Amine-Reactive Augmentation of Silk Fibroin Mats for Increasing Cargo Retention Capabilities
Source abstract
Abstract
Silk fibroin (SF) is an ideal biomaterial for next-generation clinical wound dressings due to its biocompatibility and tunable mechanical properties. Cell therapies for wound healing have explored using SF as the base for delivering beneficial cargo; however, retention is poor due to exudate “wash out.” To address concerns with the premature release of cargo from SF-fabricated wound dressings, we utilized amine-reactive chemistry to conjugate SF mats with azido-reactive dibenzocyclooctyne (DBCO) that can then attach complementary azido-tagged cargo through chemoselective immobilization. SF mats were made using electrospinning of a 1:1 SF/PCL solution and were then conjugated with N-Hydroxysuccinimide-dibenzocyclooctyne ester (DBCO). PBS soaking was used for control SF mats. SF mats were then imaged and characterized using the following metrics: pore size, fiber alignment, fiber distribution, fiber diameter, ultimate tensile strength, tangent modulus, proteolytic degradation, absorption, and retention. Successful DBCO conjugation of SF mats was confirmed through the presence of the Az-Cy5 dye while exhibiting no significant changes to the DBCO SF mats in any of the tested metrics compared to controls. Our results provide evidence that the amine chemistry responsible for the DBCO conjugation does not alter important SF mat properties. This confirms that DBCO augmentation paired with Az-Cy5 tags may be a viable approach for immobilizing different therapeutic cargoes to aid wound healing efforts.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Silk-based biomaterials and applications · Wound Healing and Treatments · Electrospun Nanofibers in Biomedical Applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, 4200 Fifth Avenue, Pittsburgh, PA 15260, USA
Department of Surgery, School of Medicine, University of Pittsburgh, UPMC Presbyterian Hospital, F1281 200 Lothrop Street, Pittsburgh, PA 15213, USA
Department of Biomedical Engineering, College of Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA
Department of Mechanical Engineering, College of Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA
Department of Mechanical and Materials Engineering, Swanson School of Engineering, University of Pittsburgh, 4200 Fifth Avenue, Pittsburgh, PA 15260, USA
Department of Chemical and Petroleum Engineering, Swanson School of Engineering, University of Pittsburgh, 4200 Fifth Avenue, Pittsburgh, PA 15260, USA
Center for Vascular Remodeling and Regeneration, University of Pittsburgh, 4200 Fifth Avenue, Pittsburgh, PA 15260, USA
Department of Cardiothoracic Surgery, School of Medicine, University of Pittsburgh, 4401 Penn Avenue, Central Plant Building, Suite 3200, Pittsburgh, PA 15224, USA
Clinical and Translational Sciences Institute, School of Medicine, University of Pittsburgh, Forbes Tower, Meyran Avenue Suite 7057, Pittsburgh, PA 15213, USA
McGowan Institute for Regenerative Medicine, School of Medicine, University of Pittsburgh, 450 Technology Drive, Pittsburgh, PA 15219, USA
Magee-Womens Research Institute, School of Medicine, University of Pittsburgh, 204 Craft Avenuee, Pittsburgh, PA 15213, USA
Department of Pathology, School of Medicine, University of Pittsburgh, S-417 BST 200 Lothrop Street, Pittsburgh, PA 15261, USA
Funding
University of Pittsburgh · National Institutes of Health
References (51)
Show source-provided references
1. Human Wounds and Its Burden: An Updated Compendium of Estimates10.1089/wound.2019.0946 ↗
2. Dong, Y., and Wang, Z. (2023). ROS-scavenging materials for skin wound healing: Advancements and applications. Front. Bioeng. Biotechnol., 11.10.3389/fbioe.2023.1304835 ↗
3. Reactive oxygen species (ROS) and wound healing: The functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process10.1111/iwj.12557 ↗
4. bFGF Promotes the Migration of Human Dermal Fibroblasts under Diabetic Conditions through Reactive Oxygen Species Production via the PI3K/Akt-Rac1- JNK Pathways10.7150/ijbs.11921 ↗
5. Delayed wound healing in diabetic (db/db) mice with Pseudomonas aeruginosa biofilm challenge: A model for the study of chronic wounds10.1111/j.1524-475X.2010.00608.x ↗
6. Vecin, N.M., and Kirsner, R.S. (2023). Skin substitutes as treatment for chronic wounds: Current and future directions. Front. Med., 10.10.3389/fmed.2023.1154567 ↗
7. Design Considerations, Formulation Approaches, and Strategic Advances of Hydrogel Dressings for Chronic Wound Management10.1021/acsomega.2c06806 ↗
8. Epithelialization in Wound Healing: A Comprehensive Review10.1089/wound.2013.0473 ↗
9. Emerging treatment strategies in wound care10.1111/iwj.13786 ↗
10. Moist Wound Healing with Commonly Available Dressings10.1089/wound.2020.1232 ↗
11. Wound Dressings: Selecting the Most Appropriate Type10.1007/s40257-013-0046-4 ↗
12. An overview of electrospun membranes loaded with bioactive molecules for improving the wound healing process10.1016/j.ejpb.2019.03.010 ↗
13. Green electrospun Manuka honey/silk fibroin fibrous matrices as potential wound dressing10.1016/j.matdes.2017.01.023 ↗
14. The effect of a new wound dressing on wound healing: Biochemical and histopathological evaluation10.1016/j.burns.2019.02.013 ↗
15. Silk fibroin and silk-based biomaterial derivatives for ideal wound dressings10.1016/j.ijbiomac.2020.08.041 ↗
16. Challenges and innovations in treating chronic and acute wound infections: From basic science to clinical practice10.1093/burnst/tkac014 ↗
17. Silk-Based Biomaterials in Cutaneous Wound Healing: A Systematic Review10.1097/01.ASW.0000546233.35130.a9 ↗
18. Silk Fibroin and Its Nanocomposites for Wound Care: A Comprehensive Review10.1021/acspolymersau.3c00050 ↗
19. Overview of Silk Fibroin Use in Wound Dressings10.1016/j.tibtech.2018.04.004 ↗
20. PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing10.1111/j.1524-475X.2008.00410.x ↗
21. TGF-β1 Accelerates Wound Healing: Reversal of Steroid-Impaired Healing in Rats and Rabbits10.3109/08977199109000293 ↗
22. Animal models in burn research10.1007/s00018-014-1612-5 ↗
23. Fibroblasts and myofibroblasts in wound healing
24. Johnson, B.Z., Stevenson, A.W., Prêle, C.M., Fear, M.W., and Wood, F.M. (2020). The Role of IL-6 in Skin Fibrosis and Cutaneous Wound Healing. Biomedicines, 8.10.3390/biomedicines8050101 ↗
25. Epithelial mesenchymal transition traits in honey-driven keratinocyte wound healing: Comparison among different honeys10.1111/j.1524-475X.2012.00825.x ↗
26. Extracellular vesicles modulate key signalling pathways in refractory wound healing10.1093/burnst/tkad039 ↗
27. Engineering pro-angiogenic biomaterials via chemoselective extracellular vesicle immobilization10.1016/j.biomaterials.2021.121357 ↗
28. Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization10.1186/s13287-020-01937-8 ↗
29. Stem Cell-Derived Extracellular Vesicles as Immunomodulatory Therapeutics10.1155/2019/5126156 ↗
30. Stem cell derived extracellular vesicles for vascular elastic matrix regenerative repair10.1016/j.actbio.2020.07.002 ↗
31. Extracellular vesicle-based therapeutics for the regeneration of chronic wounds: Current knowledge and future perspectives10.1016/j.actbio.2020.11.001 ↗
32. Klyachko, N.L., Arzt, C.J., Li, S.M., Gololobova, O.A., and Batrakova, E.V. (2020). Extracellular Vesicle-Based Therapeutics: Preclinical and Clinical Investigations. Pharmaceutics, 12.10.3390/pharmaceutics12121171 ↗
33. Metabolic glycan labeling and chemoselective functionalization of native biomaterials10.1016/j.biomaterials.2018.08.012 ↗
34. Teramoto, H., Shirakawa, M., and Tamada, Y. (2020). Click Decoration of Bombyx mori Silk Fibroin for Cell Adhesion Control. Molecules, 25.10.3390/molecules25184106 ↗
35. Bioresorbable silk grafts for small diameter vascular tissue engineering applications: In vitro and in vivo functional analysis10.1016/j.actbio.2020.01.020 ↗
36. A custom image-based analysis tool for quantifying elastin and collagen micro-architecture in the wall of the human aorta from multi-photon microscopy10.1016/j.jbiomech.2014.01.027 ↗
37. Electrospinning based biomaterials for biomimetic fabrication, bioactive protein delivery and wound regenerative repair10.1093/rb/rbae139 ↗
38. Green electrospun grape seed extract-loaded silk fibroin nanofibrous mats with excellent cytocompatibility and antioxidant effect10.1016/j.colsurfb.2015.12.001 ↗
39. Shi, Q., Qian, Z., Liu, D., Sun, J., Wang, X., Liu, H., Xu, J., and Guo, X. (2017). GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model. Front. Physiol., 8.10.3389/fphys.2017.00904 ↗
40. Surface modification of Thai silk fibroin scaffolds with gelatin and chitooligosaccharide for enhanced osteogenic differentiation of bone marrow-derived mesenchymal stem cells10.1002/jbm.b.32802 ↗
41. Genetic Code Expansion of the Silkworm Bombyx mori to Functionalize Silk Fiber10.1021/acssynbio.7b00437 ↗
42. Biodegradation of Silk Biomaterials10.3390/ijms10041514 ↗
43. Degradation Mechanism and Control of Silk Fibroin10.1021/bm101422j ↗
44. Enzymatic degradation behavior of porous silk fibroin sheets10.1016/S0142-9612(02)00326-5 ↗
45. Enzymatic Degradation of Bombyx mori Silk Materials: A Review10.1021/acs.biomac.0c00090 ↗
46. Grabska-Zielińska, S., and Sionkowska, A. (2021). How to Improve Physico-Chemical Properties of Silk Fibroin Materials for Biomedical Applications?—Blending and Cross-Linking of Silk Fibroin—A Review. Materials, 14.10.3390/ma14061510 ↗
47. Anti-inflammatory and M2 macrophage polarization-promoting effect of mesenchymal stem cell-derived exosomes10.1016/j.intimp.2021.107823 ↗
48. MSC-Derived Extracellular Vesicles to Heal Diabetic Wounds: A Systematic Review and Meta-Analysis of Preclinical Animal Studies10.1007/s12015-021-10164-4 ↗
49. The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: A comprehensive review10.1186/s13287-021-02697-9 ↗
50. Revolutionizing dermatology: Harnessing mesenchymal stem/stromal cells and exosomes in 3D platform for skin regeneration10.1007/s00403-024-03055-4 ↗
51. Bray, E.R., Oropallo, A.R., Grande, D.A., Kirsner, R.S., and Badiavas, E.V. (2021). Extracellular Vesicles as Therapeutic Tools for the Treatment of Chronic Wounds. Pharmaceutics, 13.10.3390/pharmaceutics13101543 ↗