Nanofiber-hydrogel composite–mediated angiogenesis for soft tissue reconstruction

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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(-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.

Original languageEnglish (US)
Article numbereaau6210
JournalScience translational medicine
Volume11
Issue number490
DOIs
StatePublished - May 1 2019

Fingerprint

Nanofibers
Hydrogel
Fats
Macrophages
Angiogenesis Inducing Agents
Hyaluronic Acid
Subcutaneous Injections
Tissue Engineering
Foreign Bodies
Extracellular Matrix
Blood Vessels
Intercellular Signaling Peptides and Proteins
Fibrosis
Cytokines
Rabbits
Phenotype
Injections

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Nanofiber-hydrogel composite–mediated angiogenesis for soft tissue reconstruction. / Li, Xiaowei; Cho, Brian; Martin, Russell; Seu, Michelle; Zhang, Chi; Zhou, Zhengbing; Choi, Ji Suk; Jiang, Xuesong; Chen, Long; Walia, Gurjot; Yan, Jerry; Callanan, Megan; Liu, Huanhuan; Colbert, Kevin; Morrissette-McAlmon, Justin; Grayson, Warren; Reddy, Sashank; Sacks, Justin M.; Mao, Hai Quan.

In: Science translational medicine, Vol. 11, No. 490, eaau6210, 01.05.2019.

Research output: Contribution to journalArticle

Li, X, Cho, B, Martin, R, Seu, M, Zhang, C, Zhou, Z, Choi, JS, Jiang, X, Chen, L, Walia, G, Yan, J, Callanan, M, Liu, H, Colbert, K, Morrissette-McAlmon, J, Grayson, W, Reddy, S, Sacks, JM & Mao, HQ 2019, 'Nanofiber-hydrogel composite–mediated angiogenesis for soft tissue reconstruction', Science translational medicine, vol. 11, no. 490, eaau6210. https://doi.org/10.1126/scitranslmed.aau6210
Li, Xiaowei ; Cho, Brian ; Martin, Russell ; Seu, Michelle ; Zhang, Chi ; Zhou, Zhengbing ; Choi, Ji Suk ; Jiang, Xuesong ; Chen, Long ; Walia, Gurjot ; Yan, Jerry ; Callanan, Megan ; Liu, Huanhuan ; Colbert, Kevin ; Morrissette-McAlmon, Justin ; Grayson, Warren ; Reddy, Sashank ; Sacks, Justin M. ; Mao, Hai Quan. / Nanofiber-hydrogel composite–mediated angiogenesis for soft tissue reconstruction. In: Science translational medicine. 2019 ; Vol. 11, No. 490.
@article{fd8e1898e7184efa80eaa87b565b3ed9,
title = "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(-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.",
author = "Xiaowei Li and Brian Cho and Russell Martin and Michelle Seu and Chi Zhang and Zhengbing Zhou and Choi, {Ji Suk} and Xuesong Jiang and Long Chen and Gurjot Walia and Jerry Yan and Megan Callanan and Huanhuan Liu and Kevin Colbert and Justin Morrissette-McAlmon and Warren Grayson and Sashank Reddy and Sacks, {Justin M.} and Mao, {Hai Quan}",
year = "2019",
month = "5",
day = "1",
doi = "10.1126/scitranslmed.aau6210",
language = "English (US)",
volume = "11",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "490",

}

TY - JOUR

T1 - Nanofiber-hydrogel composite–mediated angiogenesis for soft tissue reconstruction

AU - Li, Xiaowei

AU - Cho, Brian

AU - Martin, Russell

AU - Seu, Michelle

AU - Zhang, Chi

AU - Zhou, Zhengbing

AU - Choi, Ji Suk

AU - Jiang, Xuesong

AU - Chen, Long

AU - Walia, Gurjot

AU - Yan, Jerry

AU - Callanan, Megan

AU - Liu, Huanhuan

AU - Colbert, Kevin

AU - Morrissette-McAlmon, Justin

AU - Grayson, Warren

AU - Reddy, Sashank

AU - Sacks, Justin M.

AU - Mao, Hai Quan

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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(-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.

AB - 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(-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.

UR - http://www.scopus.com/inward/record.url?scp=85065549441&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065549441&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.aau6210

DO - 10.1126/scitranslmed.aau6210

M3 - Article

C2 - 31043572

AN - SCOPUS:85065549441

VL - 11

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 490

M1 - eaau6210

ER -