Poly Ester Urethane Scaffolds Research Articles

Electrospun polyester-urethane scaffold preserves mechanical properties and exhibits strain stiffening during in situ tissue ingrowth and degradation

Consistent mechanical performance from implantation through healing and scaffold degradation is highly desired for tissue-regenerative scaffolds, e.g. when used for vascular grafts. The aim of this study was the paired in vivo mechanical assessment of biostable and fast degrading electrospun polyester-urethane scaffolds to isolate the effects of material degradation and tissue formation after implantation. Biostable and degradable polyester-urethane scaffolds with substantial fibre alignment were manufactured by electrospinning. Scaffold samples were implanted paired in subcutaneous position in rats for 7, 14 and 28 days. Morphology, mechanical properties and tissue ingrowth of the scaffolds were assessed before implantation and after retrieval. Tissue ingrowth after 28 days was 83 ± 10% in the biostable scaffold and 77 ± 4% in the degradable scaffold. For the biostable scaffold, the elastic modulus at 12% strain increased significantly between 7 and 14 days and decreased significantly thereafter in fibre but not in cross-fibre direction. The degradable scaffold exhibited a significant increase in the elastic modulus at 12% strain from 7 to 14 days after which it did not decrease but remained at the same magnitude, both in fibre and in cross-fibre direction. Considering that the degradable scaffold loses its material strength predominantly during the first 14 days of hydrolytic degradation (as observed in our previous in vitro study), the consistency of the elastic modulus of the degradable scaffold after 14 days is an indication that the regenerated tissue construct retains its mechanical properties.

Additive manufactured, highly resilient, elastic, and biodegradable poly(ester)urethane scaffolds with chondroinductive properties for cartilage tissue engineering.

Articular cartilage was thought to be one of the first tissues to be successfully engineered. Despite the avascular and non-innervated nature of the tissue, the cells within articular cartilage – chondrocytes – account for a complex phenotype that is difficult to be maintained in vitro. The use of bone marrow–derived stromal cells (BMSCs) has emerged as a potential solution to this issue. Differentiation of BMSCs toward stable and non-hypertrophic chondrogenic phenotypes has also proved to be challenging. Moreover, hyaline cartilage presents a set of mechanical properties – relatively high Young's modulus, elasticity, and resilience – that are difficult to reproduce. Here, we report on the use of additive manufactured biodegradable poly(ester)urethane (PEU) scaffolds of two different structures (500 μm pore size and 90° or 60° deposition angle) that can support the loads applied onto the knee while being highly resilient, with a permanent deformation lower than 1% after 10 compression-relaxation cycles. Moreover, these scaffolds appear to promote BMSC differentiation, as shown by the deposition of glycosaminoglycans and collagens (in particular collagen II). At gene level, BMSCs showed an upregulation of chondrogenic markers, such as collagen II and the Sox trio, to higher or similar levels than that of traditional pellet cultures, with a collagen II/collagen I relative expression of 2–3, depending on the structure of the scaffold. Moreover, scaffolds with different pore architectures influenced the differentiation process and the final BMSC phenotype. These data suggest that additive manufactured PEU scaffolds could be good candidates for cartilage tissue regeneration in combination with microfracture interventions.

Biomimetic engineering of the cardiac tissue through processing, functionalization, and biological characterization of polyester urethanes

Three-dimensional (3D) tissue models offer new tools in the study of diseases. In the case of the engineering of cardiac muscle, a realistic goal would be the design of a scaffold able to replicate the tissue-specific architecture, mechanical properties, and chemical composition, so that it recapitulates the main functions of the tissue. This work is focused on the design and preliminary biological validation of an innovative polyester urethane (PUR) scaffold mimicking cardiac tissue properties. The porous scaffold was fabricated by thermally induced phase separation (TIPS) from poly(ε-caprolactone) diol, 1,4-butanediisocyanate, and l-lysine ethyl ester. Morphological and mechanical scaffolds characterization was accomplished by confocal microscopy, and micro-tensile and compression techniques. Scaffolds were then functionalized with fibronectin by plasma treatment, and the surface treatment was studied by x-ray photoelectron spectroscopy, attenuated total reflectance Fourier transform infrared spectra, and contact angle measurements. Primary rat neonatal cardiomyocytes were seeded on scaffolds, and their colonization, survival, and beating activity were analyzed for 14 days. Signal transduction pathways and apoptosis involved in cells, the structural development of the heart, and its metabolism were analyzed. PUR scaffolds showed a porous-aligned structure and mechanical properties consistent with that of the myocardial tissue. Cardiomyocytes plated on the scaffolds showed a high survival rate and a stable beating activity. Serine/threonine kinase (AKT) and extracellular signal-regulated kinases (ERK) phosphorylation was higher in cardiomyocytes cultured on the PUR scaffold compared to those on tissue culture plates. Real-time polymerase chain reaction analysis showed a significant modulation at 14 days of cardiac muscle (MYH7, prepro-ET-1), hypertrophy-specific (CTGF), and metabolism-related (SLC2a1, PFKL) genes in PUR scaffolds.

Polyesterurethane and acellular matrix based hybrid biomaterial for bladder engineering.

Poly(lactic-co-glycolic acid) (PLGA) based biomaterials for soft tissue engineering have inherent disadvantages, such as a relative rigidity and a limited variability in the mechanical properties and degradation rates. In this study, a novel electrospun biomaterial based on degradable polyesterurethane (PEU) (DegraPol® ) was investigated for potential use for bladder engineering in vitro and in vivo. Hybrid microfibrous PEU and PLGA scaffolds were produced by direct electrospinning of the polymer onto a bladder acellular matrix. The scaffold morphology of the scaffold was analyzed, and the biological performance was tested in vitro and in vivo using a rat cystoplasty model. Anatomical and functional outcomes after implantation were analyzed macroscopically, histologically and by cystometry, respectively. Scanning electron microscopy analysis showed that PEU samples had a lower porosity (p < 0.001) and were slightly thinner (p = 0.009) than the PGLA samples. Proliferation and survival of the seeded smooth muscle cells in vitro were comparable on PEU and PLGA scaffolds. After 8 weeks in vivo, the PEU scaffolds exhibited no shrinkage. However, cystometry of the reconstructed bladders exhibited a slightly greater functional bladder capacity in the PLGA group. Morphometric analyses revealed significantly better tissue healing (p < 0.05) and, in particular, better smooth muscle regeneration, as well as a lower rate of inflammatory responses at 8 weeks in the PEU group. Collectively, the results indicated that PEU-hybrid scaffolds promote bladder tissue formation with excellent tissue integration and a low inflammatory reaction in vivo. PEU is a promising biomaterial, particularly with regard to functional tissue engineering of the bladder and other hollow organs. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 658-667, 2017.

The anisotropic mechanical behaviour of electro-spun biodegradable polymer scaffolds: Experimental characterisation and constitutive formulation

Electro-spun biodegradable polymer fibrous structures exhibit anisotropic mechanical properties dependent on the degree of fibre alignment. Degradation and mechanical anisotropy need to be captured in a constitutive formulation when computational modelling is used in the development and design optimisation of such scaffolds.Biodegradable polyester-urethane scaffolds were electro-spun and underwent uniaxial tensile testing in and transverse to the direction of predominant fibre alignment before and after in vitro degradation of up to 28 days. A microstructurally-based transversely isotropic hyperelastic continuum constitutive formulation was developed and its parameters were identified from the experimental stress–strain data of the scaffolds at various stages of degradation.During scaffold degradation, maximum stress and strain in circumferential direction decreased from 1.02±0.23MPa to 0.38±0.004MPa and from 46±11% to 12±2%, respectively. In longitudinal direction, maximum stress and strain decreased from 0.071±0.016MPa to 0.010±0.007MPa and from 69±24% to 8±2%, respectively. The constitutive parameters were identified for both directions of the non-degraded and degraded scaffold for strain range varying between 0% and 16% with coefficients of determination r2>0.871. The six-parameter constitutive formulation proved versatile enough to capture the varying non-linear transversely isotropic behaviour of the fibrous scaffold throughout various stages of degradation.

Skeletal myogenesis on highly orientated microfibrous polyesterurethane scaffolds

Skeletal myogenesis is a complex process, which is known to be intimately depending on an optimal outside-in substrate-cell signaling. Current attempts to reproduce skeletal muscle tissue in vitro using traditional scaffolds mainly suffer from poor directionality of the myofibers, resulting in an ineffective vectorial power generation. In this study, we aimed at investigating skeletal myogenesis on novel biodegradable microfibrous scaffolds made of DegraPol, a block polyesterurethane previously demonstrated to be suitable for this application. DegraPol was processed by electrospinning in the form of highly orientated ("O") and nonorientated ("N/O") microfibrous meshes and by solvent-casting in the form of nonporous films ("F"). The effect of the fiber orientation at the scaffold surface was evaluated by investigating C2C12 and L6 proliferation (via SEM analysis and alamarBlue test) and differentiation (via RT-PCR analysis and MHC immunostaining). We demonstrated that highly orientated elastomeric microfibrous DegraPol scaffolds enable skeletal myogenesis in vitro by aiding in (a) myoblast adhesion, (b) myotube alignment, and (c) noncoplanar arrangement of cells, by providing the necessary directional cues along with architectural and mechanical support.

Enhancing sealing of fetal membrane defects using tissue engineered native amniotic scaffolds in the rabbit model

The purpose of this study was to compare the efficacy of native engineered amniotic scaffolds (AS) and polyesterurethane scaffolds (DegraPol) and document wound healing response when sealing iatrogenic fetal membrane defects in the rabbit model. Native AS were engineered from freshly harvested membranes of 23 days' gestational age (GA; term = 31-2 d). Acellularity of AS was assessed by histology, light and scanning electron microscopy. Fetal membrane defects were created by 14 gauge-needle puncture at GA 23 days and primarily closed with AS (n = 10) or DegraPol (n = 10) or left unclosed (positive controls; n = 10). Sixty-one sacs served as negative controls. At GA 30 days a second look hysterotomy was performed to assess presence of amniotic fluid (AF) and harvest plugging sites for microscopic evaluation. Engineered AS had a cell-free collagenous fiber network. AF was significantly higher only in the DegraPol group (78%; P < .05) compared to the AF in positive controls (17%). Integration of plugs in the fetal membrane defect was better with AS than DegraPol, with higher reepithelialization rates (AS: 52.5% +/- 6.5%; DegraPol: 11.6% +/- 2.6%; P < .001) and proliferation indices (AS: 0.47 +/- 0.03; DegraPol: 0.28 +/- 0.04; P = .001). In both treatment groups, cell proliferation in the myometrium was increased (P < .05). Native AS seal iatrogenic fetal membrane defects better than DegraPol. Within a week, there is abundant reepithelilization and minimal local inflammation. This yields the proof of principle that engineered native, amniotic membrane scaffolds enhance fetal membrane wound healing response.

Enhancing sealing of fetal membrane defects using tissue engineered native amniotic scaffolds in the rabbit model

To compare the efficacy of native engineered amniotic scaffolds (AS) and polyesterurethane scaffolds (DegraPol) and document wound healing response when sealing iatrogenic fetal membrane defects in the rabbit model. Native AS were engineered from freshly harvested membranes of 23d gestational age (GA; term=31-2d). Acellularity of AS was assessed by histology, light and scanning electron microscopy. Fetal membrane defects were created by 14 gauge-needle puncture at GA=23d and primarily closed with AS (n=10) or DegraPol(n=10) or left unclosed (positive controls; n=10). Sixty-one sacs served as negative controls. At GA=30 days a second look hysterotomy was performed to assess presence of amniotic fluid (AF) and harvest plugging sites for microscopic evaluation. Engineered AS had a cell-free collagenous fiber network. AF tended to be, or was higher in the AS (67%; P=.07) or DegraPol group (78%; P<.05) as compared to positive controls (17%). Integration of plugs in the fetal membrane defect was better with AS than DegraPol, with higher re-epithelialization rates (AS: 52.5%±6.5%; DegraPol: 11.6%±2.6; P<.001) and proliferation indices (AS: 0.47±0.03, DegraPol: 0.28±0.04; P=.001). In both treatment groups, cell proliferation in the myometrium was increased (P<.05). Native AS seal iatrogenic fetal membrane defect better than DegraPol. Within a week, there is abundant re-epithelilization and minimal local inflammation. This yields the proof of principle that engineered native, amniotic membrane scaffolds enhance fetal membrane wound healing response.