Polymers highlighted evidence from existing studies that support the use of natural-based bioinks
3D Printing Applications in the World of Pharmacy
3D printing offers cost-effective and rapid creation of diverse shapes that have many applications in our lives. Recently, attention has shifted to patient-centric drug development, with 3D printing becoming a key player in the pharmaceutical field.
Compared to traditional methods, 3D printing provides amazing flexibility for producing customizable medications tailored to individual patient needs. This technology operates by depositing layers of materials using computer-aided design (CAD) software or 3D scanners. Various 3D printing technologies, such as laser-based, inkjet-based, and extrusion-based systems, are employed based on factors like resolution, biocompatibility, temperature, and cost-effectiveness.
The impact of 3D printing on pharmaceuticals is profound, allowing for the precise fabrication of diverse pharmaceutical systems and devices. Experts foresee a shift towards personalized medicine, departing from the one-size-fits-all approach. However, achieving high-quality dosage forms requires meticulous attention to printing parameters and an in-depth understanding of materials' characteristics.
As 3D printing evolves, business models involving the sale of 3D-printed products are emerging. The integration of 3D printers in pharmacies and hospitals is anticipated as regulatory guidelines are established, enabling quality-by-design printing of pharmaceutical forms.
In biomaterials, the use of inks or bioinks is crucial. Natural biomaterials like alginates and synthetic biopolymers enhance the resolution of 3D-printed objects. The diversity of biopolymers and APIs makes 3D printing promising for constructing various drug delivery systems, contributing to effective wound healing. While Inkjet-based systems offer precise printing for tissue engineering. Extrusion-based 3D printing allows for scaffolds and microneedles, with the choice depending on the intended application and polymer properties.
Natural polymers like pectin and pluronic F-127 show efficacy in extrusion-based 3D printing for wound healing. Thermoresponsive hydrogels, including nanocellulose, introduce optimal rheological characteristics for extrusion-based printing, leading to the development of 4D printing.
Oral Drug Delivery Devices (ODDDs) like tablets and capsules are widely used for their rapid release profiles, but traditional methods limit design flexibility and often result in a "one-dose-fits-all" approach due to high costs and potential drug interactions. A study done in 1999 explored 3D printing for ODDDs, showcasing the ability to tailor release mechanisms. Binder Jetting has since gained approval for the first 3D printed drug, Spritam®, in 2016.
Material Jetting (MJ) and filament extrusion techniques have also been employed for ODDDs, allowing for the creation of tablets with various release profiles. Topical drug delivery through 3D printing has improved drug loading and accuracy in masks and wound dressings compared to traditional methods. Personalized 3D-printed masks for facial hypertrophic scars have been developed.
For rectal and vaginal drug delivery, 3D printing methods such as SLA and filament extrusion have been utilized to create customizable geometries for suppositories and intrauterine system (IUS) devices. In parenteral drug delivery, 3D printing has been used to create microneedles for rapid drug action and implantable devices like stents and catheters.
While the future of 3D printing in drug delivery holds significant potential, challenges include ensuring quality control, safety, and regulatory compliance, with limited guidance available. Large-scale manufacturing and collaboration among academia, industry, and government are crucial for widespread adoption. Machine learning (ML) is emerging as a tool to optimize design parameters and predict 3D printing performance, contributing to enhanced product quality and productivity.
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Advancements in 3D Printing and Wound Healing
Wounds, both acute and chronic, pose a considerable health risk on a global scale, affecting the lives of millions. As wounds pass a certain size, they often become challenging to self-heal, leading to chronic conditions and, in severe cases, mortality. Recent advancements in 3D printing technology, in conjunction with biocompatible hydrogels, offer a promising route for the development of intelligent wound dressings. These dressings, made through 3D printing, can incorporate antibiotics, antibacterial nanoparticles, and drugs to expedite the wound healing process. The precise control from 3D printing technology enables the production of customized dressings, addressing various challenges in wound care.
The prevalence of chronic wounds globally emphasizes the need for innovative solutions. Traditional wound dressings, while commonly used, often show limitations such as poor adherence to newly grown tissues and low oxygen permeability. Modern wound dressings, especially those using 3D printing technology and biocompatible hydrogels, are multifunctional. They provide enhanced physical protection, maintain optimal wound microenvironment moisture, and accelerate the healing process.
Recent studies on hydrogel-based wound dressings produced through 3D printing have showcased significant progress. Works include advancements in creating physically cross-linked chitosan hydrogels, developments in composite hydrogels for biomedical applications, and a focus on 3D-printed conductive hydrogels. The versatility of 3D printing extends to printing polysaccharides and proteins, contributing to various fields such as drug delivery and regenerative medicine.
Hydrogels are characterized by their three-dimensional crosslinked structure and water-absorbing properties. Natural hydrogels, including chitosan and alginate, show biocompatibility but may trigger immune responses. On the other hand, synthetic hydrogels offer reproducibility but lack inherent bioactivity. Smart hydrogels, responsive to stimuli like temperature, pH, and biological molecules, emerge as a promising avenue for wound care.
Smart hydrogel wound dressings, responsive to stimuli and capable of maintaining an optimal wound environment, play an important role in the wound healing process. These dressings enhance oxygen permeability, efficiently absorb exudate, and contribute to the various phases of wound healing, including hemostasis, inflammation, tissue growth, and tissue remodeling.
The mechanical strength and water absorption of hydrogel-based wound dressings play a crucial role in their effectiveness. The cross-linking process significantly influences these properties. Typically, hydrogels contain 5 to 10% crosslinking polymers, and the crosslinking ratio affects the swelling and strength of the hydrogel. More crosslinking results in less swelling but higher strength. However, excessive crosslinking can make the material rigid or glassy.
The type of crosslinker used is essential, with physical and chemical crosslinkers being the two main categories. Physical crosslinkers are formed by weak interactions, acting as bridges between polymer bonds. Chemical crosslinkers, on the other hand, involve covalent bonds that are more challenging to degrade. The choice of crosslinking method influences the overall performance of the hydrogel wound dressing.
Different types of crosslinking, such as semi-IPN and double network (DN) hydrogels, offer unique characteristics. Semi-IPN hydrogels effectively respond to pH or temperature changes, possess modified pore size, and enable slow drug release. DN hydrogels, comprising two networks with distinct structures, exhibit lower water absorption rates but higher mechanical strength and toughness. The sacrificial bonds in the first network sustain stress, while the second network's ductile polymer chain can extend to sustain large deformation.
Moving on to additive manufacturing and 3D printing, these technologies have gained popularity in recent years. Various techniques like fused deposition modeling (FDM), stereolithography (SLA), polyjet process, selective laser sintering (SLS), 3D inkjet, and digital light processing (DLP) have different characteristics, impacting repeatability, resolution, printing time, and material processing capabilities. Each technique has its compromise in terms of material properties and application suitability.
3D printing offers advantages over traditional methods, such as reduced steps, less manual labor, quick production, low waste generation, and risk mitigation. In wound dressing applications, 3D printing, especially techniques like DLP and STL, has shown promising outcomes. These methods can process biocompatible polymer materials like hydrogels, mimicking the extracellular matrix (ECM) of the skin. However, challenges such as printing large structures with good mechanical properties and addressing surface finish issues persist.
Bioprinting, a subset of 3D printing, holds promise in burn treatment. It involves layer-by-layer deposition of cells and scaffolding materials over burn injuries, aiming for optimal esthetic outcomes and improved scar quality. Bioprinting-based wound dressings go beyond traditional dressings by promoting wound closure and enhancing functional outcomes.
While 3D printing of hydrogels for wound dressings has shown significant progress, challenges remain. Issues like adhesion, applicability to various body parts, and addressing technical limitations during the pre-printing, printing, and maturation stages need further attention.
Moving to recent developments, various hydrogel wound dressings incorporating 3D printing technologies have been explored. The integration of sensors with these dressings has emerged as a cutting-edge approach. Biosensors, when integrated into wound dressings, offer advantages such as real-time sensing, response to changes in the wound environment, and remote monitoring. Temperature and pH sensors have been commonly integrated, providing valuable insights into infection and inflammation.
When the skin is injured, its pH shifts from acidic to alkaline. The skin's acidic pH range (4–6) is vital for pathogen defense, sourced from sebaceous gland fatty acids and sweat's lactic and amino acids. Wound pH evolves from alkaline to neutral and then acidic during healing. Transducers track pH-responsive hydrogel volumetric changes through mechanical work or property alterations.
Various studies utilize pH indicators like phenol red or red cabbage to detect pH changes in hydrogel patches. The transparency of the hydrogel enables naked-eye pH level observation. However, water content and calcium content can affect these pH indicators making it a difficult option. Integrated pH sensors in wound dressings provide continuous, real-time monitoring without physical contact. Smart patches with microchips for ion tracking and drug release, compatible with smartphones, exemplify this advancement. Reinforcing hydrogels with nanomaterials enhances their properties, allowing for diverse sensor integration. However, dressings must align with skin movement, deform as wounds heal, and not impede clotting.
Despite the promising potential of wound bandage-integrated sensors, challenges remain in the current landscape. 3D-printed hydrogel-based wound dressings have shown promise but face challenges such as poor mechanical strength and stability. Stereolithographic techniques often result in parts with inconvenient mechanical properties, and resin homogeneity can be a concern. Overcoming these challenges may involve post-curing processes and the incorporation of specific additives, such as gluconic acid, to stabilize pH levels and prevent bacterial growth.
Nanofillers and cations like calcium ions play crucial roles in enhancing hydrogel properties. Carbon nanomaterials, when combined with hydrogels, show potential in drug delivery applications, although concerns about toxicity remain. Cations like K+ and Ca2+ contribute to the mechanical strength of printed hydrogels and can be employed for various functionalities, including pressure sensing. Overcoming current limitations and addressing challenges will pave the way for more effective and patient-friendly wound care solutions in the future.
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