Skip to content
BY-NC-ND 4.0 license Open Access Published by De Gruyter Open Access September 2, 2017

Using Electrospun Scaffolds to Promote Macrophage Phenotypic Modulation and Support Wound Healing

Katherine R. Hixon, Andrew J. Dunn, Reynaldo Flores, Benjamin A. Minden-Birkenmaier, Emily A. Growney Kalaf, Laurie P. Shornick and Scott A. Sell
From the journal Electrospinning


The development of pressure ulcers in spinal cord injury patients is extremely common, often requiring extensive surgical procedures. Macrophages (MACs) play a crucial role in the innate immune system, contributing to wound healing and overall regeneration. MACs have been found to possess the potential to be activated by external factors from their M0 inactive state to an M1 proinflammatory or M2 regenerative state. This study conducted a comprehensive evaluation of MAC phenotype in response to electrospun scaffolds of varying material fiber/pore diameter, fiber stiffness, and +/− inclusion of platelet-rich plasma (PRP). Generally, itwas found that the addition of PRP resulted in decreased pore size, where 5 silk fibroin (SF) had the stiffest fibers. Furthermore, PRP scaffolds demonstrated an increased production of VEGF and chemotaxis. The polycaprolactone (PCL) and SF scaffolds had the largest cell infiltration and proliferation. Overall, it was found that 5% SF had both ideal fiber and pore structure, allowing for cell infiltration further enhanced by the presence of PRP. Additionally, this scaffold led to a reasonable production of VEGF while still allowing fibroblast proliferation to occur. These results suggest that such a scaffold could provide an off-the-shelf product capable of modifying the local MAC response.


[1] Galli, S.J., N. Borregaard, and T.A. Wynn, Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol, 2011. 12(11): p. 1035-44.10.1038/ni.2109Search in Google Scholar PubMed PubMed Central

[2] Brown, B.N., et al.,Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component. Biomaterials, 2009. 30(8): p. 1482-91.10.1016/j.biomaterials.2008.11.040Search in Google Scholar PubMed PubMed Central

[3] Garg, K., et al., Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds. Biomaterials, 2013. 34(18): p. 4439-51.10.1016/j.biomaterials.2013.02.065Search in Google Scholar PubMed PubMed Central

[4] Martinez, F.O., et al., Macrophage activation and polarization. Front Biosci, 2008. 13: p. 453-61.10.2741/2692Search in Google Scholar PubMed

[5] Stout, R.D., et al., Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences. J Immunol, 2005. 175(1): p. 342-9.10.4049/jimmunol.175.1.342Search in Google Scholar PubMed

[6] Fairweather, D. and D. Cihakova, Alternatively activated macrophages in infection and autoimmunity. J Autoimmun, 2009. 33(3-4): p. 222-30.10.1016/j.jaut.2009.09.012Search in Google Scholar PubMed PubMed Central

[7] Bryant, R.A. and D.P. Nix, Acute&ChronicWounds: CurrentManagement Concepts. 4 ed. 2012, St. Louis, MO: Elsevier Mosby. 627.Search in Google Scholar

[8] Consortium for Spinal Cord Medicine Clinical Practice, G., Pressure ulcer prevention and treatment following spinal cord injury: a clinical practice guideline for health-care professionals. J Spinal Cord Med, 2001. 24 Suppl 1: p. S40-101.10.1080/10790268.2001.11753592Search in Google Scholar PubMed

[9] Garber, S.L. and D.H. Rintala, Pressure ulcers in veterans with spinal cord injury: a retrospective study. J Rehabil Res Dev, 2003. 40(5): p. 433-41.10.1682/JRRD.2003.09.0433Search in Google Scholar PubMed

[10] Gómez-Guillén, M.C., et al., Functional and bioactive properties of collagen and gelatin from alternative sources: A review. Food Hydrocolloids, 2011. 25(8): p. 1813-1827.10.1016/j.foodhyd.2011.02.007Search in Google Scholar

[11] Huang, C.-H., et al., Evaluation of proanthocyanidin-crosslinked electrospun gelatin nanofibers for drug delivering system. Ma terials Science and Engineering: C, 2012. 32(8): p. 2476-2483.10.1016/j.msec.2012.07.029Search in Google Scholar

[12] Dhandayuthapani, B., U.M. Krishnan, and S. Sethuraman, Fabrication and characterization of chitosan-gelatin blend nanofibers for skin tissue engineering. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2010. 94B(1): p. 264-272.10.1002/jbm.b.31651Search in Google Scholar PubMed

[13] Heydarkhan-Hagvall, S., et al., Three-dimensional electrospun ECM-based hybrid scaffolds for cardiovascular tissue engineering. Biomaterials, 2008. 29(19): p. 2907-2914.10.1016/j.biomaterials.2008.03.034Search in Google Scholar PubMed PubMed Central

[14] Woodruff, M.A. and D.W. Hutmacher, The return of a forgotten polymer-Polycaprolactone in the 21st century. Progress in Polymer Science, 2010. 35(10): p. 1217-1256.10.1016/j.progpolymsci.2010.04.002Search in Google Scholar

[15] Chen, H., et al., Electrospun chitosan-graft-poly ("- caprolactone)/poly ("-caprolactone) cationic nanofibrous mats as potential scaffolds for skin tissue engineering. International Journal of Biological Macromolecules, 2011. 48(1): p. 13-19.10.1016/j.ijbiomac.2010.09.019Search in Google Scholar PubMed

[16] Srinath, D., et al., Fibrous biodegradable l-alanine-based scaffolds for vascular tissue engineering. Journal of Tissue Engineering and Regenerative Medicine, 2014. 8(7): p. 578-588.Search in Google Scholar

[17] Ju, Y.M., et al., Bilayered scaffold for engineering cellularized blood vessels. Biomaterials, 2010. 31(15): p. 4313-4321.10.1016/j.biomaterials.2010.02.002Search in Google Scholar PubMed

[18] Daud, M.F.B., et al., An aligned 3D neuronal-glial co-culture model for peripheral nerve studies. Biomaterials, 2012. 33(25): p. 5901-5913.10.1016/j.biomaterials.2012.05.008Search in Google Scholar PubMed

[19] Meinel, L., et al., Silk implants for the healing of critical size bone defects. Bone, 2005. 37(5): p. 688-98.10.1016/j.bone.2005.06.010Search in Google Scholar PubMed

[20] Vepari, C. and D.L. Kaplan, Silk as a Biomaterial. Prog PolymSci, 2007. 32(8-9): p. 991-1007.10.1016/j.progpolymsci.2007.05.013Search in Google Scholar PubMed PubMed Central

[21] Zhang, F., et al., Preparation and characterization of electrospun silk fibroin nanofiber with addition of 1-ethyl-3-(3- dimethylarainopropyl) carbodiimide. Polymer Science Series A, 2011. 53(5): p. 397-402.10.1134/S0965545X1105004XSearch in Google Scholar

[22] Zhang, F., B. Zuo, and L. Bai, Study on the structure of SF fiber mats electrospun with HFIP and FA and cells behavior. Journal of Materials Science, 2009. 44(20): p. 5682-5687.10.1007/s10853-009-3800-5Search in Google Scholar

[23] Marelli, B., et al., Compliant electrospun silk fibroin tubes for small vessel bypass grafting. Acta Biomaterialia, 2010. 6(10): p. 4019-4026.10.1016/j.actbio.2010.05.008Search in Google Scholar PubMed

[24] Li, C., et al., Electrospun silk-BMP-2 scaffolds for bone tissue engineering. Biomaterials, 2006. 27(16): p. 3115-3124.10.1016/j.biomaterials.2006.01.022Search in Google Scholar PubMed

[25] Xu, S., et al., In vitro biocompatibility of electrospun silk fibroin mats with Schwann cells. Journal of Applied Polymer Science, 2011. 119(6): p. 3490-3494.10.1002/app.32996Search in Google Scholar

[26] Sheikh, F.A., et al., 3D electrospun silk fibroin nanofibers for fabrication of artificial skin. Nanomedicine: Nanotechnology, Biology and Medicine, 2015. 11(3): p. 681-691.10.1016/j.nano.2014.11.007Search in Google Scholar PubMed

[27] Chutipakdeevong, J., U.R. Ruktanonchai, and P. Supaphol, Process optimization of electrospun silk fibroin fiber mat for accelerated wound healing. Journal of Applied Polymer Science, 2013. 130(5): p. 3634-3644. 10.1002/app.39611Search in Google Scholar

[28] Anitua, E., et al., Effectiveness of autologous preparation rich in growth factors for the treatment of chronic cutaneous ulcers. J Biomed Mater Res B Appl Biomater, 2008. 84(2): p. 415-21.10.1002/jbm.b.30886Search in Google Scholar PubMed

[29] Sell, S.A., et al., A case report on the use of sustained release platelet-rich plasmafor the treatment of chronic pressure ulcers. J Spinal Cord Med, 2011. 34(1): p. 122-7.10.1179/107902610X12923394765616Search in Google Scholar PubMed PubMed Central

[30] Bernuzzi, G., et al., Platelet gel in the treatment of cutaneous ulcers: the experience of the Immunohaematology and Transfusion Centre of Parma. Blood Transfus, 2010. 8(4): p. 237-47.Search in Google Scholar

[31] El-Sharkawy, H., et al., Platelet-rich plasma: growth factors and pro- and anti-inflammatory properties. J Periodontol, 2007. 78(4): p. 661-9.10.1902/jop.2007.060302Search in Google Scholar PubMed

[32] Sell, S.A., et al., A Preliminary Study on the Potential ofManuka Honey and Platelet-Rich PlasmainWound Healing. International Journal of Biomaterials, 2012. 2012.10.1155/2012/313781Search in Google Scholar PubMed PubMed Central

[33] Sell, S.A., et al., Incorporating Platelet-Rich Plasma into Electrospun Scaffolds for Tissue Engineering Applications. Tissue Eng Part A, 2011. 17(21-22): p. 2723-37.10.1089/ten.tea.2010.0663Search in Google Scholar

[34] Dhurat, R. and M.S. Sukesh, Principles and Methods of Preparation of Platelet-Rich Plasma: A Review and Author’s Perspective. Journal of Cutaneous and Aesthetic Surgery, 2014. 7(4): p. 189-197.10.4103/0974-2077.150734Search in Google Scholar

[35] Pan, L., et al., Growth Factor Release from Lyophilized Porcine Platelet-Rich Plasma: Quantitative Analysis and Implications for Clinical Applications. Aesthetic Plast Surg, 2016. 40(1): p. 157-63.10.1007/s00266-015-0580-ySearch in Google Scholar

[36] Sell, S.A., et al., Cross-linking methods of electrospun fibrinogen scaffolds for tissue engineering applications. Biomed Mater, 2008. 3(4): p. 045001.10.1088/1748-6041/3/4/045001Search in Google Scholar

[37] Barnes, C.P., et al., Cross-linking electrospun type II collagen tissue engineering scaffolds with carbodiimide in ethanol. Tissue engineering, 2007. 13(7): p. 1593-1605.10.1089/ten.2006.0292Search in Google Scholar

[38] Deitzel, J.M., et al., The effect of processing variables on the morphology of electrospun nanofibers and textiles. Polymer, 2001. 42(1): p. 261-272.10.1016/S0032-3861(00)00250-0Search in Google Scholar

[39] Beachley, V. and X. Wen, Effect of electrospinning parameters on the nanofiber diameter and length. Materials science & engineering. C, Materials for biological applications, 2009. 29(3): p. 663-668.10.1016/j.msec.2008.10.037Search in Google Scholar PubMed PubMed Central

[40] Barnes, C.P., et al., Nanofiber technology: designing the next generation of tissue engineering scaffolds. Adv Drug Deliv Rev, 2007. 59(14): p. 1413-33.10.1016/j.addr.2007.04.022Search in Google Scholar PubMed

[41] Saino, E., et al., Effect of electrospun fiber diameter and alignment on macrophage activation and secretion of proinflammatory cytokines and chemokines. Biomacromolecules, 2011. 12(5): p. 1900-11.10.1021/bm200248hSearch in Google Scholar PubMed

[42] Shull, C.A. and S.P. Shull, Absorption ofMoisture by Gelatin in a Saturated Atmosphere. American Journal of Botany, 1920. 7(8): p. 318-326.10.1002/j.1537-2197.1920.tb05586.xSearch in Google Scholar

[43] Shan, Y.-H., et al., Silk fibroin/gelatin electrospun nanofibrous dressing functionalized with astragaloside IV induces healing and anti-scar effects on burn wound. International Journal of Pharmaceutics, 2015. 479(2): p. 291-301.10.1016/j.ijpharm.2014.12.067Search in Google Scholar PubMed

[44] Lawrence, B.D., et al., Effect of Hydration on Silk Film Material Properties.Macromolecular Bioscience, 2010. 10(4): p. 393-403.10.1002/mabi.200900294Search in Google Scholar PubMed PubMed Central

[45] Wu, J. and Y. Hong, Enhancing cell infiltration of electrospun fibrous scaffolds in tissue regeneration. Bioactive Materials.Search in Google Scholar

[46] Sell, S.A., et al., A case report on the use of sustained release platelet-rich plasmafor the treatment of chronic pressure ulcers. The Journal of Spinal Cord Medicine, 2011. 34(1): p. 122-127. 10.1179/107902610X12923394765616Search in Google Scholar PubMed PubMed Central

[47] Skotak, M., et al., Improved cellular infiltration into nanofibrous electrospun cross-linked gelatin scaffolds templated with micrometer sized polyethylene glycol fibers. Biomedical materials (Bristol, England), 2011. 6(5): p. 055012-055012.10.1088/1748-6041/6/5/055012Search in Google Scholar PubMed PubMed Central

[48] Balguid, A., et al., Tailoring fiber diameter in electrospun poly(epsilon-caprolactone) scaffolds for optimal cellular infiltration in cardiovascular tissue engineering. Tissue Eng Part A, 2009. 15(2): p. 437-44.10.1089/ten.tea.2007.0294Search in Google Scholar PubMed

[49] Bashur, C.A., M.J. Eagleton, and A. Ramamurthi, Impact of Electrospun Conduit Fiber Diameter and Enclosing Pouch Pore Size on Vascular Constructs Grown Within Rat Peritoneal Cavities. Tissue Engineering. Part A, 2013. 19(7-8): p. 809-823.10.1089/ten.tea.2012.0309Search in Google Scholar

[50] Planz, V., et al., Three-dimensional hierarchical cultivation of human skin cells on bio-adaptive hybrid fibers. Integr Biol (Camb), 2016. 8(7): p. 775-84.10.1039/C6IB00080KSearch in Google Scholar

Received: 2017-1-5
Accepted: 2017-5-25
Published Online: 2017-9-2
Published in Print: 2017-8-28

© 2017

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Scroll Up Arrow