Poly(caprolactone)/lignin-based 3D-printed dressings loaded with a novel combination of bioactive agents for wound-healing applications
Curcumin (CUR) has been shown to possess significant anti-inflammatory properties and significant wound healing potential. Additionally, lignin (LIG) is a renewable biomacromolecule with well-known antioxidant and antimicrobial properties, which makes this biomacromolecule a good candidate to be included in medical materials, such as wound dressings. Although many of the wound dressings used at present have interesting features, some are limited in terms of antibacterial properties. To address these limitations, in the present work, both CUR and LIG were combined with poly(caprolactone) (PCL), a biocompatible polymer, to obtain dressings with antioxidant and antimicrobial properties for wound healing treatment. Moreover, D-Panthenol (DPA) was included in the composite materials formulation due to its skin regenerative ability by enhancing epidermal differentiation.
Semi-solid extrusion (SSE) 3D printing was used to manufacture wound dressings without the use of any solvents. 3D-printed dressings provided a sustained DPA and CUR release for periods of up to 4 and 35 days, respectively. A DPPH (2,2-diphenyl-1-picrylhydrozyl) assay was performed confirming that the presence of LIG and CUR provided antioxidant properties to the 3D-printed dressings.
Highlights
- 3D printing was used to prepare PCL/lignin-based wound dressings loaded with curcumin and D-Panthenol.
- The resulting 3D-printed dressings showed excellent antioxidant and antimicrobial properties.
- 3D-printed dressings provided sustained release of both bioactive agents, D-Panthenol and curcumin.
- 3D-printed dressings were able to provide a supportive environment for cellular attachment, viability and growth.
- In vivo study showed that dressings exhibited marked improvements at all stages of the wound healing process.
Additionally, these 3D-printed materials showed a marked resistance to adherence of Staphylococcus aureus when compared to the PCL control 3D-printed samples, resulting in substantial reductions of up to 89.9% and 98.9% after incubation periods of 4 h and 24 h respectively. Although, all of the 3D-printed materials were able to provide a supportive environment for cellular attachment, viability and growth, the combination of both bioactive compounds CUR and DPA exhibited the most significant values for cell viability and proliferation.
In vivo wound healing study performed in Wistar rats showed that dressings containing these novel two compounds CUR and DPA exhibited marked improvement at any stage of the treatment process. Finally, histological examination revealed that dressings loaded with CUR and DPA also showed the best outcomes for all the evaluated parameters: (i) epithelisation, (ii) inflammatory reaction, (iii) proliferation rate of fibroblast and (iv) neoangiogenesis.
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Materials
Two different forms of PCL, CAPA™ 6506 (MW = 50,000 Da, i.e., high molecular weight), henceforth referred to as H-PCL, and CAPA™ 2054 (MW = 550 Da, i.e., low molecular weight), henceforth referred to as L-PCL, were both provided by Perstorp (Malmö, Sweden). LIG sample (BioPiva 190) was a softwood kraft LIG acquired by UPM (Helsinki, Finland). Both CUR (95%) and DPA (≥98%) were purchased from Alfa Aesar by Thermo Fisher Scientific (Lancashire, UK). Tween 80 (reagent grade) and phosphate-buffered saline (PBS) tablets to prepare PBS solution (pH 7.0) were both obtained from VWR (Lutterworth, UK). DPPH (2,2-diphenyl-1-picrylhydrazyl) was provided by Sigma Aldrich (Dorset, UK). Additionally, l-ascorbic acid E300 (ultrafine) was provided by DSM (Heerlen, the Netherlands). All materials and reagents were used as received. Tryptone soya broth (TSB), quarter-strength Ringer’s solution (QSRS) and Mueller-Hinton (MH) broth were obtained from Oxoid Ltd. (Hampshire, UK). Staphylococcus aureus NCTC 10788 was maintained in glycerol at −80 °C and cultivated in MH broth at 37 °C and at 100 rpm when required for the microbiological assessments.
Juan Domínguez-Robles, Elias Cuartas-Gómez, Sean Dynes, Emilia Utomo, Qonita Kurnia Anjani, Usanee Detamornrat, Ryan F. Donnelly, Natalia Moreno-Castellanos, Eneko Larrañeta, Poly(caprolactone)/lignin-based 3D-printed dressings loaded with a novel combination of bioactive agents for wound-healing applications, Sustainable Materials and Technologies, 2023, e00581, ISSN 2214-9937, https://doi.org/10.1016/j.susmat.2023.e00581.