Tissue Engineering of Axially Vascularized Soft-Tissue Flaps with a Poly-(ɛ-Caprolactone) Nanofiber-Hydrogel Composite

Henn, Dominic; Chen, Kellen; Fischer, Katharina S.; Rauh, Annika; Barrera, Janos A.; Kim, Yoo Jin; Martin, Russell; Hannig, Matthias; Niedoba, Patricia; Reddy, Sashank K.; Mao, Hai Quan; Kneser, Ulrich; Gurtner, Geoffrey C.; Sacks, Justin M.

doi:10.1089/wound.2019.0975

Cited by 11 publications

(14 citation statements)

References 33 publications

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“…4,18 Also, it should not elicit an inflammatory or immune response and be well tolerated by the recipient organism. 22,[31][32][33] Other qualities may also be desirable in the context of human application, such as relatively short production times, minimal surgical intervention, and a low complication rate. Unfortunately, no perfect method exists yet.…”

Section: Discussionmentioning

confidence: 99%

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Techniques and Innovations in Flap Engineering: A Review

Kouniavski

Egozi

Wolf

2022

Plastic and Reconstructive Surgery - Global Open

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Background: Currently, the gold standard for complex defect reconstruction is autologous tissue flaps, with vascularized composite allografts as its highest level. Good clinical results are obtained despite considerable obstacles, such as limited donor sites, donor site morbidity, and complex operations. Researchers in the field of tissue engineering are trying to generate novel tissue flaps requiring small or no donor site sacrifice. At the base of existing technologies is the tissue’s potential for regeneration and neovascularization. Methods: A review was conducted identifying relevant published articles in PubMed on the subject of flap engineering, with the focus on plastic surgery. This review article surveys contemporary technologies in flap engineering, including cell sheet technology, prefabricated flaps, and tissue engineering chambers. Conclusions: Some of the described procedures, though not yet ready for clinical use, are certainly ready for trial in large animal models and even human studies. Tissue engineering is a promising field for the handling of large and complex tissue defects.

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Section: Discussionmentioning

confidence: 99%

“…As there is no extrinsic vascular supply to ECM scaffolds, large defects cannot be covered and inner vascular supply is needed. Henn et al 32 implanted previously described NHCs into isolation chambers in vivo, together with an AV loop. This study proved the feasibility of creating an axial tissue flap using an injectable scaffold.…”

Section: Hydrogelsmentioning

confidence: 99%

Techniques and Innovations in Flap Engineering: A Review

Kouniavski

Egozi

Wolf

2022

Plastic and Reconstructive Surgery - Global Open

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“…Plastic and Reconstructive Surgery • March 2022 we used the arteriovenous loop model, which was first described by Melvin Spira's group in 1979 and has since been developed into a standard model for the investigation of blood vessel development in vivo without the need for externally applied growth factors. 13,[27][28][29] Enrichment of nanofiber hydrogel composite with fractionated fat led to a significantly stronger vascularization compared to nanofiber hydrogel composite alone and maintained its shape without shrinking over 21 days of in vivo implantation. In nanofiber hydrogel composite with fractionated fat-remodeled tissue, functional ink-perfused blood vessels were evenly distributed and reached the periphery of the tissue, whereas blood vessels in the periphery of nanofiber hydrogel composite tissue without fractionated fat were sparse.…”

Section: Ementioning

confidence: 99%

“…This nanofiber hydrogel compound displays biomechanical properties similar to adipose tissue, and has also been proven to enable a durable volume restoration. 10,11 Moreover, the nanofiber hydrogel compound enhances native tissue regeneration and promotes angiogenesis in vivo, thus providing an alternative approach for minimally invasive defect reconstruction without the risk for donor-site morbidity. 10,11…”

mentioning

confidence: 99%

Enrichment of Nanofiber Hydrogel Composite with Fractionated Fat Promotes Regenerative Macrophage Polarization and Vascularization for Soft-Tissue Engineering

Henn

Fischer

Chen

et al. 2022

Plastic &Amp; Reconstructive Surgery

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Background: Fractionated fat has been shown to promote dermal regeneration; however, the use of fat grafting for reconstruction of soft-tissue defects is limited because of volume loss over time. The authors have developed a novel approach for engineering of vascularized soft tissue using an injectable nanofiber hydrogel composite enriched with fractionated fat. Methods: Fractionated fat was generated by emulsification of groin fat pads from rats and mixed in a 3:1 ratio with nanofiber hydrogel composite (nanofiber hydrogel composite with fractionated fat). Nanofiber hydrogel composite with fractionated fat or nanofiber hydrogel composite alone was placed into isolation chambers together with arteriovenous loops, which were subcutaneously implanted into the groin of rats (n = 8 per group). After 21 days, animals were euthanized and systemically perfused with ink, and tissue was explanted for histologic analysis. Immunofluorescent staining and confocal laser scanning microscopy were used to quantify CD34+ progenitor cell and macrophage subpopulations. Results: Nanofiber hydrogel composite with fractionated fat tissue maintained its shape without shrinking and showed a significantly stronger functional vascularization compared to composite alone after 21 days of implantation (mean vessel count, 833.5 ± 206.1 versus 296.5 ± 114.1; p = 0.04). Tissue heterogeneity and cell count were greater in composite with fractionated fat (mean cell count, 49,707 ± 18,491 versus 9263 ± 3790; p = 0.005), with a significantly higher number of progenitor cells and regenerative CD163+ macrophages compared to composite alone. Conclusions: Fractionated fat–enriched nanofiber hydrogel composite transforms into highly vascularized soft tissue over 21 days without signs of shrinking and promotes macrophage polarization toward regenerative phenotypes. Enrichment of injectable nanofiber hydrogel composite with fractionated fat represents a promising approach for durable reconstruction of soft-tissue defects. Clinical Relevance Statement: The authors' approach for tissue engineering may ultimately lay the groundwork for clinically relevant applications with the goal of generating large volumes of vascularized soft tissue for defect reconstruction without donor site morbidity.

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“…12 They are effective for adipocyte proliferation and migration 15 as well as for the production of AT substitutes in vitro and in vivo when used with adipogenic stimulants. 114,121 Thus, AT related studies conducted with different synthetic scaffolds such as poly(caprolactone) (PCL), 147 poly(ethylene glycol) (PEG) and derivatives, 122,123 and poly(ethylene terephthalate) (PET) 124 can be found in the literature. The synthetic polymers allowing the generation of vasculature formation in AT engineering studies are briefly discussed below.…”

Section: Materials For Vascularized Adipose Tissue Reconstructionmentioning

confidence: 99%