A novel biocompatible polymeric blend for applications requiring high toughness and tailored degradation rate.

Finding the right balance in mechanical properties and degradation rate of biodegradable materials for biomedical applications is challenging, not only at the time of implantation but also during biodegradation. For instance, high elongation at break and toughness with a mid-term degradation rate are required for tendon scaffold or suture application, which cannot be found in each alpha polyester individually. Here, we hypothesise that blending semi-crystalline poly(p-dioxanone) (PDO) and poly(lactide-co-caprolactone) (LCL) in a specific composition will enhance the toughness while also enabling tailored degradation times. Hence, blends of PDO and LCL (PDO/LCL) were prepared in varying concentrations and formed into films by solvent casting. We thoroughly characterised the chemical, thermal, morphological, and mechanical properties of the new blends before and during hydrolytic degradation. Cellular performance was determined by seeding mouse fibroblasts onto the samples and culturing for 72 hours, before using proliferation assays and confocal imaging. We found that an increase in LCL content causes a decrease in hydrolytic degradation rate, as indicated by induced crystallinity, surface and bulk erosions, and tensile properties. Interestingly, the noncytotoxic blend containing 30% PDO and 70% LCL (PDO3LCL7) resulted in small PDO droplets uniformly dispersed within the LCL matrix and demonstrated a tailored degradation rate and toughening behaviour with a notable strain-hardening effect reaching 320% elongation at break; over 3 times the elongation of neat LCL. In summary, this work highlights the potential of PDO3LCL7 as a biomaterial for biomedical applications like tendon tissue engineering or high-performance absorbable sutures.

An experimental and numerical comparison of the rupture locations of an abdominal aortic aneurysm.

PURPOSE: To identify the rupture locations of idealized physical models of abdominal aortic aneurysm (AAA) using an in-vitro setup and to compare the findings to those predicted numerically. METHODS: Five idealized AAAs were manufactured using Sylgard 184 silicone rubber, which had been mechanically characterized from tensile tests, tear tests, and finite element analysis. The models were then inflated to the point of rupture and recorded using a high-speed camera. Numerical modeling attempted to confirm these rupture locations. Regional variations in wall thickness of the silicone models was also quantified and applied to numerical models. RESULTS: Four of the 5 models tested ruptured at inflection points in the proximal and distal regions of the aneurysm sac and not at regions of maximum diameter. These findings agree with high stress regions computed numerically. Wall stress appears to be independent of wall thickness, with high stress occurring at regions of inflection regardless of wall thickness variations. CONCLUSION: According to these experimental and numerical findings, AAAs experience higher stresses at regions of inflection compared to regions of maximum diameter. Ruptures of the idealized silicone models occurred predominantly at the inflection points, as numerically predicted. Regions of inflection can be easily identified from basic 3-dimensional reconstruction; as ruptures appear to occur at inflection points, these findings may provide a useful insight into the clinical significance of inflection regions. This approach will be applied to patient-specific models in a future study.

Development of a shear-thinning biomaterial as an endovascular embolic agent for the treatment of type B aortic dissection.

False lumen embolisation is a promising treatment strategy in type B aortic dissection (TBAD) but it is limited by the lack of a disease-specific embolic agent. Our aim was to develop a biomaterial that could be delivered minimally-invasively into the TBAD false lumen and embolise the region. We created 24 shear-thinning biomaterials from blends of gelatin, silicate nanoparticles and silk fibroin, and evaluated their suitability as a false lumen embolic agent in TBAD. We determined the stability of mechanical properties by measuring the compressive modulus of samples stored in physiological conditions over a 21 day period. We quantified injectability by measuring the force required to inject each biomaterial through catheters of varying diameter. We also assessed in vitro degradation rates by measuring weight change over 30 days. Finally, we developed an in vitro experimental pulsatile flow setup with two different anatomically-correct TBAD geometries and performed 78 false lumen occlusion experiments under different operating conditions. We found that the compressive moduli changed rapidly on exposure to 37 °C before stabilising by Day 7. A high silicate nanoparticle to gelatin ratio resulted in greater compressive moduli, with a maximum of 117.6 ±â€¯15.2 kPa. By reducing the total solid concentration, we could improve injectability and biomaterials with 8% (w/v) solids required <80 N force to be injected through a 4.0 mm catheter. Our in vitro degradation rates showed that the biomaterial only degraded by 1.5-8.4% over a 30 day period. We found that the biomaterial could occlude flow to the false lumen in 99% of experiments. In conclusion, blends with high silicate nanoparticle and low silk fibroin content warrant further investigation for their potential as false lumen embolic agents and could be a promising alternative to current TBAD repair methods.

Mechanical behaviour of alginate-gelatin hydrogels for 3D bioprinting.

Hydrogels comprised of alginate and gelatin have demonstrated potential as biomaterials in three dimensional (3D) bioprinting applications. However, as with all hydrogel-based biomaterials used in extrusion-based bioprinting, many parameters influence their performance and there is limited data characterising the behaviour of alginate-gelatin (Alg-Gel) hydrogels. Here we investigated nine Alg-Gel blends by varying the individual constituent concentrations. We tested samples for printability and print accuracy, compressive behaviour and change over time, and viability of encapsulated mesenchymal stem cells in bioprinted constructs. Printability tests showed a decrease in strand width with increasing concentrations of Alg-Gel. However due to the increased viscosity associated with the higher Alg-Gel concentrations, the minimum width was found to be 0.32mm before blends became too viscous to print. Similarly, printing accuracy was increased in higher concentrations, exceeding 90% in some blends. Mechanical properties were assessed through uniaxial compression testing and it was found that increasing concentrations of both Alg and Gel resulted in higher compressive modulus. We also deemed 15min crosslinking in calcium chloride to be sufficient. From our data, we propose a blend of 7%Alg-8%Gel that yields high printability, mechanical strength and stiffness, and cell viability. However, we found the compressive behaviour of Alg-Gel to reduce rapidly over time and especially when incubated at 37°C. Here we have reported relevant data on Alg-Gel hydrogels for bioprinting. We tested for biomaterial properties and show that these hydrogels have many desirable characteristics that are highly tunable. Though further work is needed before practical use in vivo can be achieved.

Characterisation of hyaluronic acid methylcellulose hydrogels for 3D bioprinting.

Hydrogels containing hyaluronic acid (HA) and methylcellulose (MC) have shown promising results for three dimensional (3D) bioprinting applications. However, several parameters influence the applicability bioprinting and there is scarce data in the literature characterising HAMC. We assessed eight concentrations of HAMC for printability, swelling and stability over time, rheological and structural behaviour, and viability of mesenchymal stem cells. We show that HAMC blends behave as viscous solutions at 4°C and have faster gelation times at higher temperatures, typically gelling upon reaching 37°C. We found the storage, loss and compressive moduli to be dependent on HAMC concentration and incubation time at 37°C, and show the compressive modulus to be strain-rate dependent. Swelling and stability was influenced by time, more so than pH environment. We demonstrated that mesenchymal stem cell viability was above 75% in bioprinted structures and cells remain viable for at least one week after 3D bioprinting. The mechanical properties of HAMC are highly tuneable and we show that higher concentrations of HAMC are particularly suited to cell-encapsulated 3D bioprinting applications that require scaffold structure and delivery of cells.

Experimental modelling of aortic aneurysms: novel applications of silicone rubbers.

A range of silicone rubbers were created based on existing commercially available materials. These silicones were designed to be visually different from one another and have distinct material properties, in particular, ultimate tensile strengths and tear strengths. In total, eleven silicone rubbers were manufactured, with the materials designed to have a range of increasing tensile strengths from approximately 2 to 4 MPa, and increasing tear strengths from approximately 0.45 to 0.7 N/mm. The variations in silicones were detected using a standard colour analysis technique. Calibration curves were then created relating colour intensity to individual material properties. All eleven materials were characterised and a 1st order Ogden strain energy function applied. Material coefficients were determined and examined for effectiveness. Six idealised abdominal aortic aneurysm models were also created using the two base materials of the study, with a further model created using a new mixing technique to create a rubber model with randomly assigned material properties. These models were then examined using videoextensometry and compared to numerical results. Colour analysis revealed a statistically significant linear relationship (p<0.0009) with both tensile strength and tear strength, allowing material strength to be determined using a non-destructive experimental technique. The effectiveness of this technique was assessed by comparing predicted material properties to experimentally measured methods, with good agreement in the results. Videoextensometry and numerical modelling revealed minor percentage differences, with all results achieving significance (p<0.0009). This study has successfully designed and developed a range of silicone rubbers that have unique colour intensities and material strengths. Strengths can be readily determined using a non-destructive analysis technique with proven effectiveness. These silicones may further aid towards an improved understanding of the biomechanical behaviour of aneurysms using experimental techniques.