Black Phosphorus Polymer Matrix Composites for Regenerative Medicine

Abstract

Black phosphorus (BP) is a two-dimensional (2D) material composed of multiple phosphorus atomic layers that interact via van der Waals interactions. Over the past years, BP has attracted significant attention in biomedical fields due to possessing degradability, biocompatibility, large surface area and strong near-infrared (NIR) absorption capacity. BP's degradability originates from its instability in the presence of an oxygenated aqueous environment, which can be degraded into non-toxic phosphate/phosphate species. Phosphate is a vital element in the body that contributes to the maintenance of nucleic acid, cellular membrane composition, activation of skin lipid mediator and bone mineralisation. The central hypothesis of this study was focused on developing a degradable system to encapsulate BP nanosheets to allow gradual degradation of BP and provide a controlled release of phosphate over time. It is hypothesised that the released phosphates from the polymer matrix can be further incorporated with calcium ions to help the formation of calcium phosphate for bone regeneration. Moreover, since phosphate plays an important role in angiogenesis and activation of skin lipid mediators, the NIR triggered phosphate release can be further investigated for skin cancer therapy. Many studies have investigated the potential application of polymer membranes incorporated with drugs and bioglass for potential guided bone regeneration. However, no study has been conducted on designing a degradable scaffold that provides a gradual and controlled release of phosphate supply to enhance bone osteogenesis. In this work, BP was incorporated into poly(lactic-co-glycolic acid) (PLGA) and silk fibroin (SF) via solution blow spinning (SBS) technique to investigate the effect of control release of BP from fibrous composites. The aim was to investigate the effect of the gradual release of phosphate species from the fibrous scaffolds on differentiation and mineralisation of Saos-2 (osteosarcoma cells) and MSC Y201 (immortalised stem cells). Raman spectroscopy, ICP/AES and SEM/EDS confirmed the successful incorporation of BP into the polymer fibre scaffolds. The BP/polymer fibre scaffolds successfully indicated a gradual release of phosphate/phosphate species into the aqueous solution over 8 weeks. The preliminary invitro results showed the concentration-dependent effect of BP on proliferation and mineralisation of Saos-2 and MSC Y201 cells. It was found that the higher concentration of BP (5 and 10 wt %) inhibited the cellular activity and mineralisation; however, the lower concentration of BP (0.5 and 1 wt %) showed a slight increase in cellular proliferation, and differentiation and mineralisation compared to the control polymer scaffolds. Therefore the 18 BP-based PLGA and SF fibre scaffolds may find future applications for guided bone regeneration by providing a gradual phosphate supply to enhance osteogenesis. Furthermore, the photoresponsive release behaviour of BP was investigated using near-infrared (NIR) radiation. Currently, cancer therapies mainly focus on the use of chemotherapy drugs and targeted drug deliveries that cause various side effects. Herein, the second hypothesis was focused on a new approach to employ BP as a phosphate supply for enhancing skin angiogenesis and also acting as photothermal agents under the NIR irradiation and helping ablation of cancerous skin cells without the use of drugs. For this purpose, the BP was incorporated into PLGA and SF microneedles via freeze-drying and vacuum drying techniques. It was found that the NIR irradiation caused a significant increase in temperature due to the strong optical absorption of BP, which triggered the phosphate release from polymer microneedles. Overall, the results reported here provide useful information about the applicable methods for incorporating 2D material into polymer structures, as well as providing an insight into the potential future application of BP for combined ph

Date of Award	1 Aug 2022
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Julie Gough (Supervisor), David Lewis (Supervisor) & Jonny Blaker (Supervisor)