In bone regeneration, combining natural polymer-based scaffolds with Bioactive Glasses (BGs) is an attractive strategy to improve the mechanical properties of the structure, as well as its bioactivity and regenerative potential. Methods: For this purpose, a well-studied alginate/hydroxyapatite (Alg/HAp) porous scaffold was enhanced with an experimental bioglass (BGMS10), characterized by a high crystallization temperature and containing therapeutic ions such as strontium and magnesium. This resulted in an improved biological response compared to 45S5 Bioglass^®, the “gold” standard among BGs. Porous composite scaffolds were fabricated by freeze-drying technique and characterized by scanning electron microscopy and microanalysis, infrared spectroscopy, and microcomputed tomography. The mechanical properties and cytocompatibility of the new scaffold composition were also evaluated. The addition of bioglass to the Alg/HAp network resulted in a slightly lower porosity. However, despite the change in pore size, the MG-63 cells were able to better adhere and proliferate when cultured for one week on a BG scaffold compared to the control Alg/HAp scaffolds. Thus, our findings indicate that the combination of bioactive glass BGMS10 does not affect the structural and physicochemical properties of the Alg/HAp scaffold and confers bioactive properties to the structures, making the Alg/HAp-BGMS10 scaffold a promising candidate for future application in bone tissue regeneration.

The optimized proline-rich antimicrobial peptide B7-005 was loaded on bone scaffolds based on polysaccharides and hydroxyapatite. Alginate was firstly chosen in order to exploit its negative charges, which allowed an efficient B7-005 loading but hindered its release, due to the strong interactions with the positive charged peptide. Hence, alginate was substituted with agarose which allowed to prepare scaffolds with similar structure, porosity, and mechanical performance than the ones prepared with alginate and hydroxyapatite. Moreover, agarose scaffolds could release B7-005 within the first 24 h of immersion in aqueous environment. The peptide did not impaired MG-63 cell adhesion and proliferation in the scaffold, and a positive cell proliferation trend was observed up to two weeks. The released B7-005 was effective against the pathogens E. coli, K. pneumoniae, and A. baumannii, but not against S. aureus and P. aeruginosa, thus requiring further tuning of the system to improve its antimicrobial activity.

Bone defects are a global health concern; bone tissue engineering (BTE) is the most promising alternative to reduce patient morbidity and overcome the inherent drawbacks of autograft and allograft bone. Three-dimensional scaffolds are pivotal in this field due to their potential to provide structural support and mimic the natural bone microenvironment. Following an already published protocol, a 3D porous structure consisting of alginate and hydroxyapatite was prepared after a gelation step and a freezing-drying step. Despite the frequent use of alginate in tissue regeneration, the biological inertness of this polysaccharide hampers proper cell colonization and proliferation. Therefore, the purpose of this work was to enhance the biological properties by promoting the interaction and adhesion between cells and biomaterial with the use of Fibronectin. This extracellular matrix protein was physically adsorbed on the scaffold, and its presence was evaluated with environmental scanning electron microscopy (eSEM) and the Micro-Bicinchoninic Acid (μBCA) protein assay. The MG-63 cell line was used for both static and dynamic (i.e., in bioreactor) 3D cell culturing on the scaffolds. The use of the bioreactor allowed for a better exchange of nutrients and oxygen and a better removal of cell catabolites from the inner portion of the construct, mimicking the physiological environment. The functionalized scaffolds showed an improvement in cell proliferation and colonization compared to non-functionalized ones; the effect of the addition of Fibronectin was more evident in the dynamic culturing conditions, where the cells clearly adhered on the surface of functionalized scaffolds.

Driven by the dictates of sustainability, we have designed, realized, and optimized a method for easy development of biocompatible, highly porous, and electrically conductive 3D structures from the combination of natural and synthetic polymers for pressure sensing applications. In particular, a foaming method followed by a fast freezing step, both performed on blends made of silk fibroin (SF) aqueous solution, PEDOT:PSS electrically conductive polymer, and water-soluble PVA, has allowed the fabrication of conductive electrosponges, intrinsically integrating the structural and electrical counterparts of a resistive pressure sensor in a single "green" material. An exhaustive analysis of their structural (with FTIR), morphological (with μ-CT), and mechanical (by means of stress-strain measurements) properties has been performed, of which the latter was coupled with the electrical characterization of the electrosponges while undergoing compression-decompression cycles. PVA addition has been recognized as crucial for conferring to the material the right compromise among elasticity, recovery attitude, and resilience/durability to the proposed constructs. The fabricated electrosponges show a promising combination of mechanical and electrical properties, with the former induced by both the highly porous structure of the foamed/frozen compound and the elasticity enhancement induced by PVA, whose concentration influences the electrosponge resilience and recovery attitude. Based on the results from the material characterization, the composite with 1% v/v PVA content has shown the best compromise among elasticity, resilience, and shape recovery. The related sensor shows a sensitivity comparable to other hybrid SF composites (10^-3 kPa/mA vs 10^-3-10^-2 kPa/decade), an applied stress magnitude-dependent swiftness (from hundreds of milliseconds to few seconds), and an exhaustive current recovery on numerous repeated compression-decompression cycles in wet conditions.

Alginate-hydroxyapatite (AL) scaffolds modified with fibronectin (FN) or bioactive glass (BGMS10) have recently been characterized for their physicochemical properties and proposed as promising candidates for bone regeneration. Here, we present their first systematic biological evaluation, focusing on adhesion, proliferation, osteogenic differentiation, and in vivo host response. We compared FN-, BG-, and unmodified AL scaffolds using an immortalized mesenchymal stromal cell line (M-SOD) and primary human bone marrow-derived (BM-MSCs) and adipose-derived stromal cells (ASCs). FN scaffolds enhanced initial adhesion across all cell types and supported proliferation in M-SODs, but primary BM-MSCs and ASCs showed minimal expansion, regardless of scaffold type. BG scaffolds promoted expression of late-stage osteogenic markers in BM-MSCs, consistent with their ion release profile, but had limited impact on ASCs. In vivo subcutaneous implantation of acellular scaffolds in nude mice revealed robust host cell infiltration and extracellular matrix deposition across all scaffold types, confirming biocompatibility and integration. However, vascularization remained limited and did not differ substantially between formulations. Together, these findings highlight a critical discrepancy between immortalized and primary stromal cell responses to scaffold cues, underscoring the choice of cell source when evaluating the biocompatibility of a novel scaffold. At the same time, the effective in vivo integration observed across scaffold types emphasizes the importance of host tissue responses for translational evaluation of functional biomaterials.