18 TH INTERNATIONAL CONFERENCE ON COMPOSITE MATERIALS POLYMER-BASED COMPOSITE NANOFIBRES FOR WOUND HEALING APPLICATIONS V. Leung 1 , R. Hartwell 2 , H. Yang 1 , E. Rahmani-Neishaboor 2 , Y. Li 2 , F. Ko 1 *, A. Ghahary 2 1 Department of Materials Engineering, University of British Columbia, Vancouver, Canada 2 BC Professional Fire Fighters Burn & Wound Healing Lab., University of British Columbia, Vancouver, Canada * Corresponding author ( frank.ko@ubc.ca ) Keywords : nanofibres, wound healing, burn treatment, electrospinning 1 General Introduction to the injuries. Autografting has remained the golden standard for treatment of major wounds. In addition, skin replacement products such as Integra and other Materials play a significant role in defining injectable scaffolds have shown feasibility for partial functions for many products used today. Besides and full-thickness wounds. However, improvements finding suitable materials for specific applications, to current wound healing technology is required, as the focus of materials engineers is to manipulate autografting suffers from donor site morbidity, properties of given materials to suit these artificial skins like Integra requires multiple surgical applications. Examples include microstructural procedures, and injectable scaffolds lack mechanical engineering and materials alloying. Among those, integrity. the concept of combining desirable properties of different materials into composites has been used Electrospun nanofibres are recently throughout time. The field has grown exponentially introduced as mechanically robust scaffolds, and recently, with tremendous efforts towards have been shown effective in tissue regeneration due developing composites for increasingly specialized to its large surface area to volume ratio, ease of applications such as armor protection, aviation, fabrication, and capability as a drug encapsulation automotive, and energy. The attempt to utilize the matrix [4]. In addition, previous work on nanofibres full potential of composite materials is still ongoing, has demonstrated their superior cell regeneration with more recent attempts in developing active compared to other forms such as gel and foam [4, 5]. composites, such as shape memory and heat Building on the success of these earlier studies, our regulating materials. Another class of application on goal is to develop nanofibre-based systems that can which the composites community has been making manage the different wound healing processes for progress is bioactive materials, with typical example different types of wounds. The complexity of the being polymer composites for wound healing, which healing process and the dynamic nature of the body is greatly beneficial due to the intricate process require composite materials to achieve multiple involved. objectives associated with wound healing. Recently, the need for composite material designs in wound Indeed, the wound care sector is one of the healing has been outlined in the work by Rahmani- most advanced in biomedical industry, with a Neishaboor et al. who produced a composite worldwide market worth of $13 billion (2008) [1]. microsphere system containing poly(lactic-glycolic The massive demand on wound care comes from acid) (PLGA) and chitosan conjugated with stratafin patients of both acute and chronic wounds. There are [6], in which the chitosan provides drug binding nearly 500,000 burn patients annually in the US ability and the PLGA provides protection against requiring treatment [2], with 6 million patients in the burst release of the drug. The work by Rahmani- US suffering from chronic wounds [3]. In addition, Neishaboor et al. demonstrated that via composite 120,000 surgical procedures, which create wounds, designs, wound care products can become are performed daily. Advanced wound healing multifunctional. The focus of our study is therefore technologies are beneficial in reducing the burden on to manipulate properties of nanofibre wound healthcare systems worldwide, which stems from the dressings through composite designs in order cost of medical care and loss of productivity linked
regulate the wound healing process while providing 2 Materials and Methods the necessary protection. 2.1 Materials and Preparation Our focus on wound healing management is PCL and PVA, 98-99% hydrolyzed, was purchased on controlling the release rate of therapeutic from Sigma Aldrich. Dichloromethane (DCM) and elements, and scaffold mechanical properties. The dimethylformamide (DMF), at a weight ratio of 1:1, specific target for release and mechanical properties were used to dissolve PCL (8 – 12 wt%) for the for depend on the type of wound and drugs considered. the outer shell of the sandwich structured scaffold. For example, a fresh wound may require a relatively All solvents in this study were purchased from quick release of antibiotics, whereas an Fisher Scientific. Distilled water was used to epithelialized wound may require a more sustainable dissolve PVA (8 – 12 wt%) for the inner layer of the release of drugs for improving wound healing. scaffold. Aqueous sodium tetraborate solutions were Examples of release profiles for dressings for several also prepared for crosslinking reactions with PVA. types of wound are shown in Figure 1 . It must be 2.2 Electrospinning noted that in reality the optimal release profile depend greatly on the drug and patient condition, but Polymer solutions were loaded into 10mL syringes the generalized profiles in Figure 1 can nonetheless with 20G1 needles (B-D). Electrospinning was provide a starting objective for our study. performed using the Katotech nanofibre electrospinning unit at an applied voltage of 18 – 22 kV and a solution flow rate of 0.3 – 0.5 mL/hr. Nanofibres were collected on a stationary drum. Sandwich scaffold were prepared by first electrospinning a layer of PCL with thickness varying from 200 - 400µm, followed by a PVA layer and then a PCL layer of the same thickness as the first layer. In order to enhance the structural integrity of PVA fibres in aqueous environments, crosslinking was performed by spraying sodium tetraborate solutions onto the fibers after electrospinning of the PVA layer. It is also anticipated that crosslinking the PVA layer can further help control drug release from the fiber. 2.3 Optical Characterization Figure 1: Examples of release profiles for different wounds (adopted from [7]) Nanofibre morphology was observed via a Hitachi S-3000N scanning electron microscope (SEM). The Materials play a significant role in both wound sandwich composite structure was observed in 3D healing management and mechanical properties of using an Olympus LEXT 4000 laser confocal the dressing. In our study, the importance of microscope. Images taken from SEM and confocal materials for wound healing is demonstrated by a microscope were analyzed for fibre diameter, composite scaffold containing electrospun diameter distribution, and layer thickness using the polycaprolactone (PCL) and polyvinyl alcohol software ImageJ. (PVA). A sandwich structured scaffold is 2.4 Mechanical Characterization considered, in which drug-loaded PVA is the protected by PCL outer shells in a layered Uniaxial tensile tests were performed on the organization. The drug release and mechanical composite nanofibres as well as nanofibres of properties of the composite, as well as methods for individual polymers using a Katotech KES-G1 controlling these properties are assessed. tensile tester with a strain rate of 0.1 cm/s. The average ultimate tensile strengths and strains were
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