 citation statements)

References 72 publications

(180 reference statements)

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“…Cell‐free SFN hydrogels as matrices have been used to accelerate wound healing. [ 12,13 ] To reveal the synergistic action of SFN, LP, and BMSCs, cell‐free SFN and SFN‐LP hydrogels, BMSCs in medium, BMSCs‐laden SFN hydrogels, and BMSCs‐laden SFN‐LP hydrogels were used to fill full‐thickness wounds. Since all the wounds healed completely within 21 days ( Figure a,b), the rats were reared for 21 days to evaluate the wound healing quality.…”

Section: Resultsmentioning

confidence: 99%

“…The stability of the SFN and SFN‐P composite hydrogels was assessed by measuring the rheological behavior under constant frequency over the temperate range of 22–40 °C. [ 12,13,19 ]…”

Section: Methodsmentioning

confidence: 99%

“…Nine to ten week old Sparague‐Dawley (SD) adult male rats were used for the in vivo wound experiments. [ 12,13 ] All animal experiments were approved by the Animal Care and Experiment Committee of the Soochow university (approval number 201905A182, 201906A340, and 201907A108, Suzhou, China). Thirty SD rats were randomly distributed to six groups: blank, SFN, SFN‐LP hydrogels, BMSCs in medium, BMSCs blended with SFN hydrogels (SFN‐BMSCs hydrogels), and BMSC‐loaded on LP particles and then blended with SFN hydrogels (SFN‐LP‐BMSCs hydrogels).…”

Section: Methodsmentioning

confidence: 99%

“…CD31, CD68, and CD206 immunofluorescence staining were performed according to previous studies. [ 5a,12,13 ] H&E stained sections were used to evaluate new epidermis formation in each group. Masson's trichrome and Picrosirius Red stained sections were used to evaluate collagen synthesis and collagen type III/I radio in each group.…”

Section: Methodsmentioning

confidence: 99%

“…Both SFN‐based scaffolds and hydrogels were fabricated to stimulate tissue ingrowth, resulting in better wound healing. [ 12,13 ] SFN hydrogels with aligned topography were then developed in our group to form better niches with multiple cues. [ 14 ] Unlike unaligned SFN hydrogels, the aligned SFN hydrogels could regulate the secretion of different cytokines and growth factors from SCs, achieving long‐term stemness of the SCs without exogeneous grow factors and fibroblasts (data not shown).…”

Section: Introductionmentioning

confidence: 99%

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Microskin‐Inspired Injectable MSC‐Laden Hydrogels for Scarless Wound Healing with Hair Follicles

Zheng

Ding

Cheng

et al. 2020

Adv Healthcare Materials

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Scarless skin regeneration with functional tissue remains a challenge for full-thickness wounds. Here, mesenchymal stem cell (MSC)-laden hydrogels are developed for scarless wound healing with hair follicles. Microgels composed of aligned silk nanofibers are used to load MSCs to modulate the paracrine. MSC-laden microgels are dispersed into injectable silk nanofiber hydrogels, forming composites biomaterials containing the cells. The injectable hydrogels protect and stabilize the MSCs in the wounds. The synergistic action of silk-based composite hydrogels and MSCs stimulated angiogenesis and M1-M2 phenotype switching of macrophages, provides a suitable niche for functional recovery of wounds. Compared to skin defects treated with MSC-free hydrogels, the defects treated with the MSC-laden composite hydrogels heal faster and form scarless tissues with hair follicles. Wound healing can be further improved by adjusting the ratio of silk nanofibers and particles and the loaded MSCs, suggesting tunability of the system. To the best of current knowledge, this is the first time scarless skin regeneration with hair follicles based on silk material systems is reported. The improved wound healing capacity of the systems suggests future in vivo studies to compare to other biomaterial systems related to clinical goals in skin regeneration in the absence of scarring.

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Section: Resultsmentioning

confidence: 99%

“…The stability of the SFN and SFN‐P composite hydrogels was assessed by measuring the rheological behavior under constant frequency over the temperate range of 22–40 °C. [ 12,13,19 ]…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microskin‐Inspired Injectable MSC‐Laden Hydrogels for Scarless Wound Healing with Hair Follicles

Zheng

Ding

Cheng

et al. 2020

Adv Healthcare Materials

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Biomimetic Vascular Grafts with Circumferentially and Axially Oriented Microporous Structures for Native Blood Vessel Regeneration

Ding,

Wang,

Chen

et al. 2023

Adv Funct Materials

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Porous grafts facilitate constructive remodeling of blood vessels. Incorporating multiple biomimetic cues to porous grafts can promote vascular regeneration. However, the fabrication of such medical devices remains challenging. Here, beta‐sheet rich silk nanofibers (BSN) are added to poly(vinyl alcohol) (PVA) solution and aggregated under a cylindric electric field to form circumferentially and axially oriented tubular structures, to simulate the endothelial and media layers of blood vessels. PVA in the aligned tubes is then crystallized through repeat freezing–thawing process to offer mechanical performances. Through tuning the ratio of BSN and PVA, the composite tubes with dual anisotropic microstructures exhibit better mechanical properties than pure PVA vascular grafts. Significantly improved cell adhesion, spreading, proliferation, and alignment are achieved. Both endothelial and smooth muscle cells show improved biological activity on the grafts due to the regulatory roles of the aligned structures. In vivo studies reveal the formation of endothelial layers within four weeks of implantation, ensuring long‐term patency. The endothelial and smooth muscle double layers are regenerated after eight months postimplantation, forming hierarchical microstructures and compositions similar to native vessels. The porous composite grafts with multiple aligned structures guide vascular remodeling to regenerate blood vessels, demonstrating potential for clinical translation.

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Recent Advances in Injectable Hydrogels for Controlled and Local Drug Delivery

Rizzo

Kehr

2020

Adv Healthcare Materials

200

152

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Injectable hydrogels have received considerable interest in the biomedical field due to their potential applications in minimally invasive local drug delivery, more precise implantation, and site‐specific drug delivery into poorly reachable tissue sites and into interface tissues, where wound healing takes a long time. Injectable hydrogels, such as in situ forming and/or shear‐thinning hydrogels, can be generated using chemically and/or physically crosslinked hydrogels. Yet, for controlled and local drug delivery applications, the ideal injectable hydrogel should be able to provide controlled and sustained release of drug molecules to the target site when needed and should limit nonspecific drug molecule distribution in healthy tissues. Thus, such hydrogels should sense the environmental changes that arise in disease states and be able to release the optimal amount of drug over the necessary time period to the target region. To address this, researchers have designed stimuli‐responsive injectable hydrogels. Stimuli‐responsive hydrogels change their shape or volume when they sense environmental stimuli, e.g., pH, temperature, light, electrical signals, or enzymatic changes, and deliver an optimal concentration of drugs to the target site without affecting healthy tissues.

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Injectable Silk Nanofiber Hydrogels for Sustained Release of Small-Molecule Drugs and Vascularization

Cited by 68 publications

References 72 publications

Microskin‐Inspired Injectable MSC‐Laden Hydrogels for Scarless Wound Healing with Hair Follicles

Microskin‐Inspired Injectable MSC‐Laden Hydrogels for Scarless Wound Healing with Hair Follicles

Biomimetic Vascular Grafts with Circumferentially and Axially Oriented Microporous Structures for Native Blood Vessel Regeneration

Recent Advances in Injectable Hydrogels for Controlled and Local Drug Delivery

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