Research ArticleBIOMATERIALS

Nanofiber-hydrogel composite–mediated angiogenesis for soft tissue reconstruction

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Science Translational Medicine  01 May 2019:
Vol. 11, Issue 490, eaau6210
DOI: 10.1126/scitranslmed.aau6210

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Crafting a (re)constructive composite

To be useful for soft tissue reconstruction, a biomaterial should be compatible with surgical manipulation while providing material properties similar to the native tissue and should not promote scarring or adverse cell activation. Toward this goal, Li et al, developed an injectable, biodegradable composite biomaterial composed of hyaluronic acid hydrogel with embedded synthetic polymer fibers. Human cells formed vascular-like networks within the material in vitro, and subcutaneously implanted material showed macrophage infiltration and angiogenesis in rats. Macrophages were polarized toward a pro-regenerative phenotype, and the material facilitated adipose soft tissue defect repair in a rabbit model.

Abstract

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.

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