Nanostructured Coatings Based on Graphene Oxide for the Management of Periprosthetic Infections.

To modulate the bioactivity and boost the therapeutic outcome of implantable metallic devices, biodegradable coatings based on polylactide (PLA) and graphene oxide nanosheets (nGOs) loaded with Zinforo™ (Zin) have been proposed in this study as innovative alternatives for the local management of biofilm-associated periprosthetic infections. Using a modified Hummers protocol, high-purity and ultra-thin nGOs have been obtained, as evidenced by X-ray diffraction (XRD) and transmission electron microscopy (TEM) investigations. The matrix-assisted pulsed laser evaporation (MAPLE) technique has been successfully employed to obtain the PLA-nGO-Zin coatings. The stoichiometric and uniform transfer was revealed by infrared microscopy (IRM) and scanning electron microscopy (SEM) studies. In vitro evaluation, performed on fresh blood samples, has shown the excellent hemocompatibility of PLA-nGO-Zin-coated samples (with a hemolytic index of 1.15%), together with their anti-inflammatory ability. Moreover, the PLA-nGO-Zin coatings significantly inhibited the development of mature bacterial biofilms, inducing important anti-biofilm efficiency in the as-coated samples. The herein-reported results evidence the promising potential of PLA-nGO-Zin coatings to be used for the biocompatible and antimicrobial surface modification of metallic implants.

Vimentin Cytoskeleton Architecture Analysis on Polylactide and Polyhydroxyoctanoate Substrates for Cell Culturing.

Polylactide (PLA), widely used in bioengineering and medicine, gained popularity due to its biocompatibility and biodegradability. Natural origin and eco-friendly background encourage the search of novel materials with such features, such as polyhydroxyoctanoate (P(3HO)), a polyester of bacterial origin. Physicochemical features of both P(3HO) and PLA have an impact on cellular response 32, i.e., adhesion, migration, and cell morphology, based on the signaling and changes in the architecture of the three cytoskeletal networks: microfilaments (F-actin), microtubules, and intermediate filaments (IF). To investigate the role of IF in the cellular response to the substrate, we focused on vimentin intermediate filaments (VIFs), present in mouse embryonic fibroblast cells (MEF). VIFs maintain cell integrity and protect it from external mechanical stress, and also take part in the transmission of signals from the exterior of the cell to its inner organelles, which is under constant investigation. Physiochemical properties of a substrate have an impact on cells' morphology, and thus on cytoskeleton network signaling and assembly. In this work, we show how PLA and P(3HO) crystallinity and hydrophilicity influence VIFs, and we identify that two different types of vimentin cytoskeleton architecture: network "classic" and "nutshell-like" are expressed by MEFs in different numbers of cells depending on substrate features.

The Application of (+)-Catechin and Polydatin as Functional Additives for Biodegradable Polyesters.

Plant polyphenols are a huge group of compounds with a wide spectrum of applications. Substances from this group have been used in polymer materials such as stabilizers, dyes, indicators, fungicides, and bactericides, especially in new generation packaging materials. The aim of this study is to obtain environmentally friendly materials based on the biodegradable aliphatic polyesters, polylactide (PLA) and polyhydroxyalkanoate (PHA), with plant functional additives, (+)-catechin and polydatin. These natural polyphenols (polydatin and (+)-catechin) have not been used so far in polymer materials (especially in biodegradable polyesters) as stabilizers, dyes, and indicators of aging. The application of polydatin and (+)-catechin as multifunctional additives for biodegradable polymers is a scientific novelty. This paper presents the following analyses of polyester materials: SEM microscopy, wide angle x-ray diffraction, mechanical properties, thermal analysis, surface free energy analysis, and determination of change of color after controlled UV exposure, thermal oxidation and weathering. Both PLA and PHA polyesters were characterized by higher resistance to oxidation and greater resistance to degradation under the influence of UV radiation. In addition, (+)-catechin was used simultaneously as a dye and an indicator of the aging time of polymeric materials. In contrast, polydatin did not dye polymers, but was a very good indicator of their lifetime, changing color under the influence of various external factors. Both polyphenols can be successfully used as natural additives for pro-ecological polyesters.

Vimentin Association with Nuclear Grooves in Normal MEF 3T3 Cells.

Vimentin, an intermediate filament protein present in leukocytes, blood vessel endothelial cells, and multiple mesenchymal cells, such as mouse embryonic fibroblasts (MEF 3T3), is crucial for various cellular processes, as well as for maintaining the integrity and durability (stability) of the cell cytoskeleton. Vimentin intermediate filaments (VIFs) adhere tightly to the nucleus and spread to the lamellipodium and tail of the cell, serving as a connector between the nucleus, and the cell's edges, especially in terms of transferring mechanical signals throughout the cell. How these signals are transmitted exactly remains under investigation. In the presented work, we propose that vimentin is involved in that transition by influencing the shape of the nucleus through the formation of nuclear blebs and grooves, as demonstrated by microscopic observations of healthy MEF (3T3) cells. Grooved, or "coffee beans" nuclei, have, to date, been noticed in several healthy cells; however, these structures are especially frequent in cancer cells-they serve as a significant marker for recognition of multiple cancers. We observed 288 MEF3T3 cells cultured on polyhydroxyoctanoate (PHO), polylactide (PLA), and glass, and we identified grooves, coaligned with vimentin fibers in the nuclei of 47% of cells cultured on PHO, 50% of cells on glass, and 59% of cells growing on PLA. We also observed nuclear blebs and associated their occurrence with the type of substrate used for cell culture. We propose that the higher rate of blebs in the nuclei of cells, cultured on PLA, is related to the microenvironmental features of the substrate, pH in particular.

Development of Antimicrobial Packaging Film Made from Poly(Lactic Acid) Incorporating Titanium Dioxide and Silver Nanoparticles.

Polylactide (PLA)/nano-TiO2 and PLA/nano-TiO2/nano-Ag blends films were prepared by a solvent volatilization method. Compared to pure PLA film, the nano-blend films have low water vapor permeability (WVP) and a poor transparency. With the increase of the NPs in the PLA, the tensile strength (TS) and elastic modulus (EM) decreased, while the elongation at break (ε) increased. SEM analysis indicated a rougher cross-section of the nano-blend films. According to the FTIR analysis, no new chemical bonds were formed in the nano-blend films. By using DSC to examine the crystallization and melting behavior, the result shows that the NPs have no effect on the glass transition (Tg) and melting temperature (Tm), but they caused an increase on the cold crystallization (Tc) and crystallinity (Xc). TGA results show that the addition of nanoparticles significantly improved the thermal stability. The PLA nano-blend films show a good antimicrobial activity against. E. coli and Listeria monocytogenes. Most important, we carried out migration tests, and verified that the release of NPs from the nano-blend films was within the standard limits.

Development of a Three-Dimensional (3D) Printed Biodegradable Cage to Convert Morselized Corticocancellous Bone Chips into a Structured Cortical Bone Graft.

This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D) printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire) fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft.

Greenhouse gas emissions from the treatment of household plastic containers and packaging: replacement with biomass-based materials.

The purpose of this study was to quantify the life-cycle greenhouse gas (GHG) emissions reduction that could be achieved by replacement of fossil-derived materials with biodegradable, biomass-based materials for household plastic containers and packaging, considering a variety of their treatment options. The biomass-based materials were 100% polylactide or a combination of polybutylene succinate adipate and polylactide. A scenario analysis was conducted considering alternative recycling methods. Five scenarios were considered: two for existing fossil-derived materials (the current approach in Japan) and the three for biomass-based materials. Production and waste disposal of 1 m(3) of plastic containers and packaging from households was defined as the functional unit. The results showed that replacement of fossil-derived materials with biomass-based materials could reduce life-cycle GHG emissions by 14-20%. Source separation and recycling should be promoted. When the separate collection ratio reached 100%, replacement with biomass-based materials could potentially reduce GHG emissions by 31.9%. Food containers are a priority for replacement, because they alone could reduce GHG emissions by 10%. A recycling system for biomass-based plastics must be carefully designed, considering aspects such as the transition period from fossil-derived plastics to biomass-based plastics.

OH End-Capped Silicone as an Effective Nucleating Agent for Polylactide-A Robotizing Method for Evaluating the Mechanical Characteristics of PLA/Silicone Blends.

Current research on materials engineering focuses mainly on bio-based materials. One of the most frequently studied materials in this group is polylactide (PLA), which is a polymer derived from starch. PLA does not have a negative impact on the natural environment and additionally, it possesses properties comparable to those of industrial polymers. The aim of the work was to investigate the potential of organosilicon compounds as modifiers of the mechanical and rheological properties of PLA, as well as to develop a new method for conducting mechanical property tests through innovative high-throughput technologies. Precise dosing methods were utilized to create PLA/silicone polymer blends with varying mass contents, allowing for continuous characterization of the produced blends. To automate bending tests and achieve comprehensive characterization of the blends, a self-created workstation setup has been used. The tensile properties of selected blend compositions were tested, and their ability to withstand dynamic loads was studied. The blends were characterized through various methods, including rheological (MFI), X-ray (XRD), spectroscopic (FTIR), and thermal properties analysis (TG, DSC, HDT), and they were evaluated using microscopic methods (MO, SEM) to examine their structures.

Hyaluronic Acid-Alginate Homogeneous Structures with Polylactide Coating Applied in Controlled Antibiotic Release.

The use of a controlled-release drug carrier is an innovative solution for the treatment of local infections, in particular in dentistry, skin diseases, and in open wounds. The biocompatibility, biodegradability, the possibility of a large amount of drug adsorbed (especially those with hydrophilic properties), and the ability to create structures of any shape and size are the reasons for hydrogels to be frequently studied. The main disadvantage of hydrogel carriers is the rapid rate of drug release; hence, in this study, an attempt was made to additionally chemically cross-link 1-ethyl-3-(3-dimethyl aminopropyl)-1-carbodiimide hydrochloride (EDC) with the hyaluronic acid-alginate (HA-SAL) structure. The answer to significantly reduce the mass flux typical for hydrogel structure was to surround it with a polymer layer using a dry cover. By coating the carriers with polylactide, the release time was increased by around forty times. As the carriers were designed to reduce local bacterial infections, among others in dentistry, the released antibiotics were amoxycillin, metronidazole, and doxycycline.

In vitro biocompatibility of polylactide and polybutylene succinate blends for urethral tissue engineering.

Surgical treatment of urothelial defects with autologous genital or extragenital tissue grafts is susceptible to complications. Tissue engineering utilizing novel biomaterials and cells such as human urothelial cells (hUC) for epithelial regeneration and adipose stromal cells (hASC) for smooth muscle restoration might offer new treatment options for urothelial defects. Previously, polylactide (PLA) has been studied for urethral tissue engineering, however, as such, it is too stiff and rigid for the application. Blending it with ductile polybutylene succinate (PBSu) could provide suitable mechanical properties for the application. Our aim was to study the morphology, viability and proliferation of hUC and hASC when cultured on 100/0 PLA/PBSu, 75/25 PLA/PBSu blend, 50/50 PLA/PBSu blend, and 0/100 PLA/PBSu discs. The results showed that the hUCs were viable and proliferated on all the studied materials. The hUCs stained pancytokeratin at 7 and 14 days, suggesting maintenance of the urothelial phenotype. The hASCs retained their viability and morphology and proliferated on all the other discs, except on PLA. On the PLA, the hASCs formed large aggregates with each other rather than attached to the material. The early smooth muscle cell markers SM22α and α-SMA were stained in hASC at 7 and 14 day time points on all PBSu-containing materials, indicating that hASCs maintain their smooth muscle differentiation potential also on PBSu. As a conclusion, PBSu is a highly potential biomaterial for urothelial tissue engineering since it supports growth and phenotypic maintenance of hUC and smooth muscle differentiation of hASC.

Robotization of Three-Point Bending Mechanical Tests Using PLA/TPU Blends as an Example in the 0-100% Range.

This article presents the development of an automated three-point bending testing system using a robot to increase the efficiency and precision of measurements for PLA/TPU polymer blends as implementation high-throughput measurement methods. The system operates continuously and characterizes the flexural properties of PLA/TPU blends with varying TPU concentrations. This study aimed to determine the effect of TPU concentration on the strength and flexural stiffness, surface properties (WCA), thermal properties (TGA, DSC), and microscopic characterization of the studied blends.

Preparation, Characterization and Evaluation of Antibacterial Properties of Polylactide-Polyethylene Glycol-Chitosan Active Composite Films.

Chitin is a natural biopolymer obtained from the exoskeleton of crustaceans. Chitosan is a derivative of chitin, which has antimicrobial properties and potential applications in several industries. Moreover, the composites of chitosan with other biodegradable polymers, such as polylactide (PLA) as packaging film, have shown promising results. In this study, chitosan was obtained and characterized from shrimp shells. Then, polylactide-chitosan composite films were prepared by a solvent casting technique using various amounts of chitosan (0.5-2% w/w) and polyethylene glycol as plasticizer (10% w/w). Thermal, mechanical properties, Fourier-transform infrared, scanning electron microscopy, as well as antibacterial properties of composite films were determined. It was found that adding chitosan (CH) into PLA films has a significant effect on tensile strength and no effect on thermal properties. The results showed a reduction on average of 1 log of colony-forming units against Staphylococcus aureus, while there is no antibacterial effect against Salmonella typhimurium. The study proved the antibacterial effect of CH in films of PLA against Gram-positive bacteria and appropriate mechanical properties. These films could be used for the development of biodegradable/eco-friendly food packaging prototypes, as a potential solution to replace conventional non-degradable packaging materials.

Development and Characterization of Polylactide Blends with Improved Toughness by Reactive Extrusion with Lactic Acid Oligomers.

In this work, we report the development and characterization of polylactide (PLA) blends with improved toughness by the addition of 10 wt.% lactic acid oligomers (OLA) and assess the feasibility of reactive extrusion (REX) and injection moulding to obtain high impact resistant injection moulded parts. To improve PLA/OLA interactions, two approaches are carried out. On the one hand, reactive extrusion of PLA/OLA with different dicumyl peroxide (DCP) concentrations is evaluated and, on the other hand, the effect of maleinized linseed oil (MLO) is studied. The effect of DCP and MLO content used in the reactive extrusion process is evaluated in terms of mechanical, thermal, dynamic mechanical, wetting and colour properties, as well as the morphology of the obtained materials. The impact strength of neat PLA (39.3 kJ/m2) was slightly improved up to 42.4 kJ/m2 with 10 wt.% OLA. Nevertheless, reactive extrusion with 0.3 phr DCP (parts by weight of DCP per 100 parts by weight of PLA-OLA base blend 90:10) led to a noticeable higher impact strength of 51.7 kJ/m2, while the reactive extrusion with 6 phr MLO gave an even higher impact strength of 59.5 kJ/m2, thus giving evidence of the feasibility of these two approaches to overcome the intrinsic brittleness of PLA. Therefore, despite MLO being able to provide the highest impact strength, reactive extrusion with DCP led to high transparency, which could be an interesting feature in food packaging, for example. In any case, these two approaches represent environmentally friendly strategies to improve PLA toughness.

Tungsten disulfide nanotubes enhance flow-induced crystallization and radio-opacity of polylactide without adversely affecting in vitro toxicity.

Treatment of vascular disease, from peripheral ischemia to coronary heart disease (CHD), is poised for transformation with the introduction of transient implants designed to "scaffold" regeneration of blood vessels and ultimately leave nothing behind. Improved materials could expand the use of these devices. Here, we examine one of the leading polymers for bioresorbable scaffolds (BRS), polylactide (PLA), as the matrix of nanocomposites with tungsten disulfide (WS2) nanotubes (WSNT), which may provide mechanical reinforcement and enhance radio-opacity. We evaluate in vitro cytotoxicity using vascular cells, flow-induced crystallization and radio-opacity of PLA-WSNT nanocomposites at low WSNT concentration. A small amount of WSNT (0.1 wt%) can effectively promote oriented crystallization of PLA without compromising molecular weight. And radio-opacity improves significantly: as little as 0.5 to 1 wt% WSNT doubles the radio-opacity of PLA-WSNT relative to PLA at 17 keV. The results suggest that a single component, WSNT, has the potential to increase the strength of BRS to enable thinner devices and increase radio-opacity to improve intraoperative visualization. The in vitro toxicity results indicate that PLA-WSNT nanocomposites are worthy of investigation in vivo. Although substantial further preclinical studies are needed, PLA-WSNT nanocomposites may provide a complement of material properties that may improve BRS and expand the range of lesions that can be treated using transient implants. STATEMENT OF SIGNIFICANCE: Bioresorbable Scaffolds (BRSs) support regeneration of arteries without permanent mechanical constraint. Poly-L-lactide (PLLA) is the structural material of the first approved BRS for coronary heart disease (ABSORB BVS), withdrawn due to adverse events in years 1-3. Here, we examine tungsten disulfide (WS2) nanotubes (WSNT) in PLA to address two contributors to early complications: (1) reinforce PLLA (enable thinner BRS), and (2) increase radiopacity (provide intraoperative visibility). For BRS, it is significant that WSNT disperse, remain dispersed, reduce friction and improve mechanical properties without additional chemicals or surface modifications. Like WS2 nanospheres, bare WSNT and PLA-WSNT nanocomposites show low cytotoxicity in vitro. PLA-WSNT show enhanced flow-induced crystallization relative to PLA, motivating future study of the processing behavior and strength of these materials.

Study on the anti-infection ability of vancomycin cationic liposome combined with polylactide fracture internal fixator.

A polylactide composite fracture fixator loaded with vancomycin cationic liposome (PLA@VL) was prepared by reverse evaporation method. The method of cationic liposome encapsulating vancomycin could effectively improve antibacterial property and achieve drug sustained release effect, so as to reduce toxicity of antibiotics in vivo. Scanning electron microscope (SEM) was used to observe morphology and Fourier transform infrared spectroscopy (FTIR) was used to detect the composition of the internal fixator. In vitro drug release model, in vitro degradation model and body fluid osteogenesis model were designed in this study. On the other hand, the experiments of inhibition zone and MC3T3-E1 osteoblasts in mice were conducted to explore antibacterial property, cell activity and adhesion of the PLA@VL composite internal fixator. Alkaline phosphatase (ALP) staining method and alizarin red assay were used to detect the osteogenic induction ability of the composite internal fixator. Finally, mice fracture models were established to verify osteogenic and anti-infection abilities of the composite internal fixator in vivo. The results showed that MC3T3-E1 cells had better adhesion and proliferation abilities on the PLA@VL composite internal fixator than on the PLA fixator, which indicated that the PLA@VL composite internal fixator possessed excellent osteogenic and anti-infection abilities both in vivo and in vitro. Therefore, the above experiments showed that the fracture internal fixator combined with vancomycin cationic liposome had better biocompatibility, antibacterial ability and osteogenic ability, which provides a promising anti-infection material for the clinical field of fracture.

Insight into melting point depression of polylactide nanocomposites with acetylated chitin nanocrystals.

Chitin nanocrystal (ChNC) was used to prepare fully biodegradable nanocomposites with polylactide (PLA). The nucleation and melting behavior of nanocomposites were studied with the objective to correlate PLA-ChNC affinity to PLA crystallization. The results disclose that the PLA nanocomposites with pristine ChNCs and the ones with acetylated ChNCs show completely different nucleation and melting behavior because the role of ChNCs is altered after acetylation. Pristine ChNC acts as inert filler, with weak nucleating activity, while acetylated ChNCs as anti-nucleation agent, restraining crystallization of PLA. Accordingly, the nanocomposites with acetylated ChNCs show melting point depression, with reduced nucleation capability. The recrystallization and self-nucleation, as well as the double-melting behaviors were then studied in terms of acetylation levels of ChNCs and annealing temperatures, in order to better understand the relations between two-phase affinity and PLA chain dynamics. This work provides interesting information around designing thermal properties of the ChNC-filled PLA nanocomposites.

Biodegradable Polyester Materials Containing Gallates.

Gallates are widely used as antioxidants in the food and cosmetics industries. The purpose of the study was to obtain pro-ecological materials based on biodegradable polyesters, such as polylactide (PLA) and polyhydroxyalkanoate (PHA), and gallates. Gallates (ethyl, propyl, octyl, and lauryl) have not been used so far in biodegradable polymers as stabilizers and indicators of aging. This manuscript examines the properties of gallates such as antioxidant capacity and thermal stability. This paper also presents the following analyses of polymer materials: specific migration of gallates from polymers, SEM microscopy, differential scanning calorimetry (DSC), wide-angle X-ray diffraction, mechanical properties, surface free energy, and determination of change of color after controlled UV exposure, thermooxidation, and weathering. All gallates showed strong antioxidant properties and good thermal stability. Due to these properties, in particular their high oxidation temperature, gallates can be successfully used as polyester stabilizers. Biodegradable polyesters containing gallates can be an environmentally friendly alternative to petrochemical packaging materials.

Enhanced Mechanical Stability and Biodegradability of Ti-Infiltrated Polylactide.

Biodegradable polymers have been often used in place of conventional nondegradable polymers for industrial and medical applications. In particular, polylactide (PLA) has been regarded as a popular ecofriendly plastic and has many advantages like good biocompatibility and processability. Yet, it still has some drawbacks in mechanical properties. Here, we prepared Ti-infiltrated PLA by mimicking the gelatinous jaw of a seaworm whose mechanical properties are toggled up and down by the tiny amount of metal ions, expecting to prepare a new type of alternative. Ti induced significant chemical and microstructural changes in the PLA, which led to a notable improvement in the mechanical properties as compared to the neat PLA. The Ti-infiltrated PLA exhibited high resistance to rapid degradation. More importantly, the toxicity assessment demonstrated that the resulting PLA is still biocompatible and nontoxic. Consequently, we proved that the Ti-infiltrated PLA has high mechanical properties comparable to conventional nondegradable polymers and good biocompatibility as well as delayed biodegradability. We anticipate the current Ti-infiltrated PLA to be an ecofriendly replacement of some conventional plastics, which helps preserve a green environment.

Mechanical and Thermal Properties of Polylactide (PLA) Composites Modified with Mg, Fe, and Polyethylene (PE) Additives.

In this article, polylactic acid-based composites reinforced with 5% of polyethylene, iron, and magnesium powders were prepared by extrusion and compressed under the pressure of about 10 MPa and characterized. These composites were mechanically, thermally, and morphologically evaluated. It was found, compared to the pure polylactic acid (PLA), an improvement in tensile strength (both σ and YS0.2) was obtained for the composite with the iron powder addition, while the magnesium powder slightly improved the ductility of the composite material (from 2.0 to 2.5%). Degradation studies of these composites in the 0.9% saline solution over a period of 180 days revealed changes in the pH of the solution from acidic to alkaline, in all samples. The most varied mass loss was observed in the case of the PLA-5%Mg sample, where initially the sample mass increased (first 30 days) then decreased, and after 120 days, the mass increased again. In the context of degradation phenomenon of the tested materials, it turns out that the most stable is the PLA composite with the Fe addition (PLA-5%Fe), with highest tensile strength and hardness.

Tumor Responsive and Tunable Polymeric Platform for Optimized Delivery of Paclitaxel to Treat Glioblastoma.

Current interstitial therapies for glioblastoma can overcome the blood-brain barrier but fail to optimally release therapy at a rate that stalls cancer reoccurrence. To address this lapse, acetalated dextran (Ace-DEX) nanofibrous scaffolds were used for their unique degradation rates that translate to a broad range of drug release kinetics. A distinctive range of drug release rates was illustrated via electrospun Ace-DEX or poly(lactic acid) (PLA) scaffolds. Scaffolds composed of fast, medium, and slow degrading Ace-DEX resulted in 14.1%, 2.9%, and 1.3% paclitaxel released per day. To better understand the impact of paclitaxel release rate on interstitial therapy, two clinically relevant orthotopic glioblastoma mouse models were explored: (1) a surgical model of resection and recurrence (resection model) and (2) a distant metastasis model. The effect of unique drug release was illustrated in the resection model when a 78% long-term survival was observed with combined fast and slow release scaffolds, in comparison to a survival of 20% when the same dose is delivered at a medium release rate. In contrast, only the fast release rate scaffold displayed treatment efficacy in the distant metastasis model. Additionally, the acid-sensitive Ace-DEX scaffolds were shown to respond to the lower pH conditions associated with GBM tumors, releasing more paclitaxel in vivo when a tumor was present in contrast to nonacid sensitive PLA scaffolds. The unique range of tunable degradation and stimuli-responsive nature makes Ace-DEX a promising drug delivery platform to improve interstitial therapy for glioblastoma.