Format

Send to

Choose Destination
Sci Transl Med. 2019 May 1;11(490). pii: eaau6210. doi: 10.1126/scitranslmed.aau6210.

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

Li X1,2,3, Cho B4, Martin R1,2,3, Seu M4, Zhang C1,2,3, Zhou Z1,2,3, Choi JS1,2,3, Jiang X1,2,3, Chen L1,2,3, Walia G4, Yan J5, Callanan M5, Liu H1,2,3, Colbert K1,2, Morrissette-McAlmon J1,5, Grayson W1,2,5, Reddy S6, Sacks JM6, Mao HQ7,2,3,5.

Author information

1
Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
2
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
3
Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
4
Department of Plastic and Reconstructive Surgery, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
5
Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
6
Department of Plastic and Reconstructive Surgery, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA. hmao@jhu.edu jmsacks@jhmi.edu sreddy6@jhmi.edu.
7
Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA. hmao@jhu.edu jmsacks@jhmi.edu sreddy6@jhmi.edu.

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.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center