Udayabhanu Jammalamadaka

Antibiotic and chemotherapeutic enhanced three-dimensional printer filaments and constructs for biomedical applications

Three-dimensional (3D) printing and additive manufacturing holds potential for highly personalized medicine, and its introduction into clinical medicine will have many implications for patient care. This paper demonstrates the first application of 3D printing as a method for the potential sustained delivery of antibiotic and chemotherapeutic drugs from constructs for patient treatment. Our design is focused on the on-demand production of anti-infective and chemotherapeutic filaments that can be used to create discs, beads, catheters, or any medical construct using a 3D printing system. The design parameters for this project were to create a system that could be modularly loaded with bioactive agents. All 3D-printed constructs were loaded with either gentamicin or methotrexate and were optimized for efficient and extended antibacterial and cancer growth-inhibiting cytostatic activity. Preliminary results demonstrate that combining gentamicin and methotrexate with polylactic acid forms a composite possessing a superior combination of strength, versatility, and enhanced drug delivery. Antibacterial effects and a reduction in proliferation of osteosarcoma cells were observed with all constructs, attesting to the technical and clinical viability of our composites. In this study, 3D constructs were loaded with gentamicin and methotrexate, but the method can be extended to many other drugs. This method could permit clinicians to provide customized and tailored treatment that allows patient-specific treatment of disease and has significant potential for use as a tunable drug delivery system with sustained-release capacity for an array of biomedical applications.

Three-dimensional printing of bioactive hernia meshes: In vitro proof of principle

THREE-DIMENSIONAL (3-D) printing of operative instruments, prostheses, and implants is a topic of considerable interest in both scientific literature and popular media. Surgical meshes are widely used in hernia repair and may be a candidate for specialized 3-D printing. On-demand, intraoperative 3-D printing of surgical meshes has the potential to facilitate patient-specific medicine. Synthetic and biologic meshes come in many different commercial forms. In hernia repair, these prefabricated meshes often require modification to match patient-specific anatomy. 3-D printing of meshes tailored to intraoperative measurements, patient anatomy, specific situations, and patient comorbidities could improve technical facility, decrease waste, and may even save costs. 3-D-printedmeshes can be fabricated in real time using biocompatible, permanent, or absorbable material alone or in combination. Mesh size, shape, material, distribution of grommets/rivets, thickness, and flexibility can be customized with 3-D printing and allow reinforced areas to be created as suture points. Mesh pore size or weave can also be modified. In addition, 3-D-printed meshes can be used as a depot for localizeddrugdelivery, achieving therapeutic local levels while avoiding systemic toxicity. Previous work has demonstrated the

Recent Advances in Biomaterials for 3D Printing and Tissue Engineering

Three-dimensional printing has significant potential as a fabrication method in creating scaffolds for tissue engineering. The applications of 3D printing in the field of regenerative medicine and tissue engineering are limited by the variety of biomaterials that can be used in this technology. Many researchers have developed novel biomaterials and compositions to enable their use in 3D printing methods. The advantages of fabricating scaffolds using 3D printing are numerous, including the ability to create complex geometries, porosities, co-culture of multiple cells, and incorporate growth factors. In this review, recently-developed biomaterials for different tissues are discussed. Biomaterials used in 3D printing are categorized into ceramics, polymers, and composites. Due to the nature of 3D printing methods, most of the ceramics are combined with polymers to enhance their printability. Polymer-based biomaterials are 3D printed mostly using extrusion-based printing and have a broader range of applications in regenerative medicine. The goal of tissue engineering is to fabricate functional and viable organs and, to achieve this, multiple biomaterials and fabrication methods need to be researched.

Performance evaluation of nanoclay enriched anti-microbial hydrogels for biomedical applications

A major factor contributing to the failure of orthopedic and orthodontic implants is post-surgical infection. Coating metallic implant surfaces with anti-microbial agents has shown promise but does not always prevent the formation of bacterial biofilms. Furthermore, breakdown of these coatings within the human body can cause release of the anti-microbial drugs in an uncontrolled or unpredictable fashion. In this study, we used a calcium alginate and calcium phosphate cement (CPC) hydrogel composite as the base material and enriched these hydrogels with the anti-microbial drug, gentamicin sulfate, loaded within a halloysite nanotubes (HNTs). Our results demonstrate a sustained and extended release of gentamicin from hydrogels enriched with the gentamicin-loaded HNTs. When tested against the gram-negative bacteria, the hydrogel/nanoclay composites showed a pronounced zone of inhibition suggesting that anti-microbial doped nanoclay enriched hydrogels can prevent the growth of bacteria. The release of gentamicin sulfate for a period of five days from the nanoclay-enriched hydrogels would supply anti-microbial agents in a sustained and controlled manner and assist in preventing microbial growth and biofilm formation on the titanium implant surface. A pilot study, using mouse osteoblasts, confirmed that the nanoclay enriched surfaces are also cell supportive as osteoblasts readily, proliferated and produced a type I collagen and proteoglycan matrix.

Medication eluting devices for the field of OBGYN (MEDOBGYN): 3D printed biodegradable hormone eluting constructs, a proof of concept study

3D printing has the potential to deliver personalized implants and devices for obstetric and gynecologic applications. The aim of this study is to engineer customizable and biodegradable 3D printed implant materials that can elute estrogen and/or progesterone. All 3D constructs were printed using polycaprolactone (PCL) biodegradable polymer laden with estrogen or progesterone and were subjected to hormone-release profile studies using ELISA kits. Material thermal properties were tested using thermogravimetric analysis and differential scanning calorimetry. The 3D printed constructs showed extended hormonal release over a one week period. Cytocompatibility and bioactivity were assessed using a luciferase assay. The hormone-laden 3D printed constructs demonstrated an increase in luciferase activity and without any deleterious effects. Thermal properties of the PCL and hormones showed degradation temperatures above that of the temperature used in the additive manufacturing process–suggesting that 3D printing can be achieved below the degradation temperatures of the hormones. Sample constructs in the shape of surgical meshes, subdermal rods, intrauterine devices and pessaries were designed and printed. 3D printing of estrogen and progesterone-eluting constructs was feasible in this proof of concept study. These custom designs have the potential to act as a form of personalized medicine for drug delivery and optimized fit based on patient-specific anatomy.

Novel Biomaterials Used in Medical 3D Printing Techniques

The success of an implant depends on the type of biomaterial used for its fabrication. An ideal implant material should be biocompatible, inert, mechanically durable, and easily moldable. The ability to build patient specific implants incorporated with bioactive drugs, cells, and proteins has made 3D printing technology revolutionary in medical and pharmaceutical fields. A vast variety of biomaterials are currently being used in medical 3D printing, including metals, ceramics, polymers, and composites. With continuous research and progress in biomaterials used in 3D printing, there has been a rapid growth in applications of 3D printing in manufacturing customized implants, prostheses, drug delivery devices, and 3D scaffolds for tissue engineering and regenerative medicine. The current review focuses on the novel biomaterials used in variety of 3D printing technologies for clinical applications. Most common types of medical 3D printing technologies, including fused deposition modeling, extrusion based bioprinting, inkjet, and polyjet printing techniques, their clinical applications, different types of biomaterials currently used by researchers, and key limitations are discussed in detail.

Osteoinductive Calcium Phosphate clay nanoparticle bone cements (CPCs) with enhanced mechanical properties

Calcium Phosphate Cements (CPCs) with osteoconductive properties are limited in their applications because of their poor mechanical properties. This study investigated the additive effect of Dexamethasone-doped Halloysite Nanotubes (HNTs on the mechanical properties of CPCs. HNTs are nanosized tubes with alumino-silicate composition. Physico-chemical properties, cytocompatability and cellular functionality of the nanocomposites were assayed. Results suggest that these nanoenhanced composites have a huge potential to broaden the applications of CPCs.

Doped Halloysite Nanotubes for Use in the 3D Printing of Medical Devices

Previous studies have established halloysite nanotubes (HNTs) as viable nanocontainers capable of sustained release of a variety of antibiotics, corrosion agents, chemotherapeutics and growth factors either from their lumen or in outer surface coatings. Accordingly, halloysite nanotubes (HNTs) hold great promise as drug delivery carriers in the fields of pharmaceutical science and regenerative medicine. This study explored the potential of 3D printing drug doped HNT constructs. We used a model drug, gentamicin (GS) and polylactic acid (PLA) to fabricate GS releasing disks, beads, and pellets. Gentamicin was released from 3D printed constructs in a sustained manner and had a superior anti-bacterial growth inhibition effect that was dependent on GS doping concentration. While this study focused on a model drug, gentamicin, combination therapy is possible through the fabrication of medical devices containing HNTs doped with a suite of antibiotics or antifungals. Furthermore, tailored dosage levels, suites of antimicrobials, delivered locally would reduce the toxicity of individual agents, prevent the emergence of resistant strains, and enable the treatment of mixed infections.

Design and evaluation of a nanoenhanced anti-infective calcium phosphate bone cements.

Post-operative complications due to infections are the most common problems that occur following dental and orthopedic implant surgeries and bone repair procedures. Preventing post-surgical infections is therefore a critical need that current polymethylmethacrylate (PMMA) bone cement fail to address. Calcium phosphate cements (CPCs) are unique in their ability to crystallize calcium and phosphate salts into hydroxyapatite (HA) and hence is naturally osteoconductive. Due to its low mechanical strength its use in implant fixation and bone repair is limited to non-load bearing applications. The present work describes a new and novel antibiotic-doped clay nanotube CPC composite with enhanced mechanical properties as well as sustained release properties.

Formulation and Evaluation of Nanoenhanced Anti-bacterial Calcium Phosphate Bone Cements

Post-operative complications due to infections are the most common problems that occur following dental and orthopedic implant surgeries and bone repair procedures. Blood samples randomly collected from postmortem donors showed a 26% bacterial contamination rate. Preventing post-surgical infections is therefore a critical need that current polymethyl methacrylate bone cements fail to address. Current clinical practice uses direct impregnation of antibiotics in the bone cement mixture and applying the antibiotic-laden cement to the implant or fracture site. However, the addition of antibiotics results in reduced mechanical properties in the bone cement. Furthermore, the release of the antibiotic is short-lived and results in less than maximal antibiotic release. Calcium phosphate cements are unique in their ability to crystallize calcium and phosphate salt into hydroxyapatite and hence are naturally osteoconductive. Due to its low mechanical strength, its use in implant fixation, bone grafts and bone repair is limited to non-load bearing applications. The present work employs clay nanotubes as a means for developing enhanced mechanical properties in calcium phosphate cements as well as the sustained release of gentamicin and neomycin, two commonly used antibiotics.