Abstract
A surgical suture is a medical device that holds body tissues together after surgery, injury, or other medical procedures, which often pose the risk of surgical site infections (SSIs). Drug-eluting sutures with antimicrobial or anti-inflammatory properties have been developed to combat this. However, including active pharmaceutical ingredients (APIs) typically compromises the tensile strength of the sutures.
This thesis introduces a groundbreaking approach: a drug-eluting suture constructed with drug-loaded microspheres uniformly distributed throughout the suture body. This innovative model maintains the necessary mechanical properties and offers antioxidant, antibacterial, and anti-inflammatory benefits for wound healing.
Curcumin, a natural bioactive compound found in turmeric, was chosen as the model drug because it has the aforementioned properties to build the surgical suture drug delivery system. Biodegradable polymers such as polycaprolactone (PCL), polylactic acid (PLA), and polyethylene glycol (PEG) are FDA-approved and commonly used in skin tissue regeneration and wound healing. Curcumin-loaded PLA (Cur-PLA) microspheres were prepared using the oil-in-water single emulsion solvent evaporation method. Dichloromethane (DCM) was used as the oil phase, and polyvinyl alcohol (PVA) was used as the aqueous phase. The results indicated that using a 3% w/v PVA solution, maintaining an oil-to-water phase ratio of 1:7 v/v, and stirring at 1000 rpm for 6 h resulted in the production of microspheres with an average particle size of 34.32 ± 12.82 μm. Increasing the PVA concentration in the aqueous phase led to the formation of smaller Cur-PLA particle sizes. However, increasing the PVA concentration beyond 3% w/v caused particle aggregation after lyophilisation. Additionally, incorporating curcumin into the microsphere composition decreased the melting temperature of PLA due to the interaction with curcumin, causing PLA to transition from a crystalline to an amorphous state.
The sutures were fabricated by mixing Cur-PLA microspheres with PCL and PEG using a melt-extrusion procedure, followed by a drawing process to achieve the desired suture diameters and improve their mechanical strength. The sutures, containing 3%, 5%, and 7% w/w microspheres, had diameters ranging from 0.34 to 0.40 mm after being drawn and showed prolonged drug release for up to 14 days. Among these, the 3% w/w microsphere loading sutures exhibited excellent mechanical strength of 165.02±18.61 MPa. Furthermore, the thermally drawn suture demonstrated increased crystallinity compared to the non-stretched suture due to the improved alignment of chain molecules that induced crystallisation.
In the next phase of the study, PCL and PEG were included in the production of curcumin-loaded microspheres to adjust drug release profiles and enhance the mechanical strength of the sutures. These microspheres exhibited improved drug loading capacity, encapsulation efficiency, and reduced particle sizes compared to the previous Cur-PLA microspheres. Additionally, the hydrophilic properties of PEG altered the microspheres' morphology from smooth, round surfaces to coarse surfaces. Adding PEG also reduced the melting temperature and crystallinity of PLA-based microspheres, resulting in a faster curcumin release. The suture containing Cur-PLA-PEG-PCL microspheres had the highest tensile strength of 170.20±22.73 MPa due to the incorporation of PCL into the microspheres. Meanwhile, the suture containing Cur-PLA-PEG microspheres had a relatively stable breaking strength during degradation, remaining at 89.96% of its original strength on day 14. All sutures showed a homogeneous distribution of microspheres under the fluorescence microscope.
Finally, all sutures demonstrated non-toxicity towards a human keratinocyte cell line (HaCaT) and normal human dermal fibroblasts (NHDFs) in the in vitro biocompatibility studies. Furthermore, all suture samples exhibited antibacterial and anti-inflammatory activities, and there was a direct relationship between the duration of incubation of sutures and their antioxidant potential.
Overall, the findings of this thesis showed that these innovative microsphere-loaded sutures hold significant potential as a medical device for wound healing.