Nanofiber-hydrogel composite–mediated angiogenesis for soft tissue reconstruction
Autor: | Justin M. Sacks, Jerry Yan, Zhengbing Zhou, Justin Morrissette-McAlmon, Long Chen, Xuesong Jiang, Xiaowei Li, Hai-Quan Mao, Kevin Colbert, Brian H. Cho, Chi Zhang, Russell Martin, Sashank Reddy, Huanhuan Liu, Ji Suk Choi, Megan Callanan, Warren L. Grayson, Gurjot S. Walia, Michelle Seu |
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Rok vydání: | 2019 |
Předmět: |
Angiogenesis
Nanofibers Neovascularization Physiologic 02 engineering and technology 010402 general chemistry 01 natural sciences Dermal Fillers Extracellular matrix chemistry.chemical_compound Subcutaneous Tissue Tissue engineering Cell Movement Fibrosis Hyaluronic acid medicine Animals Tissue Engineering Chemistry Macrophages Cell Polarity Soft tissue Hydrogels General Medicine 021001 nanoscience & nanotechnology medicine.disease Rats 0104 chemical sciences Disease Models Animal Phenotype Gene Expression Regulation Nanofiber Models Animal Rabbits 0210 nano-technology Biomedical engineering |
Zdroj: | Science Translational Medicine. 11 |
ISSN: | 1946-6242 1946-6234 |
Popis: | Soft tissue losses from tumor removal, trauma, aging, and congenital malformation affect millions of people each year. Existing options for soft tissue restoration have several drawbacks: Surgical options such as the use of autologous tissue flaps lead to donor site defects, prosthetic implants are prone to foreign body response leading to fibrosis, and fat grafting and dermal fillers are limited to small-volume defects and only provide transient volume restoration. In addition, large-volume fat grafting and other tissue-engineering attempts are hampered by poor vascular ingrowth. Currently, there are no off-the-shelf materials that can fill the volume lost in soft tissue defects while promoting early angiogenesis. Here, we report a nanofiber-hydrogel composite that addresses these issues. By incorporating interfacial bonding between electrospun poly(ε-caprolactone) fibers and a hyaluronic acid hydrogel network, we generated a composite that mimics the microarchitecture and mechanical properties of soft tissue extracellular matrix. Upon subcutaneous injection in a rat model, this composite permitted infiltration of host macrophages and conditioned them into the pro-regenerative phenotype. By secreting pro-angiogenic cytokines and growth factors, these polarized macrophages enabled gradual remodeling and replacement of the composite with vascularized soft tissue. Such host cell infiltration and angiogenesis were also observed in a rabbit model for repairing a soft tissue defect filled with the composite. This injectable nanofiber-hydrogel composite augments native tissue regenerative responses, thus enabling durable soft tissue restoration outcomes. |
Databáze: | OpenAIRE |
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