Deformation and Durability of Soft Three-Dimensional-Printed Polycarbonate Urethane Porous Membranes for Potential Use in Pelvic Organ Prolapse.

Pelvic organ prolapse (POP) is the herniation of the pelvic organs into the vaginal space, resulting in the feeling of a bulge and organ dysfunction. Treatment of POP often involves repositioning the organs using a polypropylene mesh, which has recently been found to have relatively high rates of complications. Complications have been shown to be related to stiffness mismatches between the vagina and polypropylene, and unstable knit patterns resulting in mesh deformations with mechanical loading. To overcome these limitations, we have three-dimensional (3D)-printed a porous, monofilament membrane composed of relatively soft polycarbonate-urethane (PCU) with a stable geometry. PCU was chosen for its tunable properties as it is comprised of both hard and soft segments. The bulk mechanical properties of PCU were first characterized by testing dogbone samples, demonstrating the dependence of PCU mechanical properties on its measurement environment and the effect of print pathing. The pore dimensions and load-relative elongation response of the 3D-printed PCU membranes under monotonic tensile loading were then characterized. Finally, a fatigue study was performed on the 3D-printed membrane to evaluate durability, showing a similar fatigue resistance with a commercial synthetic mesh and hence its potential as a replacement.

Outcomes of Surgical Reconstruction Using Custom 3D-Printed Porous Titanium Implants for Critical-Sized Bone Defects of the Foot and Ankle.

BACKGROUND: Treating critically sized defects (CSDs) of bone remains a significant challenge in foot and ankle surgery. Custom 3D-printed implants are being offered to a small but growing subset of patients as a salvage procedure in lieu of traditional alternates such as structural allografts after the patient has failed prior procedures. The long-term outcomes of 3D-printed implants are still unknown and understudied because of the limited number of cases and short follow-up durations. The purpose of this study was to evaluate the outcomes of patients who received custom 3D-printed implants to treat CSDs of the foot and ankle in an attempt to aid surgeons in selecting appropriate surgical candidates. METHODS: This was a retrospective study to assess surgical outcomes of patients who underwent implantation of a custom 3D-printed implant made with medical-grade titanium alloy powder (Ti-6Al-4V) to treat CSDs of the foot and ankle between June 1, 2014, and September 30, 2019. All patients had failed previous nonoperative or operative management before proceeding with treatment with a custom 3D-printed implant. Univariate and multivariate odds ratios (ORs) of a secondary surgery and implant removal were calculated for perioperative variables. RESULTS: There were 39 cases of patients who received a custom 3D-printed implant with at least 1 year of follow-up. The mean follow-up time was 27.0 (12-74) months. Thirteen of 39 cases (33.3%) required a secondary surgery and 10 of 39 (25.6%) required removal of the implant because of septic nonunion (6/10) or aseptic nonunion (4/10). The mean time to secondary surgery was 10 months (1-22). Multivariate logistic regression revealed that patients with neuropathy were more likely to require a secondary surgery with an OR of 5.76 (P = .03). CONCLUSION: This study demonstrated that 74% of patients who received a custom 3D-printed implant for CSDs did not require as subsequent surgery (minimum of 1-year follow-up). Neuropathy was significantly associated with the need for a secondary surgery. This is the largest series to date demonstrating the efficacy of 3D-printed custom titanium implants. As the number of cases using patient-specific 3D-printed titanium implant increases, larger cohorts of patients should be studied to identify other high-risk groups and possible interventions to improve surgical outcomes. LEVEL OF EVIDENCE: Level IV, case series.

Computational and image processing methods for analysis and automation of anatomical alignment and joint spacing in reconstructive surgery.

PURPOSE: Reconstructive surgeries to treat a number of musculoskeletal conditions, from arthritis to severe trauma, involve implant placement and reconstructive planning components. Anatomically matched 3D-printed implants are becoming increasingly patient-specific; however, the preoperative planning and design process requires several hours of manual effort from highly trained engineers and clinicians. Our work mitigates this problem by proposing algorithms for the automatic re-alignment of unhealthy anatomies, leading to more efficient, affordable, and scalable treatment solutions. METHODS: Our solution combines global alignment techniques such as iterative closest points with novel joint space refinement algorithms. The latter is achieved by a low-dimensional characterization of the joint space, computed from the distribution of the distance between adjacent points in a joint. RESULTS: Experimental validation is presented on real clinical data from human subjects. Compared with ground truth healthy anatomies, our algorithms can reduce misalignment errors by 22% in translation and 19% in rotation for the full foot-and-ankle and 37% in translation and 39% in rotation for the hindfoot only, achieving a performance comparable to expert technicians. CONCLUSION: Our methods and histogram-based metric allow for automatic and unsupervised alignment of anatomies along with techniques for global alignment of complex arrangements such as the foot-and-ankle system, a major step toward a fully automated and data-driven re-positioning, designing, and diagnosing tool.

Polycarbonate Urethane Mesh: A New Material for Pelvic Reconstruction.

OBJECTIVE: Polycarbonate urethane (PCU) is a new biomaterial, and its mechanical properties can be tailored to match that of vaginal tissue. We aimed to determine whether vaginal host immune and extracellular matrix responses differ after PCU versus lightweight polypropylene (PP) mesh implantation. METHODS: Hysterectomy and ovariectomy were performed on 24 Sprague-Dawley rats. Animals were divided into 3 groups: (1) PCU vaginal mesh, (2) PP vaginal mesh, and (3) sham controls. Vagina-mesh complexes or vaginas (controls) were excised 90 days after surgery. We quantified responses by comparing: (1) histomorphologic scoring of hematoxylin and eosin- and Masson trichrome-stained slides, (2) macrophage subsets (immunolabeling), (3) pro-inflammatory and anti-inflammatory cytokines (Luminex panel), (4) matrix metalloproteinase (MMP)-2 and -9 using an enzyme-linked immunosorbent assay, and (5) type I/III collagen using picrosirius red staining. RESULTS: There was no difference in histomorphologic score between PCU and PP (P = 0.211). Although the histomorphologic response was low surrounding all mesh fibers, groups with PCU and PP mesh had a higher histomorphologic score than the control group (P < 0.005 and P < 0.002, respectively). There were no differences between groups in terms of macrophage subsets, pro-inflammatory cytokines, anti-inflammatory cytokines, MMP-2 and MMP-9, or collagen ratio. CONCLUSIONS: Polycarbonate urethane, an elastomer with material properties similar to those of vaginal tissue, elicits minimal host inflammatory responses in a rat model. Because its implantation does not elicit more inflammation than currently used lightweight PP, using PCU for prolapse mesh warrants further investigation with larger animal models.

Evaluation of Host Immune Cellular and Extracellular Matrix Responses to Prolapse Mesh With and Without Tension in a Rat Model.

OBJECTIVES: We sought to determine whether vaginal host immune cellular and extracellular matrix responses are altered in a rat sacrocolpopexy model when lightweight polypropylene mesh is attached on tension versus without tension. METHODS: We performed hysterectomy and ovariectomy in 32 Sprague-Dawley rats. Animals were assigned to 4 groups (n = 8/group): (1) controls with sham operation only (control), (2) mesh sutured only on the vagina (vaginal mesh), (3) sacrocolpopexy without tension, and (4) sacrocolpopexy with tension. Ninety days later, we excised vagina-mesh complexes. A histomorphologic scoring system of hematoxylin/eosin and Masson trichrome stained slides was used to assess host inflammatory responses. The cellular inflammatory response was further quantified using (1) identification of M1 and M2 macrophage subsets and (2) quantification of proinflammatory and anti-inflammatory cytokines. The extracellular matrix response was evaluated by measuring (1) matrix metalloproteinase-2 and matrix metalloproteinase-9 levels and (2) type I/III collagen. RESULTS: Histomorphological tissue responses were greater in all groups with mesh compared with sham controls. Both sacrocolpopexy groups had similar scores, but each group scored significantly higher than the vaginal mesh group. Among the 4 groups, there were no statistically significant differences in M1 or M2 macrophage subsets, proinflammatory or anti-inflammatory cytokines, or extracellular matrix remodeling responses. CONCLUSIONS: Attachment of prolapse mesh resulted in an increased histologic inflammatory response independent of tension. Other markers of cellular inflammation and extracellular matrix remodeling showed no differences among experimental groups. Tension on lightweight polypropylene mesh did not significantly alter the host response in this rat sacrocolpopexy model.

Modulating antibiotic release from reservoirs in 3D-printed orthopedic devices to treat periprosthetic joint infection.

Periprosthetic joint infection is a costly debilitating affliction following total joint arthroplasty. Despite a relatively low incidence rate, periprosthetic joint infection is an increasing problem due to a substantial increase in arthroplasty surgeries over time. The current treatment is replacing the primary implant with a temporary bone cement spacer that releases antibiotics over time. However, the spacer is mechanically weak with an ineffective antibiotic release. Alternatively, three-dimensional (3D)-printed reservoirs in high-strength devices have the potential to release antibiotics long term in a controlled manner. In this study, 3D-printed reservoirs were loaded with calcium sulfate embedded with gentamicin. In vitro antibiotic release is tuned by varying reservoir parameters, such as channel length, diameter, and quantity. In addition, a straightforward computational model effectively predicts antibiotic release curves to rapidly design devices with a preferred release profile. Overall, this study highlights a novel approach to potentially develop high-strength joint implants with the long-term effective release of antibiotics to treat the periprosthetic joint infection.

Effects of Surface Topography and Chemistry on Polyether-Ether-Ketone (PEEK) and Titanium Osseointegration.

STUDY DESIGN: An in vivo study examining the functional osseointegration of smooth, rough, and porous surface topographies presenting polyether-ether-ketone (PEEK) or titanium surface chemistry. OBJECTIVE: To investigate the effects of surface topography and surface chemistry on implant osseointegration. SUMMARY OF BACKGROUND DATA: Interbody fusion devices have been used for decades to facilitate fusion across the disc space, yet debate continues over their optimal surface topography and chemistry. Though both factors influence osseointegration, the relative effects of each are not fully understood. METHODS: Smooth, rough, and porous implants presenting either a PEEK or titanium surface chemistry were implanted into the proximal tibial metaphyses of 36 skeletally mature male Sprague Dawley rats. At 8 weeks, animals were euthanized and bone-implant interfaces were subjected to micro-computed tomography analysis (n = 12), histology (n = 4), and biomechanical pullout testing (n = 8) to assess functional osseointegration and implant fixation. RESULTS: Micro-computed tomography analysis demonstrated that bone ingrowth was 38.9 ±â€Š2.8% for porous PEEK and 30.7 ±â€Š3.3% for porous titanium (P = 0.07). No differences in fixation strength were detected between porous PEEK and porous titanium despite titanium surfaces exhibiting an overall increase in bone-implant contact compared with PEEK (P < 0.01). Porous surfaces exhibited increased fixation strength compared with smooth and rough surfaces regardless of surface chemistry (P < 0.05). Across all groups both surface topography and chemistry had a significant overall effect on fixation strength (P < 0.05), but topography accounted for 65.3% of the total variance (ω = 0.65), whereas surface chemistry accounted for 5.9% (ω = 0.06). CONCLUSIONS: The effect of surface topography (specifically porosity) dominated the effect of surface chemistry in this study and could lead to further improvements in orthopedic device design. The poor osseointegration of existing smooth PEEK implants may be linked more to their smooth surface topography rather than their material composition. LEVEL OF EVIDENCE: N/A.

Application of a novel suture anchor to abdominal wall closure.

BACKGROUND: Mesh suture used in high-tension wound closures produces large knots susceptible to increased palpability, infection, and foreign body response; yet has superior tensile strength and increased resistance to cutting through tissue compared to standard suture. This study investigates mesh suture fixation in abdominal tissue with a knotless novel, low-profile anchor-clip. METHODS: Single and double end fixation of mesh suture in swine rectus abdominus fascia with an anchor-clip, a knot, and predicate device fixation underwent cyclic testing followed by pull-to-failure testing. RESULTS: Failure load of standard knot, single corkscrew and double anchor-clip were not statistically different, but were significantly greater than single anchor-clip and double corkscrew fixation (p > 0.05). CONCLUSIONS: The anchor-clip is ∼60% smaller than a standard knot while maintaining fixation strength when exposed to physiologic forces using double anchor-clip fixation in abdominal wall closure.

Modifying hernia mesh design to improve device mechanical performance and promote tension-free repair.

PURPOSE: Approximately 348,000 ventral hernia repairs are performed annually in the United States and the incisional hernia recurrence rate is approximately 20% as a result of suture and mesh device failure. Device failure is related to changes at the suture/tissue interface that leads to acute or chronic suture pull-through and surgical failure. To better manage mechanical tension, we propose a modified mesh design with extensions and demonstrate its mechanical superiority. METHODS: Comparative uniaxial static tensile testing was conducted on polypropylene suture and a modified mesh. Subsequently, a standard of care (SOC) mesh and modified mesh were evaluated using a tensometer in an acute hernia bench-top model. RESULTS: Modified mesh breaking strength, extension knot breaking strength, extension disruption, and extension anchoring were superior to suture (p < .05). Modified mesh ultimate tensile strength of anchoring was superior to SOC mesh (p < .05). Various stitch patterns and modifications in device design significantly improved device tension-free performance far beyond clinically relevant benchmarks (p < .05). CONCLUSIONS: Testing demonstrates that the modified mesh outperforms SOC mesh and suture in all tested failure modes. SOC hernia mesh tears through tissue at stress levels below maximum physiologic stress, whereas, the modified hernia mesh is up to 200% stronger than SOC mesh at resisting suture tearing through tissue and maintains anchoring at stresses far beyond clinically relevant benchmarks. Modifying hernia mesh design significantly improves device mechanical performance and enhances tension-free repair.

Impaction durability of porous polyether-ether-ketone (PEEK) and titanium-coated PEEK interbody fusion devices.

BACKGROUND CONTEXT: Various surface modifications, often incorporating roughened or porous surfaces, have recently been introduced to enhance osseointegration of interbody fusion devices. However, these topographical features can be vulnerable to damage during clinical impaction. Despite the potential negative impact of surface damage on clinical outcomes, current testing standards do not replicate clinically relevant impaction loading conditions. PURPOSE: The purpose of this study was to compare the impaction durability of conventional smooth polyether-ether-ketone (PEEK) cervical interbody fusion devices with two surface-modified PEEK devices that feature either a porous structure or plasma-sprayed titanium coating. STUDY DESIGN/SETTING: A recently developed biomechanical test method was adapted to simulate clinically relevant impaction loading conditions during cervical interbody fusion procedures. METHODS: Three cervical interbody fusion devices were used in this study: smooth PEEK, plasma-sprayed titanium-coated PEEK, and porous PEEK (n=6). Following Kienle et al., devices were impacted between two polyurethane blocks mimicking vertebral bodies under a constant 200 N preload. The posterior tip of the device was placed at the entrance between the polyurethane blocks, and a guided 1-lb weight was impacted upon the anterior face with a maximum speed of 2.6 m/s to represent the strike force of a surgical mallet. Impacts were repeated until the device was fully impacted. Porous PEEK durability was assessed using micro-computed tomography (µCT) pre- and postimpaction. Titanium-coating coverage pre- and postimpaction was assessed using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy. Changes to the surface roughness of smooth and titanium-coated devices were also evaluated. RESULTS: Porous PEEK and smooth PEEK devices showed minimal macroscopic signs of surface damage, whereas the titanium-coated devices exhibited substantial visible coating loss. Quantification of the porous PEEK deformation demonstrated that the porous structure maintained a high porosity (>65%) following impaction that would be available for bone ingrowth, and exhibited minimal changes to pore size and depth. SEM and energy dispersive X-ray spectroscopy analysis of titanium-coated devices demonstrated substantial titanium coating loss after impaction that was corroborated with a decrease in surface roughness. Smooth PEEK showed minimal signs of damage using SEM, but demonstrated a decrease in surface roughness. CONCLUSION: Although recent surface modifications to interbody fusion devices are beneficial for osseointegration, they may be susceptible to damage and wear during impaction. The current study found porous PEEK devices to show minimal damage during simulated cervical impaction, whereas titanium-coated PEEK devices lost substantial titanium coverage.

Substrate Stiffness Controls Osteoblastic and Chondrocytic Differentiation of Mesenchymal Stem Cells without Exogenous Stimuli.

Stem cell fate has been linked to the mechanical properties of their underlying substrate, affecting mechanoreceptors and ultimately leading to downstream biological response. Studies have used polymers to mimic the stiffness of extracellular matrix as well as of individual tissues and shown mesenchymal stem cells (MSCs) could be directed along specific lineages. In this study, we examined the role of stiffness in MSC differentiation to two closely related cell phenotypes: osteoblast and chondrocyte. We prepared four methyl acrylate/methyl methacrylate (MA/MMA) polymer surfaces with elastic moduli ranging from 0.1 MPa to 310 MPa by altering monomer concentration. MSCs were cultured in media without exogenous growth factors and their biological responses were compared to committed chondrocytes and osteoblasts. Both chondrogenic and osteogenic markers were elevated when MSCs were grown on substrates with stiffness <10 MPa. Like chondrocytes, MSCs on lower stiffness substrates showed elevated expression of ACAN, SOX9, and COL2 and proteoglycan content; COMP was elevated in MSCs but reduced in chondrocytes. Substrate stiffness altered levels of RUNX2 mRNA, alkaline phosphatase specific activity, osteocalcin, and osteoprotegerin in osteoblasts, decreasing levels on the least stiff substrate. Expression of integrin subunits α1, α2, α5, αv, ß1, and ß3 changed in a stiffness- and cell type-dependent manner. Silencing of integrin subunit beta 1 (ITGB1) in MSCs abolished both osteoblastic and chondrogenic differentiation in response to substrate stiffness. Our results suggest that substrate stiffness is an important mediator of osteoblastic and chondrogenic differentiation, and integrin ß1 plays a pivotal role in this process.

Local deformation behavior of surface porous polyether-ether-ketone.

Surface porous polyether-ether-ketone has the ability to maintain the tensile monotonic and cyclic strength necessary for many load bearing orthopedic applications while providing a surface that facilitates bone ingrowth; however, the relevant deformation behavior of the pore architecture in response to various loading conditions is not yet fully characterized or understood. The focus of this study was to examine the compressive and wear behavior of the surface porous architecture using micro Computed Tomography (micro CT). Pore architectures of various depths (~0.5-2.5mm) and pore sizes (212-508µm) were manufactured using a melt extrusion and porogen leaching process. Compression testing revealed that the pore architecture deforms in the typical three staged linear elastic, plastic, and densification stages characteristic of porous materials. The experimental moduli and yield strengths decreased as the porosity increased but there was no difference in properties between pore sizes. The porous architecture maintained a high degree of porosity available for bone-ingrowth at all strains. Surface porous samples showed no increase in wear rate compared to injection molded samples, with slight pore densification accompanying wear.

Change in surface roughness by dynamic shape-memory acrylate networks enhances osteoblast differentiation.

Microscale surface roughness has been shown to enhance osseointegration of titanium implants through increased osteoblast differentiation while osteoblast proliferation remains greater on smooth titanium. Taking advantage of these phenomena, we developed a shape memory (meth)acrylate copolymer with thermomechanical properties that created a time-dependent dynamic surface change from smooth to rough under in vitro cell culture conditions and evaluated the effect of the shape recovery on osteoblast response. Rough topographies were created using soft lithography techniques to mimic those found on clinically-used Ti surfaces (machined smooth; acid-etched; grit-blasted). The surface roughness was then reduced to smooth via compression and shown to fully recover within 24 h in culture conditions. When grown under static conditions, osteoblast number, alkaline phosphatase specific activity (ALP), and osteoprotegerin (OPG) and vascular endothelial growth factor (VEGF) production were unaffected by polymer surface roughness, but osteocalcin (OCN) was increased on the grit-blasted polymer mimic. Under dynamic conditions, DNA was reduced but OCN and OPG were increased on the compressed grit-blasted polymer at 3 days compared to static surfaces. The present study indicates that responses to polymer surface are sensitive to time-dependent changes in topography. The use of a shape memory polymer with dynamic surface roughness may improve osseointegration.

Do Surface Porosity and Pore Size Influence Mechanical Properties and Cellular Response to PEEK?

BACKGROUND: Despite its widespread use in orthopaedic implants such as soft tissue fasteners and spinal intervertebral implants, polyetheretherketone (PEEK) often suffers from poor osseointegration. Introducing porosity can overcome this limitation by encouraging bone ingrowth; however, the corresponding decrease in implant strength can potentially reduce the implant's ability to bear physiologic loads. We have previously shown, using a single pore size, that limiting porosity to the surface of PEEK implants preserves strength while supporting in vivo osseointegration. However, additional work is needed to investigate the effect of pore size on both the mechanical properties and cellular response to PEEK. QUESTIONS/PURPOSES: (1) Can surface porous PEEK (PEEK-SP) microstructure be reliably controlled? (2) What is the effect of pore size on the mechanical properties of PEEK-SP? (3) Do surface porosity and pore size influence the cellular response to PEEK? METHODS: PEEK-SP was created by extruding PEEK through NaCl crystals of three controlled ranges: 200 to 312, 312 to 425, and 425 to 508 µm. Micro-CT was used to characterize the microstructure of PEEK-SP. Tensile, fatigue, and interfacial shear tests were performed to compare the mechanical properties of PEEK-SP with injection-molded PEEK (PEEK-IM). The cellular response to PEEK-SP, assessed by proliferation, alkaline phosphatase activity, vascular endothelial growth factor production, and calcium content of osteoblast, mesenchymal stem cell, and preosteoblast (MC3T3-E1) cultures, was compared with that of machined smooth PEEK and Ti6Al4V. RESULTS: Micro-CT analysis showed that PEEK-SP layers possessed pores that were 284 ± 35 µm, 341 ± 49 µm, and 416 ± 54 µm for each pore size group. Porosity and pore layer depth ranged from 61% to 69% and 303 to 391 µm, respectively. Mechanical testing revealed tensile strengths > 67 MPa and interfacial shear strengths > 20 MPa for all three pore size groups. All PEEK-SP groups exhibited > 50% decrease in ductility compared with PEEK-IM and demonstrated fatigue strength > 38 MPa at one million cycles. All PEEK-SP groups also supported greater proliferation and cell-mediated mineralization compared with smooth PEEK and Ti6Al4V. CONCLUSIONS: The PEEK-SP formulations evaluated in this study maintained favorable mechanical properties that merit further investigation into their use in load-bearing orthopaedic applications and supported greater in vitro osteogenic differentiation compared with smooth PEEK and Ti6Al4V. These results are independent of pore sizes ranging 200 µm to 508 µm. CLINICAL RELEVANCE: PEEK-SP may provide enhanced osseointegration compared with current implants while maintaining the structural integrity to be considered for several load-bearing orthopaedic applications such as spinal fusion or soft tissue repair.

High-strength, surface-porous polyether-ether-ketone for load-bearing orthopedic implants.

Despite its widespread clinical use in load-bearing orthopedic implants, polyether-ether-ketone (PEEK) is often associated with poor osseointegration. In this study, a surface-porous PEEK material (PEEK-SP) was created using a melt extrusion technique. The porous layer was 399.6±63.3 µm thick and possessed a mean pore size of 279.9±31.6 µm, strut spacing of 186.8±55.5 µm, porosity of 67.3±3.1% and interconnectivity of 99.9±0.1%. Monotonic tensile tests showed that PEEK-SP preserved 73.9% of the strength (71.06±2.17 MPa) and 73.4% of the elastic modulus (2.45±0.31 GPa) of as-received, injection-molded PEEK. PEEK-SP further demonstrated a fatigue strength of 60.0 MPa at one million cycles, preserving 73.4% of the fatigue resistance of injection-molded PEEK. Interfacial shear testing showed the pore layer shear strength to be 23.96±2.26 MPa. An osseointegration model in the rat revealed substantial bone formation within the pore layer at 6 and 12 weeks via microcomputed tomography and histological evaluation. Ingrown bone was more closely apposed to the pore wall and fibrous tissue growth was reduced in PEEK-SP when compared to non-porous PEEK controls. These results indicate that PEEK-SP could provide improved osseointegration while maintaining the structural integrity necessary for load-bearing orthopedic applications.

Effect of poly(ethylene glycol) diacrylate concentration on network properties and in vivo response of poly(ß-amino ester) networks.

Poly(ß-amino ester) networks have shown promise as tissue scaffolds. The objective of this work was to examine the effect of changing poly(ethylene glycol) diacrylate concentration on poly(ß-amino ester) network properties and to assess the degradable polymers' in vivo response, using magnetic resonance imaging (MRI) and immunohistochemistry. The networks were synthesized from hexanediol diacrylate (HDDA), poly(ethylene glycol) diacrylate (PEGDA), and a primary amine, 3-methoxypropylamine (3-MOPA), with a fixed overall molar ratio of diacrylate to amine. Network properties were verified to insure that the networks possessed equivalent initial properties and structure other than chemistry. The effect of varying PEGDA concentration on water content, mass loss, and modulus was determined, where increasing the concentration of PEGDA increases both water content, mass loss rate, and decreases modulus. We also show that manipulating the network composition at ratios of 0:100, 10:90 and 25:75 (PEGDA:HDDA) does not elicit a major inflammatory response to subcutaneous implantation of the networks in mice. This work provides a foundation for tailoring poly(ß-amino ester) networks, based on degradation rate and modulus, as a means to tune the polymer properties for various biomedical applications.

Synthesis, characterization, and cyclic stress-influenced degradation of a poly(ethylene glycol)-based poly(beta-amino ester).

This study aims to fundamentally understand the polymer network formed by poly(ethylene glycol) diacrylate (PEGDA) MW 700 and 3-methoxypropylamine (3MOPA) as well as to characterize the degradation response of this material with and without applied cyclic stress. Macromer reaction chemistry was confirmed by (1)H NMR measurements. UV calorimetry analysis revealed conditions of network formation were dependent on molecular weight of the PEGDA monomer and light intensity. The glass transition temperature of all networks PEGDA MW 258, 575, and 700 were measured and found to be in the range of -40 to -30 degrees C with a rubbery moduli ranging from 4 to 10 MPa by DMA. Degradation studies were performed with and without applied cyclical stress, and in most cases, elastic modulus decrease and mass loss occurred steadily over a 24-h period. Unexpected partial crystallization was discovered to occur in the networks containing higher molecular weight PEGDA in the presence of humidity and high frequency cyclic loading. In all materials, high frequency applied cyclic loading during in situ degradation resulted in catastrophic fracture of the material prior to an appreciable decrease in modulus.

Unconstrained recovery characterization of shape-memory polymer networks for cardiovascular applications.

Shape-memory materials have been proposed in biomedical device design due to their ability to facilitate minimally invasive surgery and recover to a predetermined shape in vivo. Use of the shape-memory effect in polymers is proposed for cardiovascular stent interventions to reduce the catheter size for delivery and offer highly controlled and tailored deployment at body temperature. Shape-memory polymer networks were synthesized via photopolymerization of tert-butyl acrylate and poly(ethylene glycol) dimethacrylate to provide precise control over the thermomechanical response of the system. The free recovery response of the polymer stents at body temperature was studied as a function of glass transition temperature (T(g)), crosslink density, geometrical perforation, and deformation temperature, all of which can be independently controlled. Room temperature storage of the stents was shown to be highly dependent on T(g) and crosslink density. The pressurized response of the stents is also demonstrated to depend on crosslink density. This polymer system exhibits a wide range of shape-memory and thermomechanical responses to adapt and meet specific needs of minimally invasive cardiovascular devices.

Daily variability of Listeria contamination patterns in a cold-smoked salmon processing operation.

An understanding of Listeria transmission and contamination patterns in processing environments of ready-to-eat foods is critical for improving control of Listeria monocytogenes. A cold-smoked fish processing operation was the site used to study variability in Listeria contamination in a processing environment associated with a ready-to-eat food product throughout one production week (five consecutive days). Intensive testing was conducted on finished products and environmental samples collected at the beginning, middle, and end of each working day. A total of 20 finished products and 22 to 36 environmental samples were collected at each sampling time, and an additional 12 environmental samples were collected on days 4 and 5. Overall, a total of 782 samples, 300 finished products and 482 environmental samples, were tested. All samples were collected from processing steps after smoking, including skinning, trimming, slicing, staging, and packing. A total of 28 finished and 57 environmental samples (9.3 and 11.8%, respectively) were positive for Listeria spp. (including 1 and 5 samples positive for L. monocytogenes, respectively). DNA sequencing of the sigB gene allowed differentiation of eight Listeria subtypes. Listeria prevalence varied significantly between days, and a high prevalence in both environmental samples and finished products on day 3 was likely associated with a point source contamination event by a single Listeria welshimeri subtype. There were no consistent differences in Listeria prevalence among samples collected from the beginning, middle, and end of the production day, but subtype data often revealed unique contamination patterns for samples collected at different times of a given day. Listeria contamination patterns and prevalences were highly variable between days and within a given day. These findings indicate that chance events play an important role in the contamination of finished products, thus complicating efforts to define Listeria transmission patterns in processing environments associated with ready-to-eat foods.