Forefront Research of Foaming Strategies on Biodegradable Polymers and Their Composites by Thermal or Melt-Based Processing Technologies: Advances and Perspectives.

The last few decades have witnessed significant advances in the development of polymeric-based foam materials. These materials find several practical applications in our daily lives due to their characteristic properties such as low density, thermal insulation, and porosity, which are important in packaging, in building construction, and in biomedical applications, respectively. The first foams with practical applications used polymeric materials of petrochemical origin. However, due to growing environmental concerns, considerable efforts have been made to replace some of these materials with biodegradable polymers. Foam processing has evolved greatly in recent years due to improvements in existing techniques, such as the use of supercritical fluids in extrusion foaming and foam injection moulding, as well as the advent or adaptation of existing techniques to produce foams, as in the case of the combination between additive manufacturing and foam technology. The use of supercritical CO2 is especially advantageous in the production of porous structures for biomedical applications, as CO2 is chemically inert and non-toxic; in addition, it allows for an easy tailoring of the pore structure through processing conditions. Biodegradable polymeric materials, despite their enormous advantages over petroleum-based materials, present some difficulties regarding their potential use in foaming, such as poor melt strength, slow crystallization rate, poor processability, low service temperature, low toughness, and high brittleness, which limits their field of application. Several strategies were developed to improve the melt strength, including the change in monomer composition and the use of chemical modifiers and chain extenders to extend the chain length or create a branched molecular structure, to increase the molecular weight and the viscosity of the polymer. The use of additives or fillers is also commonly used, as fillers can improve crystallization kinetics by acting as crystal-nucleating agents. Alternatively, biodegradable polymers can be blended with other biodegradable polymers to combine certain properties and to counteract certain limitations. This work therefore aims to provide the latest advances regarding the foaming of biodegradable polymers. It covers the main foaming techniques and their advances and reviews the uses of biodegradable polymers in foaming, focusing on the chemical changes of polymers that improve their foaming ability. Finally, the challenges as well as the main opportunities presented reinforce the market potential of the biodegradable polymer foam materials.

COX-2 inhibitor delivery system aiming intestinal inflammatory disorders.

Selective COX-2 inhibitors such as etoricoxib (ETX) are potentially indicated for the treatment of intestinal inflammatory disorders. However, their systemic administration provokes some off-site secondary effects, decreasing the desirable local effectiveness. To circumvent such limitations, herein an ETX delivery system based on electrospun fibrous meshes (eFMs) was proposed. ETX at different concentrations (1, 2, and 3 mg mL-1) was loaded into eFMs, which not affect the morphology and the mechanical properties of this drug delivery system (DDS). The ETX showed a burst release within the first 12 h, followed by a faster release until 36 h, gradually decreasing over time. Importantly, the ETX studied concentrations were not toxic to human colonic cells (i.e. epithelial and fibroblast). Moreover, the DDS loading the highest concentration of ETX, when tested with stimulated human macrophages, promoted a reduction of PGE2, IL-8 and TNF-α secretion. Therefore, the proposed DDS may constitute a safe and efficient treatment of colorectal diseases promoted by inflammatory disorders associated with COX-2.

Chitosan/Virgin-Coconut-Oil-Based System Enriched with Cubosomes: A 3D Drug-Delivery Approach.

Emulsion-based systems that combine natural polymers with vegetable oils have been identified as a promising research avenue for developing structures with potential for biomedical applications. Herein, chitosan (CHT), a natural polymer, and virgin coconut oil (VCO), a resource obtained from coconut kernels, were combined to create an emulsion system. Phytantriol-based cubosomes encapsulating sodium diclofenac, an anti-inflammatory drug, were further dispersed into CHT/VCO- based emulsion. Then, the emulsions were frozen and freeze-dried to produce scaffolds. The scaffolds had a porous structure ranging from 20.4 to 73.4 µm, a high swelling ability (up to 900%) in PBS, and adequate stiffness, notably in the presence of cubosomes. Moreover, a well-sustained release of the entrapped diclofenac in the cubosomes into the CHT/VCO-based system, with an accumulated release of 45 ± 2%, was confirmed in PBS, compared to free diclofenac dispersed (80 ± 4%) into CHT/VCO-based structures. Overall, the present approach opens up new avenues for designing porous biomaterials for drug delivery through a sustainable pathway.

Advanced Polymeric Membranes as Biomaterials Based on Marine Sources Envisaging the Regeneration of Human Tissues.

The self-repair capacity of human tissue is limited, motivating the arising of tissue engineering (TE) in building temporary scaffolds that envisage the regeneration of human tissues, including articular cartilage. However, despite the large number of preclinical data available, current therapies are not yet capable of fully restoring the entire healthy structure and function on this tissue when significantly damaged. For this reason, new biomaterial approaches are needed, and the present work proposes the development and characterization of innovative polymeric membranes formed by blending marine origin polymers, in a chemical free cross-linking approach, as biomaterials for tissue regeneration. The results confirmed the production of polyelectrolyte complexes molded as membranes, with structural stability resulting from natural intermolecular interactions between the marine biopolymers collagen, chitosan and fucoidan. Furthermore, the polymeric membranes presented adequate swelling ability without compromising cohesiveness (between 300 and 600%), appropriate surface properties, revealing mechanical properties similar to native articular cartilage. From the different formulations studied, the ones performing better were the ones produced with 3 % shark collagen, 3% chitosan and 10% fucoidan, as well as with 5% jellyfish collagen, 3% shark collagen, 3% chitosan and 10% fucoidan. Overall, the novel marine polymeric membranes demonstrated to have promising chemical, and physical properties for tissue engineering approaches, namely as thin biomaterial that can be applied over the damaged articular cartilage aiming its regeneration.

Development of bilayered porous silk scaffolds for thymus bioengineering.

The thymus coordinates the development and selection of T cells. It is structured into two main compartments: the cortex and the medulla. The replication of such complex 3D environment has been challenged by bioengineering approaches. Nevertheless, the effect of the scaffold microstructure on thymic epithelial cell (TEC) cultures has not been deeply investigated. Here, we developed bilayered porous silk fibroin scaffolds and tested their effect on TEC co-cultures. The small and large pore scaffolds presented a mean pore size of 84.33 ± 21.51 µm and 194.90 ± 61.38 µm, respectively. The highly porous bilayered scaffolds presented a high water absorption and water content (> 94 %), together with mechanical properties in the range of the native tissue. TEC (i.e., medullary (mTEC) and cortical (cTEC) cell lines) proliferation is increased in scaffolds with larger pores. The co-culture of both TEC lines in the bilayered porous silk scaffolds presents enhanced cell proliferation and metabolic activity when compared with mTEC in single culture. Also, when the co-culture occurred with cTEC in the small pores layer and mTEC in the large pores layer, a 9.2- and 18.9-fold increase in Foxn1 and Icam1 gene expression in cTEC is evident. These results suggest that scaffold microstructure and the co-culture influence TEC's behaviour. Bilayered silk scaffolds with adjusted microstructure are a valid alternative for TEC culture, having possible applications in advanced thymus bioengineering strategies.

Structure and Composition of the Cuticle of the Goose Barnacle Pollicipes pollicipes: A Flexible Composite Biomaterial.

Arthropods, the largest animal phylum, including insects, spiders and crustaceans, are characterized by their bodies being covered primarily in chitin. Besides being a source of this biopolymer, crustaceans have also attracted attention from biotechnology given their cuticles' remarkable and diverse mechanical properties. The goose barnacle, Pollicipes pollicipes, is a sessile crustacean characterized by their body parts covered with calcified plates and a peduncle attached to a substrate covered with a cuticle. In this work, the composition and structure of these plates and cuticle were characterized. The morphology of the tergum plate revealed a compact homogeneous structure of calcium carbonate, a typical composition among marine invertebrate hard structures. The cuticle consisted of an outer zone covered with scales and an inner homogenous zone, predominantly organic, composed of successive layers parallel to the surface. The scales are similar to the tergum plate and are arranged in parallel and oriented semi-vertically. Structural and biochemical characterization confirmed a bulk composition of ɑ-chitin and suggested the presence of elastin-based proteins and collagen. The mechanical properties of the cuticle showed that the stiffness values are within the range of values described in elastomers and soft crustacean cuticles resulting from molting. The removal of calcified components exposed round holes, detailed the structure of the lamina, and changed the protein properties, increasing the rigidity of the material. This flexible cuticle, predominantly inorganic, can provide bioinspiration for developing biocompatible and mechanically suitable biomaterials for diverse applications, including in tissue engineering approaches.

Development of Cork Biocomposites Enriched with Chitosan Targeting Antibacterial and Antifouling Properties.

The demand for bio-based and safer composite materials is increasing due to the growth of the industry, human population, and environmental concerns. In this framework, sustainable and safer cork-polymer composites (CPC), based on green low-density polyethylene (LDPE) were developed using melt-based technologies. Chitosan and polyethylene-graft-maleic anhydride (PE-g-MA) were employed to enhance the CPC's properties. The morphology, wettability, mechanical, thermal, and antibacterial properties of the CPC against Pseudomonas putida (P. putida) and Staphylococcus aureus (S. aureus) were examined. The CPC showed improved stiffness when compared with that of the LDPE matrix, preferably when combined with chitosan and PE-g-MA (5 wt. %), reinforcing the stiffness (58.8%) and the strength (66.7%). Chitosan also increased the composite stiffness and strength, as well as reduced the surface hydrophilicity. The CPCs' antibacterial activity revealed that cork significantly reduces the biofilm on the polymer matrix. The highest biofilm reduction was found with CPC containing cork and 5 wt. % chitosan for both P. putida (54% reduction) and S. aureus (36% reduction), confirming their potential to extend the lifespan of products for packaging and healthcare, among other applications. This work leads to the understanding of the factors that influence biofilm formation in cork composites and provides a strategy to reinforce their behavior using chitosan.

Cell-Laden Marine Gelatin Methacryloyl Hydrogels Enriched with Ascorbic Acid for Corneal Stroma Regeneration.

Corneal pathologies from infectious or noninfectious origin have a significant impact on the daily lives of millions of people worldwide. Despite the risk of organ rejection or infection, corneal transplantation is currently the only effective treatment. Finding safe and innovative strategies is the main goal of tissue-engineering-based approaches. In this study, the potential of gelatin methacryloyl (GelMA) hydrogels produced from marine-derived gelatin and loaded with ascorbic acid (as an enhancer of the biological activity of cells) was evaluated for corneal stromal applications. Marine GelMA was synthesized with a methacrylation degree of 75%, enabling effective photocrosslinking, and hydrogels with or without ascorbic acid were produced, encompassing human keratocytes. All the produced formulations exhibited excellent optical and swelling properties with easy handling as well as structural stability and adequate degradation rates that may allow proper extracellular matrix remodeling by corneal stromal cells. Formulations loaded with 0.5 mg/mL of ascorbic acid enhanced the biological performance of keratocytes and induced collagen production. These results suggest that, in addition to marine-derived gelatin being suitable for the synthesis of GelMA, the hydrogels produced are promising biomaterials for corneal regeneration applications.

Collagen membrane from bovine pericardium for treatment of long bone defect.

The treatment of bone regeneration failures has been constantly improved with the study of new biomaterials. Techgraft® is a collagen membrane derived from bovine pericardium, which has been shown to have biocompatibility and effectiveness in tissue repair. However, its use in orthopedics has not yet been evaluated. Therefore, the purpose of this study was to characterize a bovine pericardium collagen membrane and evaluate the effects of its use in the regeneration of a bone defect in rat tibia. Scanning electron microscopy, atomic force microscopy, weight lost and water uptake tests, and mechanical test were performed. Afterwards, the membrane was tested in an experimental study, using 12 male Sprague Dawley rats. A bone defect was surgically made in tibiae of animals, which were assigned to two groups (n = 6): bone defect treated with collagen membrane (TG) and bone defect without treatment (CONT). Then, tibiae were submitted to micro-CT. The membranes preserved their natural collagen characteristics, presenting great strength, high water absorption, hydrophilicity, and almost complete dissolution in 30 days. In the experimental study, the membrane enhanced the growth of bone tissue in contact with its surface. A higher bone volume and trabeculae number and less trabecular space was observed in bone defects of the membrane group compared to the control group at 21 days. In conclusion, the Techgraft membrane seems to have favorable characteristics for treatment of long bone repair.

Untangling the biological and inflammatory behavior of silk-like sutures In vivo.

Recombinant spider silk materials with antimicrobial peptides are a promising new class of drug-free antimicrobial materials capable of preventing surgical site infections (SSI), but their potential to impede infections is unclear. Herein, we aimed to unravel the biological and inflammatory potential of bioengineered spider silk materials to prevent SSI using an infection animal model. Silk-like fibers made of silk fibroin and spider silk proteins with antimicrobial peptides (6mer-HNP1) held improved stiffness (2.9 GPa) and had a slow biodegradation profile while inhibiting bacterial adherence in vitro by 5-log and 6-log reduction on Methicillin-Resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), respectively. In vivo studies showed that fibers with 6mer-HNP1 elicited a short-term low to mild local inflammatory response, similar to implanted commercial sutures. In the presence of a bacterial infection, the mediators related to infection and inflammation were downregulated suggesting that the fibers maintained a low but active response to bacterial infection. Thus, the presence of 6mer-HNP1 helped the host maintain an active response to bacterial infection, impairing the development of an acute infection. Our findings further support the use of bioengineered spider silk proteins to develop drug-free antimicrobial sutures capable to impair SSI.

Assessing the combined effect of surface topography and substrate rigidity in human bone marrow stem cell cultures.

The combined effect of surface topography and substrate rigidity in stem cell cultures is still under-investigated, especially when biodegradable polymers are used. Herein, we assessed human bone marrow stem cell response on aliphatic polyester substrates as a function of anisotropic grooved topography and rigidity (7 and 12 kPa). Planar tissue culture plastic (TCP, 3 GPa) and aliphatic polyester substrates were used as controls. Cell morphology analysis revealed that grooved substrates caused nuclei orientation/alignment in the direction of the grooves. After 21 days in osteogenic and chondrogenic media, the 3 GPa TCP and the grooved 12 kPa substrate induced significantly higher calcium deposition and alkaline phosphatase (ALP) activity and glycosaminoglycan (GAG) deposition, respectively, than the other groups. After 14 days in tenogenic media, the 3 GPa TCP upregulated four and downregulated four genes; the planar 7 kPa substrate upregulated seven genes and downregulated one gene; and the grooved 12 kPa substrate upregulated seven genes and downregulated one gene. After 21 days in adipogenic media, the softest (7 kPa) substrates induced significantly higher oil droplet deposition than the other substrates and the grooved substrate induced significantly higher droplet deposition than the planar. Our data pave the way for more rational design of bioinspired constructs.

Pharmacological and Non-Pharmacological Agents versus Bovine Colostrum Supplementation for the Management of Bone Health Using an Osteoporosis-Induced Rat Model.

Osteoporosis is defined by loss of bone mass and deteriorated bone microarchitecture. The present study compared the effects of available pharmacological and non-pharmacological agents for osteoporosis [alendronate (ALE) and concomitant supplementation of vitamin D (VD) and calcium (Ca)] with the effects of bovine colostrum (BC) supplementation in ovariectomized (OVX) and orchidectomized (ORX) rats. Seven-month-old rats were randomly allocated to: (1) placebo-control, (2) ALE group (7.5 µg/kg of body weight/day/5 times per week), (3) VD/Ca group (VD: 35 µg/kg of body weight/day/5 times per week; Ca: 13 mg/kg of body weight/day/3 times per week), and (4) BC supplementation (OVX: 1.5 g/day/5 times per week; ORX: 2 g/day/5 times per week). Following four months of supplementation, bone microarchitecture, strength and bone markers were evaluated. ALE group demonstrated significantly higher Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC and significantly lower Ct.Pr, Tb.Pr, Tb.Sp, Ct.BMD and Tb.BMD, compared to placebo (p < 0.05). BC presented significantly higher Ct.Pr, Ct.BMD, Tb.Pr, Tb.Sp, and Tb.BMD and significantly lower Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC compared to ALE in OVX rats (p < 0.05). OVX rats receiving BC experienced a significant increase in serum ALP and OC levels post-supplementation (p < 0.05). BC supplementation may induce positive effects on bone metabolism by stimulating bone formation, but appear not to be as effective as ALE.

Tailoring Natural-Based Oleogels Combining Ethylcellulose and Virgin Coconut Oil.

Oleogels are becoming an attractive research field, since they have recently been shown to be feasible for the food and pharmaceutical sectors and provided some insights into the biomedical area. In this work, edible oleogels were tailored through the combination of ethylcellulose (EC), a gelling agent, with virgin coconut oil (VCO), vegetable oil derived from coconut. The influence of the different EC and VCO ratios on the structural, physical, and thermal properties of the oleogels was studied. All EC/VCO-based oleogels presented a stable network with a viscoelastic nature, adequate structural stability, modulable stiffness, high oil-binding capability, antioxidant activity, and good thermal stability, evidencing the EC and VCO's good compatibility.

Silk fibroin/cholinium gallate-based architectures as therapeutic tools.

The combination of natural resources with biologically active biocompatible ionic liquids (Bio-IL) is presented as a combinatorial approach for developing tools to manage inflammatory diseases. Innovative biomedical solutions were constructed combining silk fibroin (SF) and Ch[Gallate], a Bio-IL with antioxidant and anti-inflammatory features, as freeze-dried 3D-based sponges. An evaluation of the effect of the Ch[Gallate] concentration (≤3% w/v) on the SF/Ch[Gallate] sponges was studied. Structural changes observed on the sponges revealed that the Ch[Gallate] presence positively affected the ß-sheet formation while not influencing the silk native structure, which was suggested by the FTIR and solid-state NMR results, respectively. Also, it was possible to modulate their mechanical properties, antioxidant activity and stability/degradation in an aqueous environment, by changing the Ch[Gallate] concentration. The architectures showed high water uptake ability and a weight loss that follows the controlled Ch[Gallate] release rate studied for 7 days. Furthermore, the sponges supported human adipose stem cells growth and proliferation, up to 7 days. TNF-α, IL-6 (pro-inflammatory) and IL-10 (anti-inflammatory) release quantification from a human monocyte cell line revealed a decrease in the pro-inflammatory cytokines concentrations in samples containing Ch[Gallate]. These outcomes encourage the use of the developed architectures as tissue engineering solutions, potentially targeting inflammation processes. STATEMENT OF SIGNIFICANCE: Combining natural resources with active biocompatible ionic liquids (Bio-IL) is herein presented as a combinatorial approach for the development of tools to manage inflammatory diseases. We propose using silk fibroin (SF), a natural protein, with cholinium gallate, a Bio-IL, with antioxidant and anti-inflammatory properties, to construct 3D-porous sponges through a sustainable methodology. The morphological features, swelling, and stability of the architectures were controlled by Bio-IL content in the matrices. The sponges were able to support human adipose stem cells growth and proliferation, and their therapeutic effect was proved by the blockage of TNF-α from activated and differentiated THP-1 monocytes. We believe that these bio-friendly and bioactive SF/Bio-IL-based sponges are effective for targeting pathologies with associated inflammatory processes.

Chitosan/ß-TCP composites scaffolds coated with silk fibroin: a bone tissue engineering approach.

Bone regeneration and natural repair are long-standing processes that can lead to uneven new tissue growth. By introducing scaffolds that can be autografts and/or allografts, tissue engineering provides new approaches to manage the major burdens involved in this process. Polymeric scaffolds allow the incorporation of bioactive agents that improve their biological and mechanical performance, making them suitable materials for bone regeneration solutions. The present work aimed to create chitosan/beta-tricalcium phosphate-based scaffolds coated with silk fibroin and evaluate their potential for bone tissue engineering. Results showed that the obtained scaffolds have porosities up to 86%, interconnectivity up to 96%, pore sizes in the range of 60-170 µm, and a stiffness ranging from 1 to 2 MPa. Furthermore, when cultured with MC3T3 cells, the scaffolds were able to form apatite crystals after 21 d; and they were able to support cell growth and proliferation up to 14 d of culture. Besides, cellular proliferation was higher on the scaffolds coated with silk. These outcomes further demonstrate that the developed structures are suitable candidates to enhance bone tissue engineering.

Bovine Colostrum Supplementation Improves Bone Metabolism in an Osteoporosis-Induced Animal Model.

Osteoporosis is characterized by bone loss. The present study aims to investigate the effects of bovine colostrum (BC) on bone metabolism using ovariectomized (OVX) and orchidectomized (ORX) rat models. Twenty-seven-week-old Wistar Han rats were randomly assigned as: (1) placebo control, (2) BC supplementation dose 1 (BC1: 0.5 g/day/OVX, 1 g/day/ORX), (3) BC supplementation dose 2 (BC2: 1 g/day/OVX, 1.5 g/day/ORX) and (4) BC supplementation dose 3 (BC3: 1.5 g/day/OVX, 2 g/day/ORX). Bone microarchitecture, strength, gene expression of VEGFA, FGF2, RANKL, RANK and OPG, and bone resorption/formation markers were assessed after four months of BC supplementation. Compared to the placebo, OVX rats in the BC1 group exhibited significantly higher cortical bone mineral content and trabecular bone mineral content (p < 0.01), while OVX rats in the BC3 group showed significantly higher trabecular bone mineral content (p < 0.05). ORX rats receiving BC dose 2 demonstrated significantly higher levels of trabecular bone mineral content (p < 0.05). Serum osteocalcin in the ORX was pointedly higher in all BC supplementation groups than the placebo (BC1: p < 0.05; BC2, BC3: p < 0.001). Higher doses of BC induced significantly higher relative mRNA expression of OPG, VEGFA, FGF2 and RANKL (p < 0.05). BC supplementation improves bone metabolism of OVX and ORX rats, which might be associated with the activation of the VEGFA, FGF2 and RANKL/RANK/OPG pathways.

An Overview of the Antimicrobial Properties of Lignocellulosic Materials.

Pathogenic microbes are a major source of health and environmental problems, mostly due to their easy proliferation on most surfaces. Currently, new classes of antimicrobial agents are under development to prevent microbial adhesion and biofilm formation. However, they are mostly from synthetic origin and present several disadvantages. The use of natural biopolymers such as cellulose, hemicellulose, and lignin, derived from lignocellulosic materials as antimicrobial agents has a promising potential. Lignocellulosic materials are one of the most abundant natural materials from renewable sources, and they present attractive characteristics, such as low density and biodegradability, are low-cost, high availability, and environmentally friendly. This review aims to provide new insights into the current usage and potential of lignocellulosic materials (biopolymer and fibers) as antimicrobial materials, highlighting their future application as a novel drug-free antimicrobial polymer.

Engineering 3D printed bioactive composite scaffolds based on the combination of aliphatic polyester and calcium phosphates for bone tissue regeneration.

In this study, polylactic acid (PLA) filled with hydroxyapatite (HA) or beta-tricalcium phosphate (TCP) in 5 wt% and 10 wt% of concentration were produced employing twin-screw extrusion followed by fused filament fabrication in two different architectures, varying the orientation of fibers of adjacent layers. The extruded 3D filaments presented suitable rheological and thermal properties to manufacture of 3D scaffolds envisaging bone tissue engineering. The produced scaffolds exhibited a high level of printing accuracy related to the 3D model; confirmed by micro-CT and electron microscopy analysis. The developed architectures presented mechanical properties compatible with human bone replacement. The addition of HA and TCP made the filaments bioactive, and the deposition of new calcium phosphates was observed upon 7 days of incubation in simulated body fluid, exemplifying a microenvironment suitable for cell attachment and proliferation. After 7 days of cell culture, the constructs with a higher percentage of HA and TCP demonstrated a significantly superior amount of DNA when compared to neat PLA, indicating that higher concentrations of HA and TCP could guide a good cellular response and increasing cell cytocompatibility. Differentiation tests were performed, and the biocomposites of PLA/HA and PLA/TCP exhibited earlier markers of cell differentiation as confirmed by alkaline phosphatase and alizarin red assays. The 3D printed composite scaffolds, manufactured with bioactive materials and adequate porous size, supported cell attachment, proliferation, and differentiation, which together with their scalability, promise a high potential for bone tissue engineering applications.

Physicochemical features assessment of acemannan-based ternary blended films for biomedical purposes.

The exploitation of natural origin macromolecules, as complex physical mixtures or drugs, increases in biomedical or tissue engineering (TE) solutions. Aloe Vera is a highly explored medicinal plant, from which the main polysaccharide is acemannan (ACE). The ACE combination with chitosan and alginate results in interactions that lead to mixed junction zones formation, predicting membrane functionality improvement. This work proposes the development and characterization of ACE-based blended films as a promising strategy to design a nature-derived bioactive platform. The results confirmed that stable complex polyelectrolyte structures were formed through different intermolecular interactions. The films present good dimensional stability, flexibility, an adequate swelling ability with mostly radial water uptake, and a sustainable ACE release to the medium. Positive biological performance of the ACE-based blended films with L929 cells also suggested that they can be applied in TE solutions, with the potential to act as bioactive topical platforms.

Development and characterisation of cytocompatible polyester substrates with tunable mechanical properties and degradation rate.

Although it has been repeatedly indicated the importance to develop implantable devices and cell culture substrates with tissue-specific rigidity, current commercially available products, in particular cell culture substrates, have rigidity values well above most tissues in the body. Herein, six resorbable polyester films were fabricated using compression moulding with a thermal presser into films with tailored stiffness by appropriately selecting the ratio of their building up monomers (e.g. lactide, glycolide, trimethylene carbonate, dioxanone, ε-caprolactone). Typical NMR and FTIR spectra were obtained, suggesting that the fabrication process did not have a negative effect on the conformation of the polymers. Surface roughness analysis revealed no apparent differences between the films as a function of polymer composition. Subject to polymer composition, polymeric films were obtained with glass transition temperatures from -52 °C to 61 °C; contact angles in water from 81 ° to 94 °; storage modulus from 108 MPa to 2,756 MPa and loss modulus from 8 MPa to 507 MPa (both in wet state, at 1 Hz frequency and at 37 °C); ultimate tensile strength from 8 MPa to 62 MPa, toughness from 23 MJ/m3 to 287 MJ/m3, strain at break from 3 % to 278 %, macro-scale Young's modulus from 110 MPa to 2,184 MPa (all in wet state); and nano-scale Young's modulus from 6 kPa to 15,019 kPa (in wet state). With respect to in vitro degradation in phosphate buffered saline at 37 °C, some polymeric films [e.g. poly(glycolide-lactide) 30 / 70] started degrading from day 7 (shortest timepoint assessed), whilst others [e.g. poly(glycolide-co-ε-caprolactone) 10 / 90] were more resilient to degradation up to day 21 (longest timepoint assessed). In vitro biological analysis using human dermal fibroblasts and a human monocyte cell line (THP-1) showed the potential of the polymeric films to support cell growth and controlled immune response. Evidently, the selected polymers exhibited properties suitable for a range of clinical indications.