Chitosan grafted/cross-linked with biodegradable polymers: A review.

Public perception of polymers has been drastically changed with the improved plastic management at the end of their life. However, it is widely recognised the need of developing biodegradable polymers, as an alternative to traditional petrochemical polymers. Chitosan (CH), a biodegradable biopolymer with excellent physiological and structural properties, together with its immunostimulatory and antibacterial activity, is a good candidate to replace other polymers, mainly in biomedical applications. However, CH has also several drawbacks, which can be solved by chemical modifications to improve some of its characteristics such as solubility, biological activity, and mechanical properties. Many chemical modifications have been studied in the last decade to improve the properties of CH. This review focussed on a critical analysis of the state of the art of chemical modifications by cross-linking and graft polymerization, between CH or CH derivatives and other biodegradable polymers (polysaccharides or proteins, obtained from microorganisms, synthetized from biomonomers, or from petrochemical products). Both techniques offer the option of including a wide variety of functional groups into the CH chain. Thus, enhanced and new properties can be obtained in accordance with the requirements for different applications, such as the release of drugs, the improvement of antimicrobial properties of fabrics, the removal of dyes, or as scaffolds to develop bone tissues.

Waterborne Polyurethane Dispersions and Thin Films: Biodegradation and Antimicrobial Behaviors.

Biodegradable and antimicrobial waterborne polyurethane dispersions (PUDs) and their casted solid films have recently emerged as important alternatives to their solvent-based and non-biodegradable counterparts for various applications due to their versatility, health, and environmental friendliness. The nanoscale morphology of the PUDs, dispersion stability, and the thermomechanical properties of the solid films obtained from the solvent cast process are strongly dependent on several important parameters, such as the preparation method, polyols, diisocyanates, solid content, chain extension, and temperature. The biodegradability, biocompatibility, antimicrobial properties and biomedical applications can be tailored based on the nature of the polyols, polarity, as well as structure and concentration of the internal surfactants (anionic or cationic). This review article provides an important quantitative experimental basis and structure evolution for the development and synthesis of biodegradable waterborne PUDs and their solid films, with prescribed macromolecular properties and new functions, with the aim of understanding the relationships between polymer structure, properties, and performance. The review article will also summarize the important variables that control the thermomechanical properties and biodegradation kinetics, as well as antimicrobial and biocompatibility behaviors of aqueous PUDs and their films, for certain industrial and biomedical applications.

Fate of Biodegradable Engineered Nanoparticles Used in Veterinary Medicine as Delivery Systems from a One Health Perspective.

The field of veterinary medicine needs new solutions to address the current challenges of antibiotic resistance and the need for increased animal production. In response, a multitude of delivery systems have been developed in the last 20 years in the form of engineered nanoparticles (ENPs), a subclass of which are polymeric, biodegradable ENPs, that are biocompatible and biodegradable (pbENPs). These platforms have been developed to deliver cargo, such as antibiotics, vaccines, and hormones, and in general, have been shown to be beneficial in many regards, particularly when comparing the efficacy of the delivered drugs to that of the conventional drug applications. However, the fate of pbENPs developed for veterinary applications is poorly understood. pbENPs undergo biotransformation as they are transferred from one ecosystem to another, and these transformations greatly affect their impact on health and the environment. This review addresses nanoparticle fate and impact on animals, the environment, and humans from a One Health perspective.

Coronary bifurcations treated with thin-strut drug-eluting stents: a prespecified analysis of the randomized BIO-RESORT trial.

BACKGROUND: Treatment of a coronary bifurcation lesion is often required in routine clinical practice, but data on the performance of very thin-strut biodegradable polymer drug-eluting stents are scarce. METHODS: Comparison of biodegradable polymer and durable polymer drug-eluting stents in an all comers population (BIO-RESORT) is a prospective, multicenter randomized clinical trial that included 3514 all-comer patients, who were randomized to very thin-strut biodegradable polymer-coated sirolimus- or everolimus-eluting stents, versus thin-strut durable polymer-coated zotarolimus-eluting stents. The approach of bifurcation stenting was left at the operator's discretion, and provisional stenting was generally preferred. This prespecified analysis assessed 3-year clinical outcome of all patients in whom treatment involved at least one bifurcation with a side-branch diameter ≥1.5 mm. RESULTS: Of all BIO-RESORT trial participants, 1236 patients were treated in bifurcation lesions and analyzed. Single- and two-stent techniques were used in 85.8% and 14.2%, respectively. 'True' bifurcation lesions (main vessel and side-branch obstructed) were treated in 31.1%. Three-year follow-up was available in 1200/1236 (97.1%) patients. The main endpoint target vessel failure (composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization) occurred in sirolimus-eluting stents in 42/412 (10.3%) and in zotarolimus-eluting stents in 49/409 (12.1%) patients (P-logrank = 0.40). In everolimus-eluting stents, target vessel failure occurred in 40/415 (9.8%) patients (vs. zotarolimus-eluting stents: P-logrank = 0.26). There was no between-stent difference in individual components of target vessel failure. Findings were consistent in patients with single-vessel treatment and patients treated with a single-stent technique. CONCLUSIONS: Three years after stenting all-comers with bifurcation lesions, clinical outcome was similar with the sirolimus-eluting and everolimus-eluting stents versus the zotarolimus-eluting stent.

A bio-degradable synthetic membrane to treat superficial and deep second degree burn wounds in adults and children - 4 year experience.

INTRODUCTION: A new bio-degradable synthetic membrane was recently introduced to treat second degree burns in adults and pediatric patients. OBJECTIVE: To assess complications and outcomes using this absorbable synthetic membrane to treat second degree burns. METHODS: 229 burn patients, 138 pediatric, with superficial and deep second -degree wounds, treated with the absorbable synthetic membrane (Suprathel®, Polymedics, Denkendorf, Germany) were included in this study. Patients were treated under anesthesia or moderate sedation. The wound bed was prepared by using either rough debridement or dermabrasion excision. After hemostasis, the membrane was applied to the wound with an outer layer dressing of fatty gauze, bridal veil, absorptive gauze and an ACE® wrap. The outer dressing was removed every one to four days, depending on exudate, in order to closely follow the wound through the translucent membrane and fatty gauze layers. After complete epithelialization, the dressing separated and could be removed. The study focused on the need for subsequent grafting, healing time, patient pain level, hypertrophic scarring and rate of infection. RESULTS: All wounds in this study that were treated with Suprathel® healed without grafting. The average TBSA (Total Body Surface Area) was 8.9% (1%-60%). Average time to healing was 13.7 days for ≥ 90% epithelialization with 11.9 days for pediatric patients versus 14.7 days for adults. Throughout the treatment period, the average pain level was 1.9 on a 10-point scale. 27 patients developed hypertrophic scarring in some areas (11.7%). Average Length of stay (LOS) was 6.9 days. The rate of infection was 3.8% (8/229). Failure or progression to full thickness in part of the wounds was 5.2% (12/229). CONCLUSION: In treating second degree burn wounds, this membrane provides a simple, effective solution alternative with good outcomes and less pain than conventional and previously studied treatment options in the same institution. Fewer dressing changes and easier overall management of the wounds contribute to its favorable profile.

Biodegradable Nanoparticles: A Recent Approach and Applications.

Biodegradable nanoparticles (NPs) are the novel carriers for the administration of drug molecules. Biodegradable nanoparticles have become popular recently because of their special features such as targeted delivery of drugs, improved bioavailability, and better therapeutic effectiveness to administer the drug at a constant rate. Polymeric NPs are very small-sized polymeric colloidal elements in which a drug of interest may be encapsulated or incorporated in their polymeric network or conjugated or adsorbed on the layer. Various polymers are employed in the manufacturing of nanoparticles, some of the frequently employed polymers are agents, chitosan, cellulose, gelatin, gliadin, polylactic acid, polylactic-co-glycolic acid, and pullulan. Nanoparticles have been progressively explored for the delivery of targeted ARVs to cells of HIV-infected and have performed the prolonged kinetic release. Drug embedded in this system can give better effectiveness, diminished resistance of drugs, reduction in systemic toxicity and symptoms, and also enhanced patient compliance. The present review highlights the frequently employed manufacturing methods for biodegradable nanoparticles, various polymers used, and its application in anti-retroviral therapy. Also, common evaluation parameters to check the purity of nanoparticles, ongoing and recently concluded clinical trials and patents filled by the various researchers, and the future implication of biodegradable NPs in an innovative drug delivery system are described. The biodegradable NPs are promising systems for the administration of a broad variety of drugs including anti-retroviral drugs, and hence biodegradable nanoparticles can be employed in the future for the treatment of several diseases and disorders.

Pressure-Sensitive Tissue Adhesion and Biodegradation of Viscoelastic Polymer Blends.

Viscoelastic blends of biodegradable polyesters with low and high molecular weight distributions have remarkably strong adhesion (significantly greater than 1 N/cm2) to soft, wet tissue. Those that transition from viscous flow to elastic, solidlike behavior at approximately 1 Hz demonstrate pressure-sensitivity yet also have sufficient elasticity for durable bonding to soft, wet tissue. The pressure-sensitive tissue adhesive (PSTA) blends produce increasingly stronger pull-apart adhesion in response to compressive pressure application, from 10 to 300 s. By incorporating a stiffer high molecular weight component, the PSTA exhibits dramatically improved burst pressure (greater than 100 kPa) when used as a tissue sealant. The PSTA's biodegradation mechanism can be switched from erosion (occurring primarily over the first 10 days) to bulk chemical degradation (and minimal erosion) depending on the chemistry of the high molecular weight component. Interestingly, fibrosis toward the PSTA is reduced when fast-occurring erosion is the dominant biodegradation mechanism.

Tooth Regeneration: Insights from Tooth Development and Spatial-Temporal Control of Bioactive Drug Release.

Tooth defect and tooth loss are common clinical diseases in stomatology. Compared with the traditional oral restoration treatment, tooth regeneration has unique advantages and is currently the focus of oral biomedical research. It is known that dozens of cytokines/growth factors and other bioactive factors are expressed in a spatial-temporal pattern during tooth development. On the other hand, the technology for spatial-temporal control of drug release has been intensively studied and well developed recently, making control release of these bioactive factors mimicking spatial-temporal pattern more feasible than ever for the purpose of tooth regeneration. This article reviews the research progress on the tooth development and discusses the future of tooth regeneration in the context of spatial-temporal release of developmental factors.

Progress in Conductive Polyaniline-Based Nanocomposites for Biomedical Applications: A Review.

Inherently conducting polymers (ICPs) are a specific category of synthetic polymers with distinctive electro-optic properties, which involve conjugated chains with alternating single and double bonds. Polyaniline (PANI), as one of the most well-known ICPs, has outstanding potential applications in biomedicine because of its high electrical conductivity and biocompatibility caused by its hydrophilic nature, low-toxicity, good environmental stability, and nanostructured morphology. Some of the limitations in the use of PANI, such as its low processability and degradability, can be overcome by the preparation of its blends and nanocomposites with various (bio)polymers and nanomaterials, respectively. This review describes the state-of-the-art of biological activities and applications of conductive PANI-based nanocomposites in the biomedical fields, such as antimicrobial therapy, drug delivery, biosensors, nerve regeneration, and tissue engineering. The latest progresses in the biomedical applications of PANI-based nanocomposites are reviewed to provide a background for future research.

Biodegradable Surgical Staple Composed of Magnesium Alloy.

Currently, surgical staples are composed of non-biodegradable titanium (Ti) that can cause allergic reactions and interfere with imaging. This paper proposes a novel biodegradable magnesium (Mg) alloy staple and discusses analyses conducted to evaluate its safety and feasibility. Specifically, finite element analysis revealed that the proposed staple has a suitable stress distribution while stapling and maintaining closure. Further, an immersion test using artificial intestinal juice produced satisfactory biodegradable behavior, mechanical durability, and biocompatibility in vitro. Hydrogen resulting from rapid corrosion of Mg was observed in small quantities only in the first week of immersion, and most staples maintained their shapes until at least the fourth week. Further, the tensile force was maintained for more than a week and was reduced to approximately one-half by the fourth week. In addition, the Mg concentration of the intestinal artificial juice was at a low cytotoxic level. In porcine intestinal anastomoses, the Mg alloy staples caused neither technical failure nor such complications as anastomotic leakage, hematoma, or adhesion. No necrosis or serious inflammation reaction was histopathologically recognized. Thus, the proposed Mg alloy staple offers a promising alternative to Ti alloy staples.

Three-Year Outcomes of Biodegradable Polymer-Coated Ultra-Thin (60 µm) Sirolimus-Eluting Stents in Real-World Clinical Practice.

INTRODUCTION: Although drug-eluting stents (DES) have outclassed the use of bare metal stents, the safety and efficacy of DES at long-term follow-up has still been conflicting because of increased occurrence of late or very late restenosis and stent thrombosis after DES implantation. Hence, the present study was aimed to evaluate the 3-year safety and clinical performance of biodegradable polymer-coated ultra-thin (60 µm) sirolimus-eluting stent (SES) in real-world patients with coronary artery disease (CAD). MATERIALS AND METHODS: This was a physician-initiated, retrospective, single-centre, observational study that included 237 consecutive patients who had previously undergone implantation of only Supraflex SES (Sahajanand Medical Technologies Pvt Ltd, Surat, India) for the treatment of CAD. Follow-up was received after 1 year and 3 years of stent implantation. The primary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction (MI) and target lesion revascularisation (TLR). Stent thrombosis was considered as a safety endpoint. RESULTS: The mean age of patients was 64.1 ± 10.2 years, and 192 (81.0%) patients were male. The average stent length and diameter were 24.4 ± 9.0 mm and 3.1 ± 0.4 mm, respectively. The cumulative MACE rate at 3 years follow-up was 6.5% which included 4 (1.8%) cardiac deaths, 6 (2.8%) MI, and 4 (1.8%) TLR. There were 2 (0.9%) cases of stent thrombosis. CONCLUSION: Treatment of patients with CAD in real-world clinical practice was associated with sustained clinical safety and low rates of restenosis, stent thrombosis and MACE up to 3 years after Supraflex SES implantation.

Biodegradable Magnesium-Incorporated Poly(l-lactic acid) Microspheres for Manipulation of Drug Release and Alleviation of Inflammatory Response.

Poly(l-lactic acid) (PLLA) and magnesium (Mg) are widely concerned biodegradable materials, but during in vivo implantation, the former produces acidic degradation byproducts and can easily induce inflammation in surrounding tissues, whereas the latter is fast corroded and generates alkaline products. The purpose of this study is to develop Mg/PLLA composite microspheres as a novel delivery system, in which Mg particles are used to regulate the drug release profile and suppress PLLA-induced inflammatory response. Morphological observation shows that multiple Mg particles are dispersed both on the surface and in the interior of composite microspheres. In vitro release study indicates that by varying the Mg contents or its particle sizes, the internal connectivity of composite microspheres is changed during hydrolytic degradation, and drug delivery can be facilely manipulated with tunable release patterns. In vivo release study further confirms the feasibility of Mg/PLLA microspheres for tailoring drug release in a physiological environment. The animal experiment reveals that Mg particles can alleviate macrophage infiltration and inflammatory cytokine expression. These results demonstrate the availability of using biodegradable Mg particles to manipulate drug release as well as alleviate PLLA-induced inflammation. The present Mg/PLLA composite microspheres have potential applications in controlled delivery of various therapeutic agents, especially some growth factors, for bone regeneration.

Long-Term Engraftment of Human Cardiomyocytes Combined with Biodegradable Microparticles Induces Heart Repair.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are a promising cell source for cardiac repair after myocardial infarction (MI) because they offer several advantages such as potential to remuscularize infarcted tissue, integration in the host myocardium, and paracrine therapeutic effects. However, cell delivery issues have limited their potential application in clinical practice, showing poor survival and engraftment after transplantation. In this work, we hypothesized that the combination of hiPSC-CMs with microparticles (MPs) could enhance long-term cell survival and retention in the heart and consequently improve cardiac repair. CMs were obtained by differentiation of hiPSCs by small-molecule manipulation of the Wnt pathway and adhered to biomimetic poly(lactic-co-glycolic acid) MPs covered with collagen and poly(d-lysine). The potential of the system to support cell survival was analyzed in vitro, demonstrating a 1.70-fold and 1.99-fold increase in cell survival after 1 and 4 days, respectively. The efficacy of the system was tested in a mouse MI model. Interestingly, 2 months after administration, transplanted hiPSC-CMs could be detected in the peri-infarct area. These cells not only maintained the cardiac phenotype but also showed in vivo maturation and signs of electrical coupling. Importantly, cardiac function was significantly improved, which could be attributed to a paracrine effect of cells. These findings suggest that MPs represent an excellent platform for cell delivery in the field of cardiac repair, which could also be translated into an enhancement of the potential of cell-based therapies in other medical applications.

Tough and Immunosuppressive Titanium-Infiltrated Exoskeleton Matrices for Long-Term Endoskeleton Repair.

Although biodegradable membranes are essential for effective bone repair, severe loss of mechanical stability because of rapid biodegradation, soft tissue invasion, and excessive immune response remain intrinsically problematic. Inspired by the exoskeleton-reinforcing strategy found in nature, we have produced a Ti-infiltrated chitin nanofibrous membrane. The membrane employs vapor-phase infiltration of metals, which often occurs during metal oxide atomic layer deposition (ALD) on organic substrates. This metal infiltration manifests anomalous mechanical improvement and stable integration with chitin without cytotoxicity and immunogenicity. The membrane exhibits both impressive toughness (∼13.3 MJ·m-3) and high tensile strength (∼55.6 MPa), properties that are often mutually exclusive. More importantly, the membrane demonstrates notably enhanced resistance to biodegradation, remaining intact over the course of 12 weeks. It exhibits excellent osteointegrative performance and suppresses the immune response to pathogen-associated molecular pattern molecules indicated by IL-1ß, IL-6, and granulocyte-macrophage colony-stimulating factor expression. We believe the excellent chemico-biological properties achieved with ALD treatment can provide insight for synergistic utilization of the polymers and ALD in medical applications.

In Situ Fabrication of Intelligent Photothermal Indocyanine Green-Alginate Hydrogel for Localized Tumor Ablation.

Simplifying synthesis and administration process, improving photothermal agents' accumulation in tumors, and ensuring excellent biocompatibility and biodegradability are keys to promoting the clinical application of photothermal therapy. However, current photothermal agents have great difficulties in meeting the requirements of clinic drugs from synthesis to administration. Herein, we reported the in situ formation of a Ca2+/Mg2+ stimuli-responsive ICG-alginate hydrogel in vivo for localized tumor photothermal therapy. An ICG-alginate hydrogel can form by the simple introduction of Ca2+/Mg2+ into ICG-alginate solution in vitro, and the widely distributed divalent cations in organization in vivo enabled the in situ fabrication of the ICG-alginate hydrogel without the leakage of any agents by simple injection of ICG-alginate solution into the body of mice. The as-prepared ICG-alginate hydrogel not only owns good photothermal therapy efficacy and excellent biocompatibility but also exhibits strong ICG fixation ability, greatly benefiting the high photothermal agents' accumulation and minimizing the potential side effects induced by the diffusion of ICG to surrounding tissues. The in situ-fabricated ICG-alginate hydrogel was applied successfully in highly efficient PTT in vivo without obvious side effects. Besides, the precursor of the hydrogel, ICG and alginate, can be stored in a stable solid form, and only simple mixing and noninvasive injection are needed to achieve PTT in vivo. The proposed in situ gelation strategy using biocompatible components lays down a simple and mild way for the fabrication of high-performance PTT agents with the superiors in the aspects of synthesis, storage, transportation, and clinic administration.

Biodegradable Polymer-Coated Multifunctional Graphene Quantum Dots for Light-Triggered Synergetic Therapy of Pancreatic Cancer.

In this work, we reported the synthesis of an engineered novel nanocarrier composed of biodegradable charged polyester vectors (BCPVs) and graphene quantum dots (GQDs) for pancreatic cancer (MiaPaCa-2 cells) therapy applications. Such a nanocarrier was utilized to co-load doxorubicin (DOX) and small interfering ribonucleic acid (siRNA), resulting in the formation of GQD/DOX/BCPV/siRNA nanocomplexes. The resulting nanocomplexes have demonstrated high stability in physiologically mimicking media, excellent K-ras downregulation activity, and effective bioactivity inhibition for MiaPaCa-2 cells. More importantly, laser light was used to generate heat for the nanocomplexes via the photothermal effect to damage the cells, which was further employed to trigger the release of payloads from the nanocomplexes. Such triggered release function greatly enhanced the anticancer activity of the nanocomplexes. Preliminary colony formation study also suggested that GQD/DOX/BCPV/siRNA nanocomplexes are qualified carrier candidates in subsequent in vivo tests.

Recent progress in the utilization of biosynthesized polyhydroxyalkanoates for biomedical applications - Review.

PHAs (polyhydroxyalkanoates) have emerged as biodegradable plastics more strongly in the 20th century. A wide range of bacterial species along with fungi, plants, oilseed crops and carbon sources have been used extensively to synthesize PHA on large scales. Alteration of PHA monomers in their structures and composition has led to the development of biodegradable and biocompatible polymers with highly specific mechanical properties. This leads to the incorporation of PHA in numerous biomedical applications within the previous decade. PHAs have been fabricated in various forms to perform tissue engineering to repair liver, bone, cartilage, heart tissues, cardiovascular tissues, bone marrow, and to act as drug delivery system and nerve conduits. A large number of animal trials have been carried out to assess the biomedical properties of PHA monomers, which also confirms the high compatibility of PHA family for this field. This review summarizes the synthesis of PHA from different sources, and biosynthetic pathways and biomedical applications of biosynthesized polyhydroxyalkanoates.

Development of chitosan coated calcium-alginate nanocapsules for oral delivery of liraglutide to diabetic patients.

Chitosan coated calcium-alginate nanocapsules were developed for oral sustained delivery of liraglutide. The effect of coating components including sodium alginate, calcium chloride, and chitosan concentrations on the particle size was studied based on response surface methodology. The beads were characterized by dynamic light scattering, scanning and transmission electron microscopy as well as Fourier transform infrared spectroscopy. It was shown that the diameter of the formed beads was most dependent on the encapsulation technique and alginate concentration. SEM revealed spherical and smooth particles of up to 100 nm diameter for the optimum composition of alginate 0.5%, chitosan 0.5% and calcium chloride 0.5% in the volume ratio of 3:1:1. The resulting bead formulation had a loading efficiency of 92.5% and loading capacity of 54.16%. The nanocapsules exhibited stability of 92.4% and 72.3% over freeze drying and subsequent 60 days storage at 4 °C, respectively. In-vitro release studies in simulated gastrointestinal conditions were carried out in a sequential technique and the amount of drug release was found to be 59.1% after 6 h. The results of this study demonstrated that chitosan coated calcium-alginate nanocapsules hold promise as a potential natural biodegradable polymer-based oral carrier of liraglutide for better management of diabetes.

Combinatorial approaches in post-polymerization modification for rational development of therapeutic delivery systems.

The combinatorial polymer library approach has been proven to be effective for the optimization of therapeutic delivery systems. The library of polymers with chemical diversity has been synthesized by (i) polymerization of functionalized monomers or (ii) post-polymerization modification of reactive polymers. Most scientists have followed the first approach so far, and the second method has emerged as a versatile approach for combinatorial biomaterials discovery. This review focuses on the second approach, especially discussing the post-modifications that employ reactive polymers as templates for combinatorial synthesis of a library of functional polymers with distinct structural diversity or a combination of different functionalities. In this way, the functional polymers have a consistent chain length and distribution, which allows for systematic optimization of therapeutic delivery polymers for the efficient delivery of genes, small-molecule drugs, and protein therapeutics. In this review, the modification of representative reactive polymers for the delivery of different therapeutic payloads are summarized. The recent advances in rational design and optimization of therapeutic delivery systems based on reactive polymers are highlighted. This review ends with a summary of the current achievements and the prospect on future directions in applying the approach of post-polymerization modification of polymers to accelerate the development of therapeutic delivery systems. STATEMENT OF SIGNIFICANCE: A strategy to rationally design and systematically optimize polymers for the efficient delivery of specific therapeutics is highly needed. The combinatorial polymer library approach could be an effective way to this end. The post-polymerization modification of reactive polymer precursors is applicable for the combinatorial synthesis of a library of functional polymers with distinct structural diversity across a consistent degree of polymerization. This allows for parallel comparison and systematic evaluation/optimization of functional polymers for efficient therapeutic delivery. This review summarizes the key elements of this combinatorial polymer synthesis approach realized by post-polymerization modification of reactive polymer precursors towards the development and identification of optimal polymers for the efficient delivery of therapeutic agents.

Biodegradable 3D printed polymer microneedles for transdermal drug delivery.

Biodegradable polymer microneedle (MN) arrays are an emerging class of transdermal drug delivery devices that promise a painless and sanitary alternative to syringes; however, prototyping bespoke needle architectures is expensive and requires production of new master templates. Here, we present a new microfabrication technique for MNs using fused deposition modeling (FDM) 3D printing using polylactic acid, an FDA approved, renewable, biodegradable, thermoplastic material. We show how this natural degradability can be exploited to overcome a key challenge of FDM 3D printing, in particular the low resolution of these printers. We improved the feature size of the printed parts significantly by developing a post fabrication chemical etching protocol, which allowed us to access tip sizes as small as 1 µm. With 3D modeling software, various MN shapes were designed and printed rapidly with custom needle density, length, and shape. Scanning electron microscopy confirmed that our method resulted in needle tip sizes in the range of 1-55 µm, which could successfully penetrate and break off into porcine skin. We have also shown that these MNs have comparable mechanical strengths to currently fabricated MNs and we further demonstrated how the swellability of PLA can be exploited to load small molecule drugs and how its degradability in skin can release those small molecules over time.