Reduced Sliding Friction of Lubricant-Impregnated Catheters.

During urethral catheterization, sliding friction can cause discomfort and even hemorrhaging. In this report, we use a lubricant-impregnated polydimethylsiloxane coating to reduce the sliding friction of a catheter. Using a pig urethra attached to a microforce testing system, we found that a lubricant-impregnated catheter reduces the sliding friction during insertion by more than a factor of two. This suggests that slippery, lubricant-impregnated surfaces have the potential to enhance patient comfort and safety during catheterization.

Stability of Aerosolized SARS-CoV-2 on Masks and Transfer to Skin.

The potential for masks to act as fomites in the transmission of SARS-CoV-2 has been suggested but not demonstrated experimentally or observationally. In this study, we aerosolized a suspension of SARS-CoV-2 in saliva and used a vacuum pump to pull the aerosol through six different types of masks. After 1 h at 28 °C and 80% RH, SARS-CoV-2 infectivity was not detectable on an N95 and surgical mask, was reduced by 0.7 log10 on a nylon/spandex mask, and was unchanged on a polyester mask and two different cotton masks when recovered by elution in a buffer. SARS-CoV-2 RNA remained stable for 1 h on all masks. We pressed artificial skin against the contaminated masks and detected the transfer of viral RNA but no infectious virus to the skin. The potential for masks contaminated with SARS-CoV-2 in aerosols to act as fomites appears to be less than indicated by studies involving SARS-CoV-2 in very large droplets.

Developing Echogenic Materials as Catheters for Use with Ultrasound.

Patients with peripherally inserted central catheters (PICCs) are routinely discharged with the catheters in place. These patients experience complications due to undetected thrombosis or accidental dislodgement, with tracking through limited X-ray imaging. Developing catheters with the capability to be tracked without the need for X-ray imaging would greatly benefit these patients by decreasing patient stress, reducing time to diagnosis, and increasing nursing home capabilities. This study reports on the incorporation of echogenic microspheres into catheters to produce bulk echogenic effects for developments in the field of real-time ultrasound tracking of polymeric medical devices. The impact on elastic modulus, ultrasound contrast, and cytocompatibility of the polymer was analyzed when incorporating up to 10 wt % glass microspheres. Up to this loading level, the elastic modulus was found to remain constant. However, at 10 wt %, extrusion defects due to agglomeration, air bubbles, and shearing were numerous and deemed detrimental to ultrasound imaging. Successful, defect-free samples were produced with 5 wt % microsphere loading and when embedded in a soft tissue phantom revealed a significant increase in the signal-to-noise ratio as compared to the polymer alone. Preliminary results have shown a successful increase in polymer's echogenic properties, without undermining its mechanical and cytocompatibility properties.

Focused Ultrasound Biofilm Ablation: Investigation of Histotripsy for the Treatment of Catheter-Associated Urinary Tract Infections (CAUTIs).

Urinary catheters often become contaminated with biofilms, resulting in catheter-associated urinary tract infections (CAUTIs) that adversely affect patient outcomes. Histotripsy is a noninvasive focused ultrasound therapy previously developed for the noninvasive ablation of cancerous tumors and soft tissues. Histotripsy has also previously shown the ability to treat biofilms on glass slides and surgical meshes. Here, we investigate the potential of histotripsy for the treatment of CAUTIs for the first time in vitro. Clinically relevant catheter materials (Tygon, Silicone, and latex catheter mimics) and commonly used clinical catheters were tested to determine the feasibility of producing luminal histotripsy bubble clouds. A Pseudomonas aeruginosa (strain PA14) biofilm model was developed and tested to produce luminal biofilms in an in vitro Tygon catheter mimic. This model was treated with histotripsy to determine the ability to remove a luminal biofilm. Finally, the bactericidal effects of histotripsy were tested by treating PA14 suspended inside the Tygon catheter mimic. Results showed that histotripsy produced precise luminal cavitation within all tested catheter mimics and clinical catheters. Histotripsy treatment of a PA14 biofilm with histotripsy reduced luminal biofilm OD590 signal down to background levels. Further, the treatment of suspended PA14 in Luria-Bertani (LB) showed a 3.45 ± 0.11 log10 reduction in CFU/mL after six histotripsy scans across the catheter mimics. Overall, the results of this study demonstrate the potential of histotripsy to provide a new modality for removing bacterial biofilms from catheter-based medical devices and suggest that additional work is warranted to investigate histotripsy for the treatment of CAUTIs and other biomaterial-associated infections.

Bioactive Cellulose Nanocrystal-Poly(ε-Caprolactone) Nanocomposites for Bone Tissue Engineering Applications.

3D-printed bone scaffolds hold great promise for the individualized treatment of critical-size bone defects. Among the resorbable polymers available for use as 3D-printable scaffold materials, poly(ε-caprolactone) (PCL) has many benefits. However, its relatively low stiffness and lack of bioactivity limit its use in load-bearing bone scaffolds. This study tests the hypothesis that surface-oxidized cellulose nanocrystals (SO-CNCs), decorated with carboxyl groups, can act as multi-functional scaffold additives that (1) improve the mechanical properties of PCL and (2) induce biomineral formation upon PCL resorption. To this end, an in vitro biomineralization study was performed to assess the ability of SO-CNCs to induce the formation of calcium phosphate minerals. In addition, PCL nanocomposites containing different amounts of SO-CNCs (1, 2, 3, 5, and 10 wt%) were prepared using melt compounding extrusion and characterized in terms of Young's modulus, ultimate tensile strength, crystallinity, thermal transitions, and water contact angle. Neither sulfuric acid-hydrolyzed CNCs (SH-CNCs) nor SO-CNCs were toxic to MC3T3 preosteoblasts during a 24 h exposure at concentrations ranging from 0.25 to 3.0 mg/mL. SO-CNCs were more effective at inducing mineral formation than SH-CNCs in simulated body fluid (1x). An SO-CNC content of 10 wt% in the PCL matrix caused a more than 2-fold increase in Young's modulus (stiffness) and a more than 60% increase in ultimate tensile strength. The matrix glass transition and melting temperatures were not affected by the SO-CNCs but the crystallization temperature increased by about 5.5°C upon addition of 10 wt% SO-CNCs, the matrix crystallinity decreased from about 43 to about 40%, and the water contact angle decreased from 87 to 82.6°. The abilities of SO-CNCs to induce calcium phosphate mineral formation and increase the Young's modulus of PCL render them attractive for applications as multi-functional nanoscale additives in PCL-based bone scaffolds.

The correlation between gelatin macroscale differences and nanoparticle properties: providing insight into biopolymer variability.

From therapeutic delivery to sustainable packaging, manipulation of biopolymers into nanostructures imparts biocompatibility to numerous materials with minimal environmental pollution during processing. While biopolymers are appealing natural based materials, the lack of nanoparticle (NP) physicochemical consistency has decreased their nanoscale translation into actual products. Insights regarding the macroscale and nanoscale property variation of gelatin, one of the most common biopolymers already utilized in its bulk form, are presented. Novel correlations between macroscale and nanoscale properties were made by characterizing similar gelatin rigidities obtained from different manufacturers. Samples with significant differences in clarity, indicating sample purity, obtained the largest deviations in NP diameter. Furthermore, a statistically significant positive correlation between macroscale molecular weight dispersity and NP diameter was determined. New theoretical calculations proposing the limited number of gelatin chains that can aggregate and subsequently get crosslinked for NP formation were presented as one possible reason to substantiate the correlation analysis. NP charge and crosslinking extent were also related to diameter. Lower gelatin sample molecular weight dispersities produced statistically smaller average diameters (<75 nm), and higher average electrostatic charges (∼30 mV) and crosslinking extents (∼95%), which were independent of gelatin rigidity, conclusions not shown in the literature. This study demonstrates that the molecular weight composition of the starting material is one significant factor affecting gelatin nanoscale properties and must be characterized prior to NP preparation. Identifying gelatin macroscale and nanoscale correlations offers a route toward greater physicochemical property control and reproducibility of new NP formulations for translation to industry.

A review on fabricating tissue scaffolds using vat photopolymerization.

Vat Photopolymerization (stereolithography, SLA), an Additive Manufacturing (AM) or 3D printing technology, holds particular promise for the fabrication of tissue scaffolds for use in regenerative medicine. Unlike traditional tissue scaffold fabrication techniques, SLA is capable of fabricating designed scaffolds through the selective photopolymerization of a photopolymer resin on the micron scale. SLA offers unprecedented control over scaffold porosity and permeability, as well as pore size, shape, and interconnectivity. Perhaps even more significantly, SLA can be used to fabricate vascular networks that may encourage angio and vasculogenesis. Fulfilling this potential requires the development of new photopolymers, the incorporation of biochemical factors into printed scaffolds, and an understanding of the effects scaffold geometry have on cell viability, proliferation, and differentiation. This review compares SLA to other scaffold fabrication techniques, highlights significant advances in the field, and offers a perspective on the field's challenges and future directions. STATEMENT OF SIGNIFICANCE: Engineering de novo tissues continues to be challenging due, in part, to our inability to fabricate complex tissue scaffolds that can support cell proliferation and encourage the formation of developed tissue. The goal of this review is to first introduce the reader to traditional and Additive Manufacturing scaffold fabrication techniques. The bulk of this review will then focus on apprising the reader of current research and provide a perspective on the promising use of vat photopolymerization (stereolithography, SLA) for the fabrication of complex tissue scaffolds.

Poly(ether ester) Ionomers as Water-Soluble Polymers for Material Extrusion Additive Manufacturing Processes.

Water-soluble polymers as sacrificial supports for additive manufacturing (AM) facilitate complex features in printed objects. Few water-soluble polymers beyond poly(vinyl alcohol) enable material extrusion AM. In this work, charged poly(ether ester)s with tailored rheological and mechanical properties serve as novel materials for extrusion-based AM at low temperatures. Melt transesterification of poly(ethylene glycol) (PEG, 8k) and dimethyl 5-sulfoisophthalate afforded poly(ether ester)s of sufficient molecular weight to impart mechanical integrity. Quantitative ion exchange provided a library of poly(ether ester)s with varying counterions, including both monovalent and divalent cations. Dynamic mechanical and tensile analysis revealed an insignificant difference in mechanical properties for these polymers below the melting temperature, suggesting an insignificant change in final part properties. Rheological analysis, however, revealed the advantageous effect of divalent countercations (Ca2+, Mg2+, and Zn2+) in the melt state and exhibited an increase in viscosity of two orders of magnitude. Furthermore, time-temperature superposition identified an elevation in modulus, melt viscosity, and flow activation energy, suggesting intramolecular interactions between polymer chains and a higher apparent molecular weight. In particular, extrusion of poly(PEG8k-co-CaSIP) revealed vast opportunities for extrusion AM of well-defined parts. The unique melt rheological properties highlighted these poly(ether ester) ionomers as ideal candidates for low-temperature material extrusion additive manufacturing of water-soluble parts.

Influence of therapeutic radiation on polycaprolactone and polyurethane biomaterials.

Biomedical polymers are exposed in vivo to ionizing radiation as implants, coatings and bystander materials. High levels of ionizing radiation (e.g. X-ray and gamma) have been reported to cause degradation and/or cross-linking in many polymers. This pilot study sought to determine causes of failure, by investigating how therapeutic radiation affects two different porous polymeric scaffolds: polycaprolactone (PCL) and polyurethane (PU). PCL is a bioresorbable material used in biomedical devices (e.g., dentistry, internal fixation devices and targeted drug delivery capsules). PU is commonly used in medical applications (e.g., coatings for pacemakers, tissue expanders, catheter tubing and wound dressings). PU was specifically fabricated to be a non-degradable polymer in this study. Porous scaffolds, fabricated using solvent casting and/or salt leeching techniques, were placed in phosphate buffered saline (PBS, pH=7.4) and exposed to typical cancer radiotherapy. A total dose of 50 Gy was broken into 25 doses over an eleven-week period. Collected PBS was tested for polymer leachants and degradation products using Gas Chromatography Mass Spectroscopy (GC-MS), results revealed no analyzable leachants from either polymer. Scaffolds were characterized using Environmental Scanning Electron Microscopy, Size-exclusion chromatography (SEC), Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR). No gross visual changes were observed in either polymer, however PU exhibited microstructure changes after irradiation. Increased number average molecular weight and weight average molecular weight in PCL and PU were observed after irradiation, indicating crosslinking. PU displayed an increase in intrinsic viscosity that further confirms increased crosslinking. PCL and PU showed decreases in crystallinity after irradiation, and PU crystallinity shifted from long-range-order hard segments to short-range-order hard segments after irradiation. Results from both PCL and PU suggest changes in polymer backbones. This preliminary study suggests that therapeutic radiation doses cause both degradation and crosslinking in PCL and PU.

Fabrication and characterization of medical grade polyurethane composite catheters for near-infrared imaging.

Peripherally inserted central catheters (PICCs) are hollow polymeric tubes that transport nutrients, blood and medications to neonates. To determine proper PICC placement, frequent X-ray imaging of neonates is performed. Because X-rays pose severe health risks to neonates, safer alternatives are needed. We hypothesize that near infrared (NIR) polymer composites can be fabricated into catheters by incorporating a fluorescent dye (IRDye 800CW) and visualized using NIR imaging. To fabricate catheters, polymer and dye are dry mixed and pressed, sectioned, and extruded to produce hollow tubes. We analyzed surface roughness, stiffness, dye retention, NIR contrast intensity, and biocompatibility. The extrusion process did not significantly alter the mechanical properties of the polymer composites. Over a period of 23 days, only 6.35 ± 5.08% dye leached out of catheters. The addition of 0.025 wt% dye resulted in a 14-fold contrast enhancement producing clear PICC images at 1 cm under a tissue equivalent. The addition of IRDye 800CW did not alter the biocompatibility of the polymer and did not increase adhesion of cells to the surface. We successfully demonstrated that catheters can be imaged without the use of harmful radiation and still maintain the same properties as the unaltered medical grade equivalent.

Electrospun meshes possessing region-wise differences in fiber orientation, diameter, chemistry and mechanical properties for engineering bone-ligament-bone tissues.

Although bone-patellar tendon-bone (B-PT-B) autografts are the gold standard for repair of anterior cruciate ligament ruptures, they suffer from drawbacks such as donor site morbidity and limited supply. Engineered tissues modeled after B-PT-B autografts are promising alternatives because they have the potential to regenerate connective tissue and facilitate osseointegration. Towards the long-term goal of regenerating ligaments and their bony insertions, the objective of this study was to construct 2D meshes and 3D cylindrical composite scaffolds - possessing simultaneous region-wise differences in fiber orientation, diameter, chemistry and mechanical properties - by electrospinning two different polymers from off-set spinnerets. Using a dual drum collector, 2D meshes consisting of an aligned polycaprolactone (PCL) fiber region, randomly oriented poly(lactide-co-glycolide) (PLGA) fiber region and a transition region (comprised of both PCL and PLGA fibers) were prepared, and region-wise differences were confirmed by microscopy and tensile testing. Bone marrow stromal cells (BMSCs) cultured on these meshes exhibited random orientations and low aspect ratios on the random PLGA regions, and high aspect ratios and alignment on the aligned PCL regions. Next, meshes containing an aligned PCL region flanked by two transition regions and two randomly oriented PLGA regions were prepared and processed into 3D cylindrical composite scaffolds using an interpenetrating photo-crosslinkable polyethylene glycol diacrylate hydrogel to recapitulate the shape of B-PT-B autografts. Tensile testing indicated that cylindrical composites were mechanically robust, and eventually failed due to stress concentration in the aligned PCL region. In summary, this study demonstrates a process to fabricate electrospun meshes possessing region-wise differences in properties that can elicit region-dependent cell responses, and be readily processed into scaffolds with the shape of B-PT-B autografts.

In vivo skeletal muscle biocompatibility of composite, coaxial electrospun, and microfibrous scaffolds.

One weakness with currently researched skeletal muscle tissue replacement is the lack of contraction and relaxation during the regenerative process. A biocompatible scaffold that can act similar to the muscle would be a pivotal innovation. Coaxial electrospun scaffolds, capable of movement with electrical stimulation, were created using poly(ɛ-caprolactone) (PCL), multiwalled carbon nanotubes (MWCNT), and a (83/17 or 40/60) poly(acrylic acid)/poly(vinyl alcohol) (PAA/PVA) hydrogel. The two scaffolds were implanted into Sprague-Dawley rat vastus lateralis muscle and compared with a phosphate-buffered saline injection sham surgery and an unoperated control. No complications or adverse effects were observed. Rats were sacrificed on days 7, 14, 21, and 28 postimplantation and biocompatibility assessed using enzymatic activity, fibrosis formation, inflammation, scaffold cellular infiltration, and neovascularization. Serum creatine kinase and lactate dehydrogenase levels were significantly higher in scaffold-implanted rats compared with the control on day 7, but returned to baseline by day 14. Day 7 scaffolds showed significant inflammation and fibrosis that decreased over time. Fibroblasts infiltrated the scaffolds early, but decreased with time, while myogenic cell numbers increased. Neovascularization of both scaffolds occurred as early as day 7. We conclude that the PCL-MWCNT-PAA/PVA scaffolds are biocompatible and suitable for muscle regeneration as myogenic cell growth was supported.

Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behavior.

Calcium phosphate ceramics (CPCs) have been widely used as biomaterials for the regeneration of bone tissue because of their ability to induce osteoblastic differentiation in progenitor cells. Despite the progress made towards fabricating CPCs possessing a range of surface features and chemistries, the influence of material properties in orchestrating cellular events such as adhesion and differentiation is still poorly understood. Specifically, questions such as why certain CPCs may be more osteoinductive than others, and how material properties contribute to osteoinductivity/osteoconductivity remain unanswered. Therefore, this review article systematically discusses the effects of the physical (e.g. surface roughness) and chemical properties (e.g. solubility) of CPCs on protein adsorption, cell adhesion and osteoblastic differentiation in vitro. The review also provides a summary of possible signaling pathways involved in osteoblastic differentiation in the presence of CPCs. In summary, these insights on the contribution of material properties towards osteoinductivity and the role of signaling molecules involved in osteoblastic differentiation can potentially aid the design of CPC-based biomaterials that support bone regeneration without the need for additional biochemical supplements.

Response of bone marrow stromal cells to graded co-electrospun scaffolds and its implications for engineering the ligament-bone interface.

Biomaterial scaffolds with gradients in architecture, mechanical and chemical properties have the potential to improve the osseointegration of ligament grafts by recapitulating phenotypic gradients that exist at the natural ligament-bone (L-B) interface. Towards the larger goal of regenerating the L-B interface, this in vitro study was performed to investigate the potential of two scaffolds with mineral gradients in promoting a spatial gradient of osteoblastic differentiation. Specifically, the first graded scaffold was fabricated by co-electrospinning two polymer solutions (one doped with nano-hydroxyapatite particles) from offset spinnerets, while the second was created by immersing the first scaffold in a 5 × simulated body fluid. Rat bone marrow stromal cells, cultured in the presence of osteogenic supplements, were found to be metabolically active on all regions of both scaffolds after 1 and 7 days of culture. Gene expression of bone morphogenic protein-2 and osteopontin was elevated on mineral-containing regions as compared to regions without mineral, while the expression of alkaline phosphatase mRNA revealed the opposite trend. Finally, the presence of osteopontin and bone sialoprotein confirmed osteoblastic phenotypic maturation by day 28. This study indicates that co-electrospun scaffolds with gradients in mineral content can guide the formation of phenotypic gradients and may thus promote the regeneration of the L-B interface.

Fabrication of a model continuously graded co-electrospun mesh for regeneration of the ligament-bone interface.

Current scaffolds for the regeneration of anterior cruciate ligament injuries are unable to capture intricate mechanical and chemical gradients present in the natural ligament-bone interface. As a result, stress concentrations can develop at the scaffold-bone interface, leading to poor osseointegration. Hence, scaffolds that possess appropriate mechano-chemical gradients would help establish normal loading properties at the interface, while promoting scaffold integration with bone. With the long-term goal of investigating regeneration of the ligament-bone interface, this feasibility study aimed to fabricate a continuously graded mesh. Specifically, graded meshes were fabricated by co-electrospinning nanohydroxyapatite/polycaprolactone (nHAP-PCL) and poly(ester urethane) urea elastomer solutions from offset spinnerets. Next, mineral crystallites were selectively deposited on the nHAP-PCL fibers by treatment with a 5× simulated body fluid (5× SBF). X-ray diffraction and energy-dispersive spectroscopy indicated calcium-deficient hydroxyapatite-like mineral crystallites with an average Ca/P ratio of 1.48. Tensile testing demonstrated the presence of a mechanical gradient, which became more pronounced upon treatment with 5× SBF. Finally, biocompatibility of the graded meshes was verified using an MC3T3-E1 osteoprogenitor cell line. The study demonstrates that graded meshes, for potential application in interfacial tissue engineering, can be fabricated by co-electrospinning.