Bone tissue engineering has emerged as a promising strategy to overcome the limitations of current treatments for bone-related disorders, but the trade-off between mechanical properties and bioactivity remains a concern for many polymeric materials. To address this need, novel polymeric blends of poly-L-lactic acid (PLLA), polycaprolactone (PCL) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) have been explored. Blend filaments comprising PLLA/PCL/PHBV at a ratio of 90/5/5 wt% have been prepared using twin-screw extrusion. The PLLA/PCL/PHBV blends were enriched with nano-hydroxyapatite (nano-HA) and strontium-substituted nano-HA (Sr-nano-HA) to produce composite filaments. Three-dimensional scaffolds were printed by fused deposition modelling from PLLA/PCL/PHBV blend and composite filaments and evaluated mechanically and biologically for their capacity to support bone formation in vitro. The composite scaffolds had a mean porosity of 40%, mean pores of 800 µm, and an average compressive modulus of 32 MPa. Polymer blend and enriched scaffolds supported cell attachment and proliferation. The alkaline phosphatase activity and calcium production were significantly higher in composite scaffolds compared to the blends. These findings demonstrate that thermoplastic polyesters (PLLA and PCL) can be combined with polymers produced via a bacterial route (PHBV) to produce polymer blends with excellent biocompatibility, providing additional options for polymer blend optimization. The enrichment of the blend with nano-HA and Sr-nano-HA powders enhanced the osteogenic potential in vitro.
A major challenge for future drug development comprises finding alternative models for drug screening. The use of animal models in research is highly controversial, with an ongoing debate on their ethical acceptability. Also, animal models are often poorly predictive of therapeutic outcomes due to the differences between animal and human physiological environments. In this study, we aimed to develop a biomimetic hydrogel that replicates the composition of skin for potential use in in vitro modeling within tissue engineering. The hydrogel was fabricated through the crosslinking of collagen type I, hyaluronic acid, four-arm PEG succinimidyl glutarate (4S-StarPEG), and fibrinogen. Various ratios of these components were systematically optimized to achieve a well-interconnected porosity and desirable rheological properties. To evaluate the hydrogel’s cytocompatibility, fibroblasts were embedded within the matrix. The resulting hydrogel exhibited promising properties as a scaffold, also facilitating the growth of and proliferation of the cells. This biomimetic hydrogel holds great potential for tissue engineering applications, particularly in skin regeneration and cancer research. The study used melanoma spheroids fabricated using the 96-round bottom well plate method as a potential application. The results demonstrate that the developed hydrogels allowed the maintenance of spheroid integrity and viability, meaning it has a promising use as a three-dimensional in vitro model of melanoma for both tissue engineering and drug screening applications.
The treatment of osteoporotic fractures is a severe clinical issue, especially in cases where low support is provided, e.g., pelvis. New treatments aim to stimulate bone formation in compromised scenarios by using multifunctional biomaterials combined with biofabrication techniques to produce 3D structures (scaffolds) that can support bone formation. Bone’s extracellular matrix (ECM) is mainly composed of type I collagen, making this material highly desirable in bone tissue engineering applications, and its bioactivity can be improved by incorporating specific biomolecules. In this work, type I collagen membranes were produced by electrospinning showing a fibre diameter below 200 nm. An optimized one-step strategy allowed to simultaneously crosslink the electrospun membranes and bind ICOS-Fc, a biomolecule able to reversibly inhibit osteoclast activity. The post-treatment did not alter the ECM-like nanostructure of the meshes and the physicochemical properties of collagen. UV-Vis and TGA analyses confirmed both crosslinking and grafting of ICOS-Fc onto the collagen fibres. The preservation of the biological activity of grafted ICOS-Fc was evidenced by the ability to affect the migratory activity of ICOSL-positive cells. The combination of ICOS-Fc with electrospun collagen represents a promising strategy to design multifunctional devices able to boost bone regeneration in osteoporotic fractures.