In vivo evaluation of an electrospun and 3D printed cellular delivery device for dermal wound healing
Ryan M. Clohessy
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia
Search for more papers by this authorDavid J. Cohen
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia
Search for more papers by this authorKarolina Stumbraite
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia
Search for more papers by this authorCorresponding Author
Barbara D. Boyan
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia
Correspondence
Barbara D. Boyan, College of Engineering, Virginia Commonwealth University, 601 West Main Street, Richmond, VA 23284.
Email: bboyan@vcu.edu
Search for more papers by this authorZvi Schwartz
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia
Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas
Search for more papers by this authorRyan M. Clohessy
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia
Search for more papers by this authorDavid J. Cohen
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia
Search for more papers by this authorKarolina Stumbraite
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia
Search for more papers by this authorCorresponding Author
Barbara D. Boyan
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia
Correspondence
Barbara D. Boyan, College of Engineering, Virginia Commonwealth University, 601 West Main Street, Richmond, VA 23284.
Email: bboyan@vcu.edu
Search for more papers by this authorZvi Schwartz
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia
Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas
Search for more papers by this authorFunding information: U.S. Department of Defense, Grant/Award Number: W81XWH-11-1-0306
Abstract
Burns and chronic wounds are especially challenging wounds to heal. In efforts to heal these wounds, physicians often use autologous skin grafts to help restore mechanical and barrier functionality to the wound area. These grafts are, by nature, limited in availability. In an effort to provide an alternative, we have developed an electrospun wound dressing designed to incorporate into the wound with the option to deliver a cellular payload. Here, a blend of poly(glycolic acid) and poly(ethylene glycol) was electrospun as part of a custom fabrication method that incorporated 3D printed poly(vinyl alcohol) sacrificial elements. This preparation is unique compared to traditional electrospinning as sacrificial elements provide an internal void space for an injectable payload to be delivered to the wound site. When the construct was tested in vivo (full thickness excisional skin wounds), wound closure was slightly delayed by the presence of the scaffold in both normal and challenged wounds. Quality of healing was improved in normal wounds as measured by histomorphometrics when treated with the construct and exhibited increased neovascularization. Our results demonstrate that the extracellular matrix-like scaffold developed in this study is beneficial to healing of full thickness skin defects and may benefit challenged wounds.
REFERENCES
- Altavilla, D., Saitta, A., Cucinotta, D., Galeano, M., Deodato, B., Colonna, M., … Sqadrito, F. (2001). Inhibition of lipid peroxidation restores impaired vascular endothelial growth factor expression and stimulates wound healing and angiogenesis in the genetically diabetic mouse. Diabetes, 50(3), 667–674.
- Bonfield, W. (2006). Designing porous scaffolds for tissue engineering. Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences, 364(1838), 227–232.
- Bonvalle, P. P., Schultz, M. J., Mitchell, E. H., Bain, J. L., Culpepper, B. K., Thomal, S. J., & Bellis, S. L. (2015). Microporous dermal0mimetic electrospun scaffolds pre-seeded with fibroblasts promote tissue regeneration in full-thickness skin wounds. PLoS One, 10(3), e0122359.
- Boomer, L., Liu, Y., Mahler, N., Johnson, J., Zak, K., Nelson, T., … Besner, G. E. (2014). Scaffolding for challenging environments: Materials selection for tissue engineered intestine. Journal of Biomedical Materials Research: Part A, 102(11), 3795–3802.
- Ding, J., Kwan, P., Ma, Z., Iwashina, T., Wang, J., Shankowsky, H. A., & Tredget, E. E. (2016). Synergistic effect of vitamin D and low concentration of transforming growth factor beta 1, a potential role in dermal wound healing. Burns, 42(6), 1277–1286.
- Drewa, T., Galazka, P., Prokurat, A., Wolski, Z., Sir, J., Wysocka, K., & Czajkowski, R. (2005). Abdominal wall repair using a biodegradable scaffold seeded with cells. Journal of Pediatric Surgery, 40(2), 317–321.
- Eweida, A. M., & Marei, M. K. (2015). Naturally occurring extracellular matrix scaffolds for dermal regeneration: Do they really need cells? BioMed Research International, 2015, 839694.
- Fu, K., Pack, D. W., Kilbanov, A. M., & Langer, R. (2000). Visual evidence of acidic environment within degrading poly(lactic-co-glycolic acid) (PLGA) microspheres. Pharmaceutical Research, 17(1), 100–106.
- Fu, Q., Deng, C. L., Zhao, R. Y., Wang, Y., & Cao, Y. (2014). The effect of mechanical extension stimulation combined with epithelial cell sorting on outcomes of implanted tissue-engineered muscular urethras. Biomaterials, 35(1), 105–112.
- Harding, K. G., Morris, H. L., & Patel, G. K. (2002). Science, medicine and the future: Healing chronic wounds. BMJ. 2002 Jan 19; 324(7330): 160–3.
- Jimi, S., De Francesco, F., Ferraro, G. A., Riccio, M., & Hara, S. (2016). A novel skin splint for accurately mapping dermal Remodeling and epithelialization during wound healing. Journal of Cellular Physiology 2017 Jun; 232(6): 1225–1232.
- Johnson, T., Bahrampourian, R., Patel, A., & Mequanint, K. (2010). Fabrication of highly porous tissue-engineering scaffolds using selective spherical porogens. Bio-medical Materials and Engineering, 20(2), 107–118.
- Kato, Y., Ozawa, S., Miyamoto, C., Maehata, Y., Suzuki, A., Maeda, T., & Baba, Y. (2013). Acidic extracellular microenvironment and cancer. Cancer Cell International, 13(1), 89.
- Kumar, P. (2008). Classification of skin substitutes. Burns, 34(1), 148–149.
- Lee, C. S., Burnsed, O. A., Raghuram, V., Kalisvaart, J., Boyan, B. D., & Schwartz, Z. (2012). Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration. Stem Cell Research & Therapy, 3(4), 35.
- Lemo, N., Marignac, G., Reyes-Gomes, E., Lilin, T., Crosaz, O., Ehrenfest, D.M. (2010). Cutaneous reepithelialization and wound contraction after skin biopsies in rabbits: a mathematical model for healing and remodelling index. Veterinarski Arhiv, 80(5), 637–652
- Leslie, S. K., Cohen, D. J., Sedlaczek, J., Pinsker, E. J., Boyan, B. D., & Schwartz, Z. (2013). Controlled release of rat adipose-derived stem cells from alginate microbeads. Biomaterials, 34(33), 8172–8184.
- Li, C. Y., & Hu Mh, H. J. J. (2019). Use of aligned microscale sacrificial fibers in creating biomimetic, anisotropic poly(glycerol sebacate) scaffolds. Polymers, 11(9), 1492–1508.
- Li, W. J., Laurencin, C. T., Caterson, E. J., Tuan, R. S., & Ko, F. K. (2002). Electrospun nanofibrous structure: A novel scaffold for tissue engineering. Journal of Biomedical Materials Research, 60(4), 613–621.
- Lin, H. R., Kuo, C. J., Yang, C. Y., Shaw, S. Y., & Wu, Y. J. (2002). Preparation of macroporous biodegradable PLGA scaffolds for cell attachment with the use of mixed salts as porogen additives. Journal of Biomedical Materials Research, 63(3), 271–279.
- Liu, S., Zhang, H., Zhang, X., Lu, W., Huang, X., Xie, H., … Jin, Y. (2011). Synergistic angiogenesis promoting effects of extracellular matrix scaffolds and adipose-derived stem cells during wound repair. Tissue Engineering. Part A, 17(5–6), 725–739.
- Maxson, S., Lopex, E. A., Yoo, D., Danilkovitch-Miagkova, A., & Leroux, M. A. (2012). Concise review: Role of mesenchymal stem cells in wound repair. Stem Cells Translational Medicine, 1(2), 142–149.
- Nuutila, K., Singh, M., Kruse, C., Philip, J., Caterson, E. J., & Eriksson, E. (2016). Titanium wound chambers for wound healing research. Wound Repair and Regeneration, 24(6), 1097–1102.
- O'Meara, S., Cullum, N., Majid, M., & Sheldon, T. (2000). Systematic reviews of wound care management: (3) antimicrobial agents for chronic wounds; (4) diabetic foot ulceration. Health Technology Assessment, 4(21), 1–237.
- D. P. Orgill, & C. Blanco (Eds.). (2009). Biomaterials for treating skin loss. Sawston, Cambridge, UK: Woodhead Publishing.
- Rowan, M. P., Cancio, L. C., Elster, E. A., Burmeister, D. M., Rose, L. F., Natesan, S., … Chung, K. K. (2015). Burn wound healing and treatment: Review and advancements. Critical Care, 19, 243.
- Sadeghi, A. R., Nokhasteh, S., Molavi, A. M., Khorsand-Ghayeni, M., Naderi-Meshkin, H., & Mahdizadeh, A. (2016). Surface nodification of electrospun PLGA scaffold with collagen for bioengineered skin substitutes. Materials Science & Engineering. C, Materials for Biological Applications, 66, 130–137.
- Scharstuhl, A., Mutsaers, H. A., Pennings, S. W., Szark, W. A., Russel, F. G., & Wagener, F. A. (2009). Curcumin-induced fibroblast apoptosis and in vitro wound contraction are regulated by antioxidants and heme oxygenase: Implications for scar formation. Journal of Cellular and Molecular Medicine, 13(4), 712–725.
- Sen, C. K., Gordillo, G. M., Roy, S., Kirsner, R., Lambert, L., Hunt, T. K., … Longaker, M. T. (2009). Human skin wounds: A major and snowballing threat to public health and the economy. Wound Repair and Regeneration, 17(6), 763–771.
- Shores, J. R., Gabriel, A., & Gupta, S. (2007). Skin substitutes and alternatives: A review. Advances in Skin & Wound Care, 20(9 Pt 1), 493–508.
- Smith, O. J., Edmondson, S. J., Bystrzonowski, N., Hachach-Haram, N., Kanapathy, M., Richards, T., & Mosahebi, A. (2016). The CelluTome epidermal graft-harvesting system: A patient-reported outcome measure and cost evaluation study. International Wound Journal. 2017 Jun; 14(3): 555–560.
- Sullivan, T. P., Eaglstein, W. H., Davis, S. C., & Mertz, P. (2001). The pig as amodel for human wound healing. Wound Repair and Regeneration, 9(2), 66–76.
- Trujillo, A. N., Kesl, S. L., Sherwood, J., Wu, M., & Gould, L. J. (2015). Demonstration of the rat ischemic skin wound model. Journal of Visualized Experiments, 98, e52637.
- Wang, X., Ge, J., Tredget, E. E., & Wu, Y. (2014). The mouse excisional wound splinting model, including applications for stem cell transplantation. Nature Protocols, 8(2), 302–309.
- Xie, S. Y., Peng, L. H., Shan, Y. H., Niu, J., Xiong, J., & Gao, J. Q. (2016). Adult stem cells seeded on electrospinning silk fibroin Nanofibrous scaffold enhance wound repair and regeneration. Journal of Nanoscience and Nanotechnology, 16(6), 5498–5505.
