Coaxial electrospinning is a technique that allows the production of nanofibers with a core–shell structure. Such fibers present several advantages as materials for the preparation of scaffolds, namely due to the possibility of combining a core with the desired mechanical properties with a shell prepared from biocompatible materials that will establish proper interactions with the host. Herein, core-shell fibrous meshes, composed of a polycaprolactone (PCL) core and a functionalized gelatin shell, were prepared by coaxial electrospinning and then photocrosslinked under UV light aiming to be used in vascular tissue regeneration. The suitability of the meshes for the pretended biomedical application was evaluated by assessing their chemical/physical properties as well as their haemo and biocompatibility in vitro. The obtained results revealed that meshes’ shell prepared with a higher content of gelatin showed fibers with diameters presenting a unimodal distribution and a mean value of 600 nm. Moreover, those fibers with higher content of gelatin also displayed lower water contact angles, and therefore higher hydrophilicities. Such features are crucial for the good biologic performance displayed by these meshes, when in contact with blood and with Normal Human Dermal Fibroblasts cells.

Polycaprolactone (PCL) and PCL-based materials are widely applied in the biomedical field, however, their slow biodegradation profile makes them more suitable to be used in hard tissues, where healing requires longer periods of time. In order to adjust their properties to suit for soft tissues applications, PCL can be blended with other biodegradable materials in order to tune its degradation rate. Herein, polymeric blends of PCL and castor oil (CO) were prepared after their chemical modification with 2-isocyanatoethylmethacrylate (IEMA) in order to be applied as photocrosslinkable tissue adhesives. These functionalized macromers were chemically characterized and used to prepare polymeric blends (PCL-IEMA/CO-IEMA) with variable mass proportions. A biocompatible photoinitiator (Irgacure 2959) was added to these macromers blends which were then irradiated under UV light. The feasibility of the prepared materials as tissue adhesives was evaluated by assessment of their chemical/physical properties as well as their interaction with blood. Moreover, their cytotoxic profile was also evaluated through in vitro studies using human dermal fibroblasts as model cells.

Cardiovascular disease is the leading cause of morbidity and mortality among industrialized countries. Vascular grafts are often required for the surgical treatments. Considering the limitations associated with the use of autografts and with the currently available synthetic materials, a growing demand in tissue engineered vascular grafts has been registered. During the work here described, electrospinning technique was used to prepared fibrous matrices to be applied as vascular implants. For that purpose, electrospun polycaprolactone (PCL) fibrous mats were produced and afterwards coated with different hydrogel formulations based in photocrosslinkable gelatin (GelMA) and the macromers poly(ethylene glycol) acrylate (PEGA) and poly(ethylene glycol) diacrylate (PEGDA). These were further photocrosslinked under UV irradiation using Irgacure® 2959 (by BASF) as the photoinitiator. The suitability of the coated scaffolds for the intended application, was evaluated by assessing their chemical/physical properties as well as their interaction with blood and endothelial cells.

UV curable adhesives offer major advantages in comparison to other polymeric based adhesive systems, such as fast-curing rate and control of the polymerization heat evolution, being ideal for application on damaged tissues. Herein, functionalized polymers were prepared by modifying polycaprolactone diol (PCL) with an isocyanate-functional unsaturated acrylic ester, Laromer® 9000, using two different proportions. These functionalized materials were chemically/physically characterized and, after the addition of a biocompatible photoinitiator (Irgacure® 2959), were crosslinked by UV light irradiation. Such procedure allows the obtention of flexible transparent films. Films’ properties such as swelling, hydrolytic degradation, thermal stability, surface energy and adhesive capacity were evaluated. Furthermore, to assess the applicability of the films in biomedical applications, their haemocompatibility and biocompatibility were determined using human dermal fibroblasts as model.

Electrospun polymeric meshes are known to exhibit promising properties for the regeneration of several soft tissues. Herein, electrospun polymeric meshes were prepared from blends of polycaprolactone and functionalized gelatin. The meshes were then photocrosslinked under UV light using Irgacure® 2959 as the photoinitiator, aiming to improve membranes’ stability in biological fluids. Moreover, meshes suitability to be used as vascular grafts was evaluated by characterizing their chemical/physical properties as well as their haemo and biocompatibility in vitro. The obtained results show that the blended polymeric meshes are biodegradable and those with a higher content of gelatin display a lower water contact angle. Blood compatibility studies showed that the photocrosslinked membranes are haemocompatible, i.e. they display low values of thrombogenicity and do not trigger any haemolytic effect. Also, Normal Human Dermal Fibroblasts cells were incubated in the presence of the produced membranes and they were able to adhere and proliferate, thus revealing the biocompatibility of the photocrosslinked meshes.

Photocrosslinkable surgical adhesives provide many advantages when compared with traditional methods used in wound closure. This work aimed to develop UV-curable biodegradable adhesives based on lactic acid and PCL oligomers. Both materials were functionalized with 2-isocyanatoethyl acrylate (AOI). Subsequently, the photoinitiator (Irgacure® 2959) was added to the blend and then, the final materials were irradiated under UV light for two different times: 30 s and 2 min. After production of adhesives, its physicochemical properties were evaluated through FTIR-ATR and TGA, as well as its rheology, dynamic water contact angle, swelling capacity and hydrolytic degradation. Furthermore, the biocompatibility of the produced adhesives was also characterized in contact with human dermal fibroblasts cells. The antimicrobial activity of the materials was assessed by using Staphylococcus aureus and Escherichia coli, as bacterial models.

The synthesis, functionalization and characterization of low molecular weight L-lactic acid based oligomers to be used as new UV-curable bioadhesives are presented herein. Prepolymers hydroxyl terminated were produced by L-lactic acid dehydration with 1,4-butanediol. The prepolymer was further modified with photoreactive sites by adding an isocyanate-functional unsaturated acrylic ester, which was used for the first time in the biomedical field (LAROMER® LR 9000). Films were afterwards produced upon UV irradiation for 120 s, using a biocompatible photoinitiator (Irgacure® 2959), and finally characterized. The synthesized films exhibited a moderate swelling ratio, suitable for the envisioned application. DSC analysis confirmed an increase in Tg values after each synthesis step. Nevertheless, the film Tg remains lower than the physiological and room temperature. TGA confirmed an improved stability of films at high temperatures. The in vitro degradation tests showed their susceptibility to hydrolysis at 37 °C, suitable for short-term uses. Preliminary evaluation of the adhesion capacity suggested that the synthesized material may be effective in sustaining wound closure and repair. The surface energy was also measured and its value was lower than the ones from blood or skin which supports the previous statement. Blood compatibility studies, cell viability assays (using human dermal fibroblasts) and bacterial inhibition tests (using two bacteria models) were performed. The results indicated that cured adhesive is bio/haemocompatible and possesses antimicrobial activity. Altogether, characterization results showed that the produced material presented a set of properties suitable for biomedical applications, particularly as a surgical adhesive.

Surgeons around the world face the challenge of effectively and securely treat acute wounds. The most used techniques used to reestablish proper tissue continuity and promote healing comprise surgical tape strips and wound suturing or stapling. However, these have different limitations associated, like additional tissue trauma and patient discomfort. Tissue adhesives have emerged as a promising alternative to traditional wound dressings and have been widely explored for their potential to minimize these drawbacks while improving overall outcomes. This study focused on the preparation of photocrosslinkable biomaterials, synthesized from polyethylene glycol (PEG) functionalized with 2-isocyanatoethyl acrylate (AOI), for potential use as tissue adhesives. The synthesized polymers were then crosslinked using two different UV irradiation times (30 and 120 s) to assess how the crosslinking period impacts the final properties of the films. The materials’ chemical composition and thermal and mechanical behavior were further characterized. Rheologic profile, gel content, hydrolytic degradation, and contact angles were assessed. In addition, cytocompatibility evaluation was also conducted. Overall, the obtained data suggest that the newly synthesized tissue adhesives form flexible, homogeneous, and transparent matrices, exhibiting promising properties for potential tissue adhesive applications.

Over the past decade, 3D printing has gained increasing popularity, being a technique capable of producing well-defined tissue-like structures. One of its most appealing features is the ability to create personalized therapies to meet the specific demands of individual patients. However, challenges including the selection of materials, as well as crosslinking strategies still need to be addressed, in order to enhance the inks characteristics and simultaneously create printable, robust, and cytocompatible biomaterials. Hence, this study reports the development of natural-based photoclickable inks, composed of hyaluronic acid (HA) and proteins [bovine serum albumin (BSA) and human platelet lysates (hPL)] for 3D extrusion printing, taking advantage of the versatility, efficiency, and fast kinetics of thiol-ene click chemistry. To this end, HA was modified with norbornene (HA-Nor) moieties, while proteins were thiolated (BSA-SH and hPL-SH). 1H-NMR and ATR-FTIR analysis of the resulting polymers, HA-Nor, BSA-SH and hPL-SH, confirmed the success of their modification. These polymers were mixed, varying the protein concentration and, subsequently, bio-orthogonally photo-crosslinked, using visible light and LAP as photoiniator, creating hydrogel cell-friendly networks. Rheological characterization affirmed the chemistry’s potential in rapidly gelling networks (t < 20 s) achieving an elastic modulus, G’, of approximately 104 Pa, highlighting its suitability for 3D printing applications. Moreover, the mechanical characterization of the hydrogels revealed that those containing higher BSA-SH concentration were more robust, indicating the presence of more crosslinking points, as expected. The mechanical and rheological properties of the inks enabled 3D extrusion printing. Additionally, direct and indirect contact of hASCs with the materials through seeding, confirmed their cytocompatibility and non-toxicity, maintaining cell viability up to 14 days, which was assessed through fluorescence microscopy images and metabolic activity. Therefore, HA-Nor/BSA-SH and HA-Nor/hPL-SH inks are expected to be promising future bioinks for regenerative medicine and tissue engineering of soft tissues, opening avenues for personalized medicine.

So far, the fabrication of man-made living human tissues using bioengineering techniques has remained elusive. Current efforts in the tissue engineering field have been moving towards the fabrication and exploitation of living materials – i.e., cell-rich platforms in which cell-cell interactions govern the material behavior and evolvability. These man-made living architectures aim to present tissue-relevant biofunctionalities and improved bioactivity, revealing tremendous potential for revolutionizing the fields of tissue engineering and disease modeling. To fulfill the pursuit of generating increasingly complex living materials that better mimic native tissues, bioengineering approaches have been focused on exploring the modification of mammalian cell surfaces to attain control over cellular interactions and to promote the assembly of living materials in a unit-programmable manner. Such increment in cellular elements' processability may open new possibilities for promoting the rapid assembly of functionalized cells into multicellular higher-order architectures in time-frames that are compatible with cell processing technologies, such as biofabrication, allowing the generation of living structures capable of closely resembling the architectural complexity and biological performance of native tissues. To be a step closer to this goal, herein, metabolic glycoengineering coupled with photo-chemistry was used to increase the versatility and processing speed of mammalian cells into 3D living materials as this has remained unattainable so far. The developed methodology led to the manufacture of mammalian living materials with suitable stability and cell viability for 7 days in culture. In the near future, these findings open new avenues to explore the light-based manufacturing of living constructs using advanced biofabrication technologies.