Speaker
Description
"Introduction
Bioresorbable stents (BRS) are designed to provide a temporary support to the vessel wall while the structure slowly degrades until completely resorbed. In order to prevent neointimal hyperplasia, antiproliferative drugs such as everolimus are loaded into stents, although endothelialization may be delayed due to long release periods [1]. Additive manufacturing (AM) and electrospinning (ES) are separate approaches to manufacturing scaffolds for a variety of tissue engineering applications. Previously, we have developed a versatile AM fabrication strategy for stents by using polymeric inks and direct-writing onto a rotating cylinder that allows patient-specific customization [2].
The aim of this work is to combine AM and ES to generate new biomimetic drug-eluting BRS for cardiovascular applications.
Methodology
Poly-L-lactic acid (PLLA) and poly(lactic-co-caprolactone) (PLCL) stents were obtained by cylindrical printing onto a rotating mandrel with 3 mm in diameter [2]. The ink consisted in a solution of PLLA (PL 65, Purac) or PLCL copolymer (PLC 9538, Purac) in chloroform at 10% w/v and 12.5% w/v, respectively. Inks were further modified with the addition of antiproliferative drug everolimus at 2 wt.% and 4 wt.% with respect to polymer content. An alternative drug-loading method was developed by means of ES by dissolution of PLCL pellets in chloroform and ethanol (7:3 ratio) at 6.25% w/v with everolimus at 35 wt.% with respect to polymer content. 3D-printed stents were mounted onto a grounded collector mandrel showing both rotation and longitudinal movement. Obtained drug-loaded scaffolds were incubated in 5 mL of release medium (0.7% Triton X-405 in 0.01 M potassium phosphate buffer pH 6 at 37ºC in 7% acetonitrile) to evaluate everolimus release by HPLC [3]. Finally, in vitro cell migration studies with HUVECs and SMCs were performed.
Results
Biomimetic drug-eluting BRS were successfully fabricated either by AM or by combination of AM and ES techniques. On the one hand, PLLA and PLCL stents showed drug entrapment within stents' struts. Everolimus release assays showed initial fast release due to surface-available drug followed by a sustained release over 4 weeks. Drug release was subjected to polymer degradation and found to be higher for PLCL stents than for PLLA stents. On the other hand, ES resulted in a homogeneous coating wrapping the entire stent. Although ES-coated BRS showed the same release trend, everolimus release rate was found to be higher than for AM drug-loaded stents. Moreover, fiber orientation and everolimus release of AM/ES BRS directed HUVECs and SMCs adhesion, proliferation and migration.
Conclusions
Two different PLLA and PLCL drug-eluting BRS were successfully fabricated by means of AM or AM/ES combined techniques. The AM/ES BRS resulted in a fiber-coated drug-loaded biomimetic BRS able to inhibit neointimal hyperplasia while controlling endothelialization.
Acknowledgements
Financial support was received from Spanish Government, MINECO/FEDER (RTI2018-098075-B-C21) and the Government of Catalonia (AGAUR 2017 SGR 1165, BASE3D 001-P-001646).
References
[1] McMahon, S. et al., Prog. Polym. Sci. 83, 79-96 (2018).
[2] Chausse, V. et al., Addit. Manuf. 102392 (2021).
[3] Kamberi, M. et al., Eur. J. Pharm. Sci. 37 (3-4), 217–222 (2009)."
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