Stereocomplex Polylactide for Drug Delivery and Biomedical Applications: A Review.

Polylactide (PLA) is among the most common biodegradable polymers, with applications in various fields, such as renewable and biomedical industries. PLA features poly(D-lactic acid) (PDLA) and poly(L-lactic acid) (PLLA) enantiomers, which form stereocomplex crystals through racemic blending. PLA emerged as a promising material owing to its sustainable, eco-friendly, and fully biodegradable properties. Nevertheless, PLA still has a low applicability for drug delivery as a carrier and scaffold. Stereocomplex PLA (sc-PLA) exhibits substantially improved mechanical and physical strength compared to the homopolymer, overcoming these limitations. Recently, numerous studies have reported the use of sc-PLA as a drug carrier through encapsulation of various drugs, proteins, and secondary molecules by various processes including micelle formation, self-assembly, emulsion, and inkjet printing. However, concerns such as low loading capacity, weak stability of hydrophilic contents, and non-sustainable release behavior remain. This review focuses on various strategies to overcome the current challenges of sc-PLA in drug delivery systems and biomedical applications in three critical fields, namely anti-cancer therapy, tissue engineering, and anti-microbial activity. Furthermore, the excellent potential of sc-PLA as a next-generation polymeric material is discussed.

Current status and future direction of biodegradable metallic and polymeric vascular scaffolds for next-generation stents.

Because of the increasing incidence of coronary artery disease, the importance of cardiovascular stents has continuously increased as a treatment of this disease. Biodegradable scaffolds fabricated from polymers and metals have emerged as promising materials for vascular stents because of their biodegradability. Although such stent framework materials have shown good clinical efficacy, it is difficult to decide whether polymers or metals are better vascular scaffolds because their properties are different. Therefore, there are still obstacles in the development of biodegradable vascular scaffolds in terms of improving clinical efficacy. This review analyzes the pros and cons of current stent materials with respect to five key factors for next-generation stent and discusses methods of improvement. Furthermore, we discuss biodegradable electronic stents with electrical conductivity, which has been considered unimportant until now, and highlight electrical conductivity as a key factor in the development of next-generation stents.

Biodegradable vascular stents with high tensile and compressive strength: a novel strategy for applying monofilaments via solid-state drawing and shaped-annealing processes.

Monofilaments such as those consisting of polyamide (PA), polydioxanone (PDS), and poly(vinylidene fluoride) (PVDF), have been commonly used in various industries. However, most are non-biodegradable, which is unfavorable for many biomedical applications. Although biodegradable polymers offer significant benefits, they are still limited by their weak mechanical properties, which is an obstacle for use as a biomaterial that requires high strength. To overcome the current limitations of biodegradable monofilaments, a novel solid-state drawing (SSD) process was designed to significantly improve the mechanical properties of both PA and poly(l-lactic acid) (PLLA) monofilaments in this study. Both PA and PLLA monofilaments exhibited more than two-fold increased tensile strength and a highly reduced thickness using SSD. In X-ray diffraction and scanning electron microscopy analyses, it was determined that SSD could not only promote the α-crystal phase, but also smoothen the surface of PLLA monofilaments. To apply SSD-monofilaments with superior properties to cardiovascular stents, a shaped-annealing (SA) process was designed as the follow-up process after SSD. Using this process, three types of vascular stents could be fabricated, composed of SSD-monofilaments: double-helix, single-spring and double-spring shaped stents. The annealing temperature was optimized at 80 °C to minimize the loss of mechanical and physical properties of SSD-monofilaments for secondary processing. All three types of vascular stents were tested according to ISO 25539-2. Consequently, it was confirmed that spring-shaped stents had good recovery rate values and a high compressive modulus. In conclusion, this study showed significantly improved mechanical properties of both tensile and compressive strength simultaneously and extended the potential for biomedical applications of monofilaments.

Poly(L-lactic acid) scaffold with oriented micro-valley surface and superior properties fabricated by solid-state drawing for blood-contact biomaterials.

Most biomaterials composed of biodegradable polymers will contact either accidentally or consistently with blood and this commonly requires both good  mechanical strength and blood compatibility. Despite this demand, current processing methods still make it difficult and complex to simultaneously improve the two properties. To overcome present limitations, the aim of this work is to develop a solid-state drawing which is a novel method for blood-contact biomaterials that can simultaneously improve the two essential factors of mechanical strength and blood compatibility, as well as induce a micro-patterned surface. Solid-state drawn (SSD) poly(L-lactic acid) (PLLA) film significantly maximally increased tensile strength and elastic modulus about ninefold and sixfold, respectively, compared to undrawn film. Furthermore, it was determined that SSD-PLLA film had highly developed molecular orientation, higher crystallinity and surface hydrophobicity. Additionally, the SSD method could greatly reduce roughness of the surface and induce the formation of aligned valleys, forming microstructures on the film surface. The topographical cue delayed hydrolytic degradation and prevented damage on the surface by NaOH of alkali compounds are compared with undrawn film. In energy-dispersive x-ray spectroscopy analysis, the surface of SSD film treated by NaOH was not detected on any ions whereas undrawn film held foreign ions on surface defects. The hemolysis rate of SSD film was considerably decreased with an increase of draw ratio up to 0.2% maximally and SSD film has shown greatly lower platelet adhesion compared to undrawn film in blood-compatibility analysis. Interestingly, one-directional alignment of micro-valley structure on SSD film could promote initial adhesion of human umbilical vein endothelial cells (HUVEC) compared with undrawn film and guide the direction of HUVEC. In conclusion, the newly designed SSD method has shown potential for developing blood-contact biomaterials simply due to great mechanical properties, blood compatibility and an aligned micro-patterned surface.