Purpose: 3D printed polycaprolactone (PCL)-blended scaffolds have been designed, prepared and evaluated in this study prior to the incorporation of a polyvinyl alcohol-polyacrylic acid (PVA-PAA) hydrogel for the delivery of in situ-formed sodium indomethacin. The prepared PCL-PVA-PAA scaffold is proposed as a structural support system for load-bearing tissue damage where inflammation is prevalent.
Methods: The polycaprolactone scaffold was designed using Magics ® V18 design software and 3-D printed using an Envisontec® 3-D Bioplotter (Envisontec® GmbH, Gladbeck, Germany) prior to the incorporation of a 6% PVA-PAA hydrogel. Analyses undertaken included uniaxial testing using a CellScale BioTester 5000 (CellScale, Canada) in addition to its thermal, structural and porosimetric properties. The viscoelastic properties of the incorporated PVA-PAA hydrogel has also been determined using an Elasto-SensTM Bio (Rheolution, Montreal, Canada) viscoelasticity analyser. Additionally, the drug release properties and uniaxial strength of the PCL-PVA-PAA scaffold was evaluated.
Results: DSC analysis of the PCL blend revealed A single melting endotherm depicting a melting point temperature of 57.81 °C. TMDSC profile of the PCL blend revealed that the endothermic transition occurred at approx. 32 minutes or 51 °C, marginally lower than the DSC profile.
Porosity studies undertaken indicated a reversible Type III isotherm for the PCL blend, with an uptake of 1.25 cm3/g due to the hindrance of the multilayer nature of the polymer. The pore volume of was determined to be 43.001 Å with an uptake of 2.7 cm3/g.
Viscoelastic evaluation of the PVA-PAA hydrogel determined that at the beginning of the analysis, G’ was larger (19510 Pa) than G” (390.2 Pa) and therefore the hydrogel behaves as a semi-solid. At 400 min, G” was greater than G’, indicating that a less solid-like behaviour. As the analysis proceeded, tan δ as well as the shear complex modulus (G*) approached 1.00. The tan δ did not exceed 1 for the reminder of the study validating that it remained as a hydrogel and not a liquid state. The hydrogel did not undergo significant fluctuations in height (9.2 - 15.0 mm) over the test period. Synthesis validation of the PCL scaffold determined bands at 2942 cm-1, indicative of asymmetric CH2 stretching and strong bands seen around 1725 cm-1 representative of carbonyl stretching. Additionally, at 1110 cm-1, C–O and C–C stretching in the amorphous phase of the blend was determined. The FTIR spectra of the PVA-PAA hydrogel revealed a peak at 2919 cm-1, indicative of C-H stretching pertaining to PVA, a peak at 1537.06 cm−1 attributed to NH2 deformation and peaks around 1636.4 cm−1 assigned to the amide I bands due to cross-linking by N,N'-methylenebisacrylamide. Mechanical strain evaluation of the PCL scaffolds without the added PVA-PAA hydrogel detailed minimal differences between hydrated and anhydrous scaffold samples (Figure 2). Results of this analysis detailed that the hydrous PCL scaffold had a greater resistance to strain with a maximum displacement of 893 µm and a Modulus of 174.51 KPa compared with the anhydrous scaffold which had a maximum displacement of 1047 µm and a Modulus of 166.21 KPa. A similar result was determined for PCL-PVA-PAA scaffolds where the hydrated PPP scaffold (Figure 2) noted a maximum displacement of 464 µm and a Modulus of 219.84 and the anhydrous PAA scaffold was determined to have a maximum displacement of 633 µm and a Modulus of 202.04 KPa. Analysis of the release of sodium indomethacin from the PCL-PVA-PAA scaffold (Figure 3) detailed an initial burst release of weakly-bound highly hydrophilic sodium indomethacin (41%) from the PCL-PVA-PAA scaffold within the first 30 minutes with 65 % released in the first hour. Evaluation from Hour 2 (60 minutes) to Hour 8 (480 minutes) determined 83 % drug release after 8 hours. These results were in correlation with the increase in hydrogel height due to swelling.
Conclusion: This study provides for an interesting application of a 3-D printed polymeric drug delivery platform which additionally provides structural support for damaged load-bearing tissue. Analysis of the 3-D printed scaffolds highlighted its ability to be used as a reinforcement platform for load-bearing tissue support whilst also providing delivery of sodium indomethacin for the treatment of inflammation.
Sunaina Indermun– Post-Doctoral Research Fellow, University of the Witwatersrand, Johannesburg, Gauteng
Pradeep Kumar– Senior Researcher: Wits Advanced Drug Delivery Platform, University of the Witwatersrand, JHB, Gauteng
Yahya Choonara– Chairman and Head I Pharmacy and Pharmacology, University of the Witwatersrand, JHB, Gauteng
Viness Pillay– Director: Wits Advanced Drug Delivery Platform, University of the Witwatersrand, JHB, Gauteng