Bacteria Invade the Brain Following Sterile Intracortical Microelectrode Implantation.

Brain-machine interface performance is largely affected by the neuroinflammatory responses resulting in large part from blood-brain barrier (BBB) damage following intracortical microelectrode implantation. Recent findings strongly suggest that certain gut bacterial constituents penetrate the BBB and are resident in various brain regions of rodents and humans, both in health and disease. Therefore, we hypothesized that damage to the BBB caused by microelectrode implantation could amplify dysregulation of the microbiome-gut-brain axis.

Polymerized cyclodextrin microparticles for sustained antibiotic delivery in lung infections.

Pulmonary infections complicate chronic lung diseases requiring attention to both the pathophysiology and complexity associated with infection management. Patients with cystic fibrosis (CF) struggle with continuous bouts of pulmonary infections, contributing to lung destruction and eventual mortality. Additionally, CF patients struggle with airways that are highly viscous, with accumulated mucus creating optimal environments for bacteria colonization.

Grafting of short elastin-like peptides using an electric field.

Surface-grafted elastin has found a wide range of uses such as sensing, tissue engineering and capture/release applications because of its ability to undergo stimuli-responsive phase transition. While various methods exist to control surface grafting in general, it is still difficult to control orientation as attachment occurs. This study investigates using an electric field as a new approach to control the surface-grafting of short elastin-like polypeptide (ELP).

Polymer Additives to Personal Protective Equipment can Inactivate Pathogens.

Face masks have been proven to be medicine's best public health tool for preventing transmission of airborne pathogens. However, in situations with continuous exposure, lower quality and "do-it-yourself" face masks cannot provide adequate protection against pathogens, especially when mishandled. In addition, the use of multiple face masks each day places a strain on personal protective equipment (PPE) supply and is not environmentally sustainable.

Leveraging Affinity Interactions to Prolong Drug Delivery of Protein Therapeutics.

While peptide and protein therapeutics have made tremendous advances in clinical treatments over the past few decades, they have been largely hindered by their ability to be effectively delivered to patients. While bolus parenteral injections have become standard clinical practice, they are insufficient to treat diseases that require sustained, local release of therapeutics. Cyclodextrin-based polymers (pCD) have been utilized as a platform to extend the local delivery of small-molecule hydrophobic drugs by leveraging hydrophobic-driven thermodynamic interactions between pCD and payload to extend its release, which has seen success both in vitro and in vivo.

Injectable Extracellular Matrix Microparticles Promote Heart Regeneration in Mice with Post-ischemic Heart Injury.

Ischemic heart injury causes permanent cardiomyocyte loss and fibrosis impairing cardiac function. Tissue derived biomaterials have shown promise as an injectable treatment for the post-ischemic heart. Specifically, decellularized extracellular matrix (dECM) is a protein rich suspension that forms a therapeutic hydrogel once injected and improves the heart post-injury response in rodents and pig models.

PMMA Bone Cement Composite Functions as an Adjuvant Chemotherapeutic Platform for Localized and Multi-Window Release during Bone Reconstruction.

Primary bone tumor resections often result in critical size defects, which then necessitate challenging clinical management approaches to reconstruct. One such intervention is the Masquelet technique, in which poly(methyl methacrylate) (PMMA) bone cement is placed as a spacer temporarily while adjuvant chemotherapeutics are administered systemically. The spacer is later removed and replaced with bone autograft.

Polymer Microparticles Prolong Delivery of the 15-PGDH Inhibitor SW033291.

As the prevalence of age-related fibrotic diseases continues to increase, novel antifibrotic therapies are emerging to address clinical needs. However, many novel therapeutics for managing chronic fibrosis are small-molecule drugs that require frequent dosing to attain effective concentrations. Although bolus parenteral administrations have become standard clinical practice, an extended delivery platform would achieve steady-state concentrations over a longer time period with fewer administrations.

Recent Advances in the Evaluation of Antimicrobial Materials for Resolution of Orthopedic Implant-Associated Infections .

While orthopedic implant-associated infections are rare, revision surgeries resulting from infections incur considerable healthcare costs and represent a substantial research area clinically, in academia, and in industry. In recent years, there have been numerous advances in the development of antimicrobial strategies for the prevention and treatment of orthopedic implant-associated infections which offer promise to improve the limitations of existing delivery systems through local and controlled release of antimicrobial agents. Prior to translation to orthopedic implant-associated infection models, the properties (, degradation, antimicrobial activity, biocompatibility) of the antimicrobial materials can be evaluated in subcutaneous implant models.

Characterization of Inflammatory and Fibrotic Encapsulation Responses of Implanted Materials with Bacterial Infection.

Medical device infections are costly, while preclinical assessment of antimicrobial properties for new materials is time intensive and imperfect at capturing the interrelated aspects of infection response and wound resolution. Herein, we developed an in vivo model for quantification of inflammatory and biocompatibility responses in the presence of a sustained implant-associated infection. The antimicrobial effectiveness of commercially available polymer materials was compared to that of thermoplastic polyurethane (TPU) materials modified with putative antimicrobial strategies as example test materials.

Ultrasound Triggered Drug Release from Affinity-Based β-Cyclodextrin Polymers for Infection Control.

This work demonstrates a slow, sustained drug delivery system that provides on-demand delivery bursts through the application of pulsed therapeutic ultrasound (TUS). Insoluble β-cyclodextrin-polymer (pCD) disks were loaded with a saturated antibiotic solution of rifampicin (RIF) and used for drug delivery studies. To obtain on-demand release from the implants, TUS was applied at an intensity of 1.

Machine learning and big data provide crucial insight for future biomaterials discovery and research.

Machine learning have been widely adopted in a variety of fields including engineering, science, and medicine revolutionizing how data is collected, used, and stored. Their implementation has led to a drastic increase in the number of computational models for the prediction of various numerical, categorical, or association events given input variables. We aim to examine recent advances in the use of machine learning when applied to the biomaterial field.

Modified Cyclodextrin Microparticles to Improve PMMA Drug Delivery Without Mechanical Loss.

Antibiotic-loaded poly(methyl methacrylate) (PMMA) cement is commonly used as a local delivery system to treat and prevent orthopedic infections associated with arthroplasties in load-bearing applications. However, these delivery systems are inefficient as release rate sharply declines to subinhibitory levels. Prior studies have shown that by adding in drug-filled cyclodextrin (CD) microparticles into PMMA cement, a more consistent release is observed, and antibiotic refilling through simulated implantation can be achieved.

Poly(methyl methacrylate) Bone Cement Composite Can Be Refilled with Antibiotics after Implantation in Femur or Soft Tissue.

While periprosthetic joint infections (PJIs) result in a small percentage of patients following arthroplasties, they are challenging to treat if they spread into bone and soft tissue. Treatment involves delivering antibiotics using poly(methyl methacrylate) (PMMA) bone cement. However, antibiotic release is insufficient for prolonged infections.

Antibiotic Refilling, Antimicrobial Activity, and Mechanical Strength of PMMA Bone Cement Composites Critically Depend on the Processing Technique.

Antibiotic-laden poly(methyl methacrylate) (PMMA) bone cement is used in a variety of applications including temporary spacers for load-bearing arthroplasties and non-load bearing orthopedic revision procedures and antibiotic beads to treat infections. Depending upon the surgical preparation technique, properties of PMMA can widely vary. The primary objective of this work was to perform an in-depth structure-function analysis regarding how processing of PMMA impacted material and structural properties (i.

Periadventitial Delivery of Simvastatin-Loaded Microparticles Attenuate Venous Neointimal Hyperplasia Associated With Arteriovenous Fistula.

Background Venous neointimal hyperplasia and venous stenosis (VS) formation can result in a decrease in arteriovenous fistula (AVF) patency in patients with end-stage renal disease. There are limited therapies that prevent VNH/VS. Systemic delivery of simvastatin has been shown to reduce VNH/VS but local delivery may help decrease the side effects associated with statin use.

A Polymeric Delivery System Enables Controlled Release of Genipin for Spatially-Confined In Situ Crosslinking of Injured Connective Tissues.

An emerging approach toward repair of connective tissues applies exogenous crosslinkers to mechanically augment injured structures in vivo. One crosslinker that has been explored for this purpose is the plant-derived small molecule genipin. However, genipin's high reactivity to primary amines in proteins, small size, and high diffusion coefficient necessitate localizing and controlling its delivery to avoid off-target or adverse effects.

Affinity-Based Polymers Provide Long-Term Immunotherapeutic Drug Delivery Across Particle Size Ranges Optimal for Macrophage Targeting.

Drug delivery to specific arms of the immune system can be technically challenging to provide prolonged drug release while limiting off-target toxicity given the limitations of current drug delivery systems. In this work, we test the design of a cyclodextrin (CD) polymer platform to extend immunomodulatory drug delivery via affinity interactions for sustained release at multiple size scales. The parameter space of synthesis variables influencing particle nucleation and growth (pre-incubation time and stirring speed) and post-synthesis grinding effects on resulting particle diameter were characterized.

Nonthermal plasma treatment of polymers modulates biological fouling but can cause material embrittlement.

Plasma-based treatment is a prevalent strategy to alter biological response and enhance biomaterial coating quality at the surfaces of biomedical devices and implants, especially polymeric materials. Plasma, an ionized gas, is often thought to have negligible effects on the bulk properties of prosthetic substrates given that it alters the surface chemistry on only the outermost few nanometers of material. However, no studies to date have systematically explored the effects of plasma exposure on both the surface and bulk properties of a biomaterial.

Engineering selective molecular tethers to enhance suboptimal drug properties.

Small-molecule drugs are utilized in a wide variety of clinical applications, however, many of these drugs suffer from one or more suboptimal properties that can hinder its delivery or cellular action in vivo, or even shelf an otherwise biologically tolerable drug. While high-throughput screening provides a method to discover drugs with altered chemical properties, directly engineering small-molecule bioconjugates provides an opportunity to specifically modulate drug properties rather than sifting through large drug libraries with seemingly 'random' drug properties. Herein, we propose that selectively "tethering" a drug molecule to an additional group with favorable properties will improve the drug conjugate's overall properties, such as solubility.

Resveratrol Delivery from Implanted Cyclodextrin Polymers Provides Sustained Antioxidant Effect on Implanted Neural Probes.

Intracortical microelectrodes are valuable tools used to study and treat neurological diseases. Due in large part to the oxidative stress and inflammatory response occurring after electrode implantation, the signal quality of these electrodes decreases over time. To alleviate this response, resveratrol, a natural antioxidant which elicits neuroprotective effects through reduction of oxidative stress, was utilized.

Elucidating the Structure-Function Relationship of Solvent and Cross-Linker on Affinity-Based Release from Cyclodextrin Hydrogels.

Minocycline (MNC) is a tetracycline antibiotic capable of associating with cyclodextrin (CD), and it is a frontline drug for many instances of implant infection. Due to its broad-spectrum activity and long half-life, MNC represents an ideal drug for localized delivery; however, classic polymer formulations, particularly hydrogels, result in biphasic release less suitable for sustained anti-microbial action. A polymer delivery system capable of sustained, steady drug delivery rates poses an attractive target to maximize the antimicrobial activity of MNC.

Affinity Effects on the Release of Non-Conventional Antifibrotics from Polymer Depots.

For many chronic fibrotic conditions, there is a need for local, sustained antifibrotic drug delivery. A recent trend in the pharmaceutical industry is the repurposing of approved drugs. This paper investigates drugs that are classically used for anthelmintic activity (pyrvinium pamoate (PYR)), inhibition of adrenal steroidgenesis (metyrapone (MTP)), bactericidal effect (rifampicin (RIF), and treating iron/aluminum toxicity (deferoxamine mesylate (DFOA)), but are also under investigation for their potential positive effect in wound healing.

Repurposing biodegradable tissue engineering scaffolds for localized chemotherapeutic delivery.

While highly porous biodegradable sponges have typically been used as tissue engineering scaffolds, they could be applicable in settings requiring drug delivery. Since most drug delivery devices are intentionally solid, nonporous polymers, a detailed structure-function relationship of delivery from a porous degradable sponges would allow researchers to develop such devices for either delivery alone, or in conjunction with tissue engineering. Two fabrication techniques (salt-leaching and solvent-quenching) were used to prepare several different variations of poly(DL-lactide-glycolide) and poly(caprolactone)-co-poly(lactide) porous sponges.

Combination Antibiotic Delivery in PMMA Provides Sustained Broad-Spectrum Antimicrobial Activity and Allows for Postimplantation Refilling.

Antibiotics are commonly added to poly(methyl methacrylate) (PMMA) by surgeons to locally treat infections such as in bone cement for joint replacement surgeries, as well as implantable antimicrobial "beads". However, this strategy is of limited value in high-risk patients where infections can be recurrent or chronic and otherwise hard to treat. Also, when only one drug is incorporated and applied toward polymicrobial infections (multiple bacterial species), there is a high risk that bacteria can develop antibiotic resistance.