Nanofiber-hydrogel composite-mediated angiogenesis for soft tissue reconstruction.

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.

• Authors: Xiaowei Li, Brian Cho, Russell Martin, Michelle Seu, Chi Zhang, Zhengbing Zhou, Ji Suk Choi, Xuesong Jiang, Long Chen, Gurjot Walia, Jerry Yan, Megan Callanan, Huanhuan Liu, Kevin Colbert, Justin Morrissette-McAlmon, Warren Grayson, Sashank Reddy, Justin M Sacks, Hai-Quan Mao
• Journal: Science translational medicine (Sci Transl Med) Vol. 11 Issue 490 (05 01 2019) ISSN: 1946-6242 [Electronic] United States
• PMID: 31043572 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Chemical References

• Hydrogels

Topics

• Animals
• Cell Movement
• Cell Polarity
• Disease Models, Animal
• Gene Expression Regulation
• Hydrogels (chemistry)
• Macrophages (pathology)
• Models, Animal
• Nanofibers (chemistry, ultrastructure)
• Neovascularization, Physiologic (genetics)
• Phenotype
• Rabbits
• Rats
• Subcutaneous Tissue (pathology)
• Tissue Engineering