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Recently, the term theragenerative has been proposed for biomaterials capable of inducing therapeutic approaches followed by repairing/regenerating the tissue/organ. This study is focused on the design of a new theragenerative nanocomposite composed of an amphiphilic non-ionic surfactant (Pluronic F127), bioactive glass (BG), and black phosphorus (BP). The nanocomposite was prepared through a two-step synthetic strategy, including a microwave treatment that turned BP nanosheets (BPNS) into quantum dots (BPQDs) with 5 ± 2 nm dimensions in situ. The effects of surfactant and microwave treatment were assessed in vitro: the surfactant distributes the ions homogenously throughout the composite and the microwave treatment chemically stabilizes the composite. The presence of BP enhanced bioactivity and promoted calcium phosphate formation in simulated body fluid. The inherent anticancer activity of BP-containing nanocomposites was tested against osteosarcoma cells in vitro, finding that 150 μg mL−1 was the lowest concentration which prevented the proliferation of SAOS-2 cells, while the counterpart without BP did not affect the cell growth rate. Moreover, the apoptosis pathways were evaluated and a mechanism of action was proposed. NIR irradiation was applied to induce further proliferation suppression on SAOS-2 cells through hyperthermia. The inhibitory effects of bare BP nanomaterials and nanocomposites on the migration and invasion of bone cancer, breast cancer, and prostate cancer cells were assessed in vitro to determine the anticancer potential of nanomaterials against primary and secondary bone cancers. The regenerative behavior of the nanocomposites was tested with healthy osteoblasts and human mesenchymal stem cells; the BPQDs-incorporated nanocomposite significantly promoted the proliferation of osteoblast cells and induced the osteogenic differentiation of stem cells. This study introduces a new multifunctional theragenerative platform with promising potential for simultaneous bone cancer therapy and regeneration.

Abstract Supramolecular peptides exhibit obvious similarities with collagen fibers in terms of self-assembly characteristics, nanofibrous structure, and responsiveness to external stimuli. Here, a series of supramolecular peptides were developed by altering the amino acid sequence, enabling the self-assembly of three types of 4-biphenylacetic acid (BPAA)-tripeptides into fibrous hydrogel through hydrogen bonding and π–π stacking under the influence of ion induction. Transmission electron and scanning electron microscopies revealed that the diameter of the fiber within nanofibrous hydrogels was ~ 10 and ~ 40 nm, respectively, which was similar with the self-assembled collagen fibers. For this reason, these hydrogels could be considered as a biomimetic extracellular substitute. Meanwhile, the gelation concentration induced by ions was even lower than 0.66 wt%, with an elastic modulus of ~ 0.27 kPa, corresponding to a water content of 99.34 wt%. In addition, the three supramolecular hydrogels were found to be good substrates for L929 cell adhesion and MC-3T3 cell proliferation. The overall results implied that BPAA-based hydrogels have a lucrative application potential as cell carriers. Graphical Abstract

Abstract During the development of the nervous system, neurons sense and respond to topographical and biochemical cues found in the brain's native environment. Such niche‐specific cues are pivotal for neural tissue formation and development and have been now widely exploited in neural tissue engineering to develop biologically‐inspired scaffolds able to trigger a desired neuronal behavior. In particular, anisotropic aligned fibers, recapitulating the design of extending axonal tracts or aligned fibers found in the extracellular environment, have emerged as ideal candidates to guide cell alignment and elongation along the substrate main axis as well as promote neuronal differentiation. Among natural polymers used for coatings, melanins, including eumelanin, have been shown to possess antioxidant, anti‐inflammatory, immunomodulatory, and photo‐protective properties. Here, aligned poly(lactic acid) (PLA) fibers are fabricated via electrospinning and then coated with eumelanin via spin coating. Eumelanin‐coated aligned PLA fibers are highly biocompatible and greatly influenced the adhesion, morphology, and spreading of SH‐SY5Y neuroblastoma cells. Furthermore, the eumelanin coating is crucial in promoting cell alignment at the cell‐material interface and SH‐SY5Y cell maturation towards a more mature neuronal phenotype.

Abstract Nowadays, prostate cancer is the most widespread tumour in worldwide male population. Actually, brachytherapy is the most advanced radiotherapy strategy for the local treatment of prostate cancer. It consists in the placing of radioactive sources closed to the tumour side thus killing cancer cells. However, brachytherapy causes the same adverse effects of external-beam radiotherapy. Therefore, alternative treatment approaches are required for enhancing radiotherapy effectiveness and reducing toxic symptoms. Nanostructured exfoliated black phosphorus (2D BP) may represent a strategic tool for local cancer therapy because of its capability to induce singlet oxygen production and act as photosensitizer. Hence, we investigated 2D BP in vitro effect on healthy and cancer prostate cell behavior. 2D BP was obtained through liquid exfoliation. 2D BP effect on healthy and cancer prostate cell behaviors was analyzed by investigating cell viability, oxidative stress and inflammatory marker expression. 2D BP inhibited prostate cancer cell survival, meanwhile promoted healthy prostate cell survival in vitro by modulating oxidative stress and immune response with and without near-infrared light (NIR)-irradiation. Nanostructured 2D BP is able to inhibit in vitro prostate cancer cells survival and preserve healthy prostate cell vitality through the control of oxidative stress and immune response, respectively.

The species of Candida present good capability to form fungal biofilms on polymeric surfaces and are related to several human diseases since many of the employed medical devices are designed using polymers, especially high-density polyethylene (HDPE). Herein, HDPE films containing 0; 0.125; 0.250 or 0.500 wt% of 1-hexadecyl-3-methylimidazolium chloride (C16MImCl) or its analog 1-hexadecyl-3-methylimidazolium methanesulfonate (C16MImMeS) were obtained by melt blending and posteriorly mechanically pressurized into films. This approach resulted in more flexible and less brittle films, which impeded the Candida albicans, C. parapsilosis, and C. tropicalis biofilm formation on their surfaces. The employed imidazolium salt (IS) concentrations did not present any significant cytotoxic effect, and the good cell adhesion/proliferation of human mesenchymal stem cells on the HDPE-IS films indicated good biocompatibility. These outcomes combined with the absence of microscopic lesions in pig skin after contact with HDPE-IS films demonstrated their potential as biomaterials for the development of effective medical device tools that reduce the risk of fungal infections.

Gellan gum (GG) was chemically modified with methacrylic moieties to produce a photocrosslinkable biomaterial ink, hereinafter called methacrylated GG (GGMA), with improved physico-chemical properties, mechanical behavior and stability under physiological conditions. Afterwards, GGMA was functionalized by incorporating two different bioactive compounds, a naturally derived eumelanin extracted from the black soldier fly (BSF-Eumel), or hydroxyapatite nanoparticles (HAp), synthesized by the sol–gel method. Different ink formulations based on GGMA (2 and 4% (w/v)), BSF-Eumel, at a selected concentration (0.3125 mg/mL), or HAp (10 and 30% wHAp/wGGMA) were developed and processed by three-dimensional (3D) printing. All the functionalized GGMA-based ink formulations allowed obtaining 3D-printed GGMA-based scaffolds with a well-organized structure. For both bioactive signals, the scaffolds with the highest GGMA concentration (4% (w/v)) and the highest percentage of infill (45%) showed the best performances in terms of morphological and mechanical properties. Indeed, these scaffolds showed a good structural integrity over 28 days. Given the presence of negatively charged groups along the eumelanin backbone, scaffolds consisting of GGMA/BSF-Eumel demonstrated a higher stability. From a mechanical point of view, GGMA/BSF-Eumel scaffolds exhibited values of storage modulus similar to those of GGMA ones, while the inclusion of HAp at 30% (wHAp/wGGMA) led to a storage modulus of 32.5 kPa, 3.5-fold greater than neat GGMA. In vitro studies proved the capability of the bioactivated 3D-printed scaffolds to support 7F2 osteoblast cell growth and differentiation. BSF-Eumel and HAp triggered a different time-dependent physiological response in the osteoblasts. Specifically, while the ink with BSF-Eumel acted as a stimulus towards cell proliferation, reaching the highest value at 14 days, a higher expression of alkaline phosphatase activity was detected for scaffolds consisting of GGMA and HAp. The overall findings demonstrated the possible use of these biomaterial inks for 3D-printed bone tissue-engineered scaffolds.

Abstract The class of imidazolium salts contains effective anticorrosion additives for metal substrates. This study evaluated the potential of 1-carboxymethyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide (HO 2 CC 1 MImNTf 2 ) for application in cultural heritage, exploring it as anticorrosion additive in chitosan-based coatings for the protection of copper-based alloys. Under accelerated corrosion conditions with HCl vapor, the chitosan coating with HO 2 CC 1 MImNTf 2 was less effective than the one with benzotriazole. The coating with a combination of HO 2 CC 1 MImNTf 2 and benzotriazole resulted in the optimal protective efficacy of the bronze surface, and it also maintained high transparency without changing the bronze appearance.

Abstract Cancer is one of the top life‐threatening dangers to the human survival, accounting for over 10 million deaths per year. Bioactive glasses have developed dramatically since their discovery 50 years ago, with applications that include therapeutics as well as diagnostics. A new system within the bioactive glass family, mesoporous bioactive glasses (MBGs), has evolved into a multifunctional platform, thanks to MBGs easy‐to‐functionalize nature and tailorable textural properties—surface area, pore size, and pore volume. Although MBGs have yet to meet their potential in tumor treatment and imaging in practice, recently research has shed light on the distinguished MBGs capabilities as promising theranostic systems for cancer imaging and therapy. This review presents research progress in the field of MBG applications in cancer diagnosis and therapy, including synthesis of MBGs, mechanistic overview of MBGs application in tumor diagnosis and drug monitoring, applications of MBGs in cancer therapy ( particularly, targeted delivery and stimuli‐responsive nanoplatforms), and immunological profile of MBG‐based nanodevices in reference to the development of novel cancer therapeutics.

Graphene oxide (GO) and its reduced form (rGO) have recently attracted a fascinating interest due to their physico-chemical properties, which have opened up new and interesting opportunities in a wide range of biomedical applications, such as wound healing. It is worth noting that GO and rGO may offer a convenient access to its ready dispersion within various polymeric matrices (such as cellulose and its derivative forms), owing to their large surface area, based on a carbon skeleton with many functional groups (i.e., hydroxyl, carboxyl, epoxy bridge, and carbonyl moieties). This results in new synergic properties due to the presence of both components (GO or rGO and polymers), acting at different length-scales. Furthermore, they have shown efficient antimicrobial and angiogenic properties, mostly related to the intracellular formation of reactive oxygen species (ROS), which are advantageous in wound care management. For this reason, GO or rGO integration in cellulose-based matrixes have allowed for designing highly advanced multifunctional hybrid nanocomposites with tailored properties. The current review aims to discuss a potential relationship between structural and physico-chemical properties (i.e., size, edge density, surface chemistry, hydrophilicity) of the nanocomposites with antimicrobials and angiogenic mechanisms that synergically influence the wound healing phenomenon, by paying particular attention to recent findings of GO or rGO/cellulose nanocomposites. Accordingly, after providing a general overview of cellulose and its derivatives, the production methods used for GO and rGO synthesis, the mechanisms that guide antimicrobial and angiogenic processes of tissue repair, as well as the most recent and remarkable outcomes on GO/cellulose scaffolds in wound healing applications, will be presented.

Hybrid bone substitute made up of a 3D printed polyetheretherketone (PEEK) scaffold coated with methacrylated hyaluronic acid (MeHA)-hydroxyapatite (HAp) hydrogel is the objective of the present work. Development and characterization of the scaffold and of the MeHA-HAp after its infiltration and UV photocrosslinking have been followed by analyses of its biological properties using human mesenchymal stem cells (MSCs). Interconnected porous PEEK matrices were produced by fused deposition modeling (FDM) characterized by a reticular pattern with 0°/90° raster orientation and square pores. In parallel, a MeHA-HAp slurry has been synthesized and infiltrated in the PEEK scaffolds. The mechanical properties of the coated and pure PEEK scaffold have been evaluated, showing that the inclusion of MeHA-HAp into the lattice geometry did not significantly change the strength of the PEEK structure with Young’s modulus of 1034.9 ± 126.1 MPa and 1020.0 ± 63.7 MPa for PEEK and PEEK-MeHA-HAp scaffolds, respectively. Human MSCs were seeded on bare and coated scaffolds and cultured for up to 28 days to determine the adhesion, proliferation, migration and osteogenic differentiation. In vitro results showed that the MeHA-HAp coating promotes MSCs adhesion and proliferation and contributes to osteogenic differentiation and extracellular matrix mineralization. This study provides an efficient solution for the development of a scaffold combining the great mechanical performances of PEEK with the bioactive properties of MeHA and HAp, having high potential for translational clinical applications.

Materials that are able to produce free radicals have gained increasing attention for environmental and biomedical purposes. Free radicals, such as the superoxide anion (O2•−), act as secondary messengers in many physiological pathways, such as cell survival. Therefore, the production of free radicals over physiological levels has been exploited in the treatment of different types of cancer, including osteosarcoma (OS). In most cases, the production of reactive oxygen species (ROS) by materials is light-induced and requires the use of chemical photosensitisers, making it difficult and expensive. Here, for the first time, we propose photoluminescent hybrid ZrO2-acetylacetonate nanoparticles (ZrO2-acac NPs) that are capable of generating O2•− without light activation as an adjuvant for the treatment of OS. To increase the uptake and ROS generation in cancer cells, we modify the surface of ZrO2-acac NPs with hyaluronic acid (HA), which recognizes and binds to the surface antigen CD44 overexpressed on OS cells. Since these nanoparticles emit in the visible range, their uptake into cancer cells can be followed by a label-free approach. Overall, we show that the generation of O2•− is toxic to OS cells and can be used as an adjuvant treatment to increase the efficacy of conventional drugs.

An optimized extraction protocol for eumelanins from black soldier flies (BSF-Eumel) allows an in-depth study of natural eumelanin pigments, which are a valuable tool for the design and fabrication of sustainable scaffolds. Here, water-soluble BSF-Eumel sub-micrometer colloidal particles were used as bioactive signals for developing a composite biomaterial ink for scaffold preparation. For this purpose, BSF-Eumel was characterized both chemically and morphologically; moreover, biological studies were carried out to investigate the dose-dependent cell viability and its influence on human mesenchymal stem cells (hMSCs), with the aim of validating suitable protocols and to find an optimal working concentration for eumelanin-based scaffold preparation. As proof of concept, 3D printed scaffolds based on methacrylated hyaluronic acid (MEHA) and BSF-Eumel were successfully produced. The scaffolds with and without BSF-Eumel were characterized in terms of their physico-chemical, mechanical and biological behaviours. The results showed that MEHA/BSF-Eumel scaffolds had similar storage modulus values to MEHA scaffolds. In terms of swelling ratio and stability, these scaffolds were able to retain their structure without significant changes over 21 days. Biological investigations demonstrated the ability of the bioactivated scaffolds to support the adhesion, proliferation and osteogenic differentiation of human mesenchymal stem cells.

Black phosphorus nanosheets (2D BP) are emerging as very promising, highly selective chemotherapeutic agents due to their fast degradation in the intracellular matrix of cancer cells. Here, optical diffraction tomography (ODT) and Raman spectroscopy were exploited as a powerful label-free approach to achieve integrated insights into the processes accompanying the administration of exfoliated 2D BP flakes in human prostatic adenocarcinoma and normal human prostate epithelial cells. Our ODT experiments provided unambiguous visualization of the 2D BP internalization in cancer cells and the morphological modifications of those cells in the apoptotic phase. The cellular internalization and damaging occurred, respectively, 18 h and 36–48 h after the 2D BP administration. Changes in the chemical properties of the internalized 2D BP flakes were monitored by Raman spectroscopy. Interestingly, a fast oxidation process of the 2D BP flakes was activated in the intracellular matrix of the cancer cells after 24 h of incubation. This was in sharp contrast to the low 2D BP uptake and minimal chemical changes observed in the normal cells. Along with the understanding of the 2D BP fate in the cancer cells, the proposed label-free morpho-molecular approach offers a powerful, rapid tool to study the pharmacokinetic properties of engineered nanomaterials in preclinical research.

Magnesium (Mg)- and silicon (Si)-substituted hydroxyapatite (HA) scaffolds were synthesized using the sponge replica method. The influence of Mg2+ and SiO44− ion substitution on the microstructural, mechanical and biological properties of HA scaffolds was evaluated. All synthesized scaffolds exhibited porosity >92%, with interconnected pores and pore sizes ranging between 200 and 800 μm. X-ray diffraction analysis showed that β-TCP was formed in the case of Mg substitution. X-ray fluorescence mapping showed a homogeneous distribution of Mg and Si ions in the respective scaffolds. Compared to the pure HA scaffold, a reduced grain size was observed in the Mg- and Si-substituted scaffolds, which greatly influenced the mechanical properties of the scaffolds. Mechanical tests revealed better performance in HA-Mg (0.44 ± 0.05 MPa), HA-Si (0.64 ± 0.02 MPa) and HA-MgSi (0.53 ± 0.01 MPa) samples compared to pure HA (0.2 ± 0.01 MPa). During biodegradability tests in Tris-HCl, slight weight loss and a substantial reduction in mechanical performances of the scaffolds were observed. Cell proliferation determined by the MTT assay using hBMSC showed that all scaffolds were biocompatible, and the HA-MgSi scaffold seemed the most effective for cell adhesion and proliferation. Furthermore, ALP activity and osteogenic marker expression analysis revealed the ability of HA-Si and HA-MgSi scaffolds to promote osteoblast differentiation.

Cellulose represents a low cost, abundant, and renewable polysaccharide with great versatility; it has a hierarchical structure composed of nanofibers with high aspect ratio (3–4 nm wide, hundreds of μm long). TEMPO-mediated oxidation represents one of the most diffused methods to obtain cellulose nanofibers (CNFs): It is possible to obtain physically crosslinked hydrogels by means of divalent cation addition. The presence of inorganic components, such as calcium phosphates (CaP), can improve not only their mechanical properties but also the bioactivity of the gels. The aim of this work is to design and characterize a TEMPO-oxidized cellulose nanofibers (TOCNFs) injectable hydrogel embedded with inorganic particles, CaP and CaP-GO, for bone tissue regeneration. Inorganic particles act as physical crosslinkers, as proven by rheological characterization, which reported an increase in mechanical properties. The average load value registered in injection tests was in the range of 1.5–4.4 N, far below 30 N, considered a reasonable injection force upper limit. Samples were stable for up to 28 days and both CaP and CaP-GO accelerate mineralization as suggested by SEM and XRD analysis. No cytotoxic effects were shown on SAOS-2 cells cultured with eluates. This work demonstrated that the physicochemical properties of TOCNFs-based dispersions could be enhanced and modulated through the addition of the inorganic phases, maintaining the injectability and bioactivity of the hydrogels.

Bone cancer is a demanding challenge for contemporary medicine due to its high frequency of presentation and significant heterogeneity of malignant lesions developing within the bone. To date, available treatments are rarely curative and are primarily aimed at prolonging patients’ survival and ameliorating their quality of life. Furthermore, both pharmacological and surgical therapies are aggravated by a consistent burden of adverse events and subsequent disability due to the loss of healthy bone structural and functional properties. Therefore, great research efforts are being made to develop innovative biomaterials able to selectively inhibit bone cancer progression while reducing the loss of bone structural properties secondary to local tissue invasion. In this review, we describe the state of the art of innovative biomaterials for the treatment of bone cancer. Along with physiological bone remodeling, the development of bone metastasis and osteosarcoma will be depicted. Subsequently, recent advances on nanocarrier-based drug delivery systems, as well as the application of novel, multifunctional biomaterials for the treatment of bone cancer will be discussed. Eventually, actual limitations and promising future perspectives regarding the employment of such approaches in the clinical scenario will be debated.

Over the years, there has been an increasing number of cardiac and orthopaedic implanted medical devices, which has caused an increased incidence of device-associated infections. The surfaces of these indwelling devices are preferred sites for the development of biofilms that are potentially lethal for patients. Device-related infections form a large proportion of hospital-acquired infections and have a bearing on both morbidity and mortality. Treatment of these infections is limited to the use of systemic antibiotics with invasive revision surgeries, which had implications on healthcare burdens. The purpose of this review is to describe the main causes that lead to the onset of infection, highlighting both the biological and clinical pathophysiology. Both passive and active surface treatments have been used in the field of biomaterials to reduce the impact of these infections. This includes the use of antimicrobial peptides and ionic liquids in the preventive treatment of antibiotic-resistant biofilms. Thus far, multiple in vivo studies have shown efficacious effects against the antibiotic-resistant biofilm. However, this has yet to materialize in clinical medicine.

The present work is focused on the development of gelatin-based scaffolds crosslinked through carbodiimide reaction and their bioactivation by two different methods: (i) surface modification by inorganic signals represented by hydroxyapatite nanoparticles precipitated on scaffold through biomimetic treatment; (ii) analog of BMP-2 peptide decoration. The results showed the effects of polymer concentration and crosslinking time on the physico-chemical, morphological, and mechanical properties of scaffolds. Furthermore, a comparative study of biological response for both bioactivated structures allowed to evaluate the influence of inorganic and organic cues on cellular behavior in terms of adhesion, proliferation and early osteogenic marker expression. The bioactivation by inorganic cues induced positive cellular response compared to neat scaffolds in terms of increased cell proliferation and early osteogenic differentiation of human mesenchymal stem cell (hMSC), as evidenced by the Alkaline phosphatase (ALP) expression. Similarly BMP-2 peptide decorated scaffolds showed higher values of ALP than biomineralized ones at longer time. The overall results demonstrated that the presence of bioactive signals (either inorganic or organic) at nanoscale level allowed an osteoinductive effect on hMSC in a basal medium, making the modified gelatin scaffolds a promising candidate for bone tissue regeneration.

In this study, free-standing expanded graphite chitosan (EG-chitosan) nanocomposite films have been prepared using a novel green and simple preparation method, starting from a commercial expandable graphite (GIC). The in situ exfoliation of GIC by a solvent-free sonication method was monitored as a function of the process parameters using X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS) and UV-visible transmittance (UV-VIS) analyses. The optimal process parameters were selected in order to obtain an efficient dispersion of EG in chitosan solutions. The effective EG amount after the in situ exfoliation was also determined by thermogravimetric analyses.

Bone fractures related to musculoskeletal disorders determine long-term disability in older people with a consequent significant economic burden. The recovery of pathologically impaired tissue architecture allows avoiding bone loss-derived consequences such as bone height reduction, deterioration of bone structure, inflamed bone pain, and high mortality for thighbone fractures. Actually, standard therapy for osteoporosis treatment is based on the systemic administration of biphosphonates and anti-inflammatory drugs, which entail several side effects including gastrointestinal (GI) diseases, fever, and articular pain. Hence, the demand of innovative therapeutic approaches for locally treating bone lesions has been increasing in the last few years. In this scenario, the development of injectable materials loaded with therapeutically active agents (i.e., anti-inflammatory drugs, antibiotics, and peptides mimicking growth factors) could be an effective tool to treat bone loss and inflammation related to musculoskeletal diseases, including osteoporosis and osteoarthritis. According to this challenge, here, we propose three different compositions of injectable calcium phosphates (CaP) as new carrier materials of therapeutic compounds such as bisphosphonates (i.e., alendronate), anti-inflammatory drugs (i.e., diclofenac sodium), and natural molecules (i.e., harpagoside) for the local bone disease treatment. Biological quantitative analyses were performed for screening osteoinductive and anti-inflammatory properties of injectable drug-loaded systems. Meanwhile, cell morphological features were analyzed through scanning electron microscopy and confocal investigations. The results exhibited that the three systems exerted an osteoinductive effect during later phases of osteogenesis. Simultaneously, all compositions showed an anti-inflammatory activity on inflammation in vitro models.

Ti6Al4V alloy is still attracting great interest because of its application as an implant material for hard tissue repair. This research aims to produce and investigate in-situ chitosan/hydroxyapatite (CS/HA) nanocomposite coatings based on different amounts of HA (10, 50 and 60 wt.%) on alkali-treated Ti6Al4V substrate through the sol-gel process to enhance in vitro bioactivity. The influence of different contents of HA on the morphology, contact angle, roughness, adhesion strength, and in vitro bioactivity of the CS/HA coatings was studied. Results confirmed that, with increasing the HA content, the surface morphology of crack-free CS/HA coatings changed for nucleation modification and HA nanocrystals growth, and consequently, the surface roughness of the coatings increased. Furthermore, the bioactivity of the CS/HA nanocomposite coatings enhanced bone-like apatite layer formation on the material surface with increasing HA content. Moreover, CS/HA nanocomposite coatings were biocompatible and, in particular, CS/10 wt.% HA composition significantly promoted human mesenchymal stem cells (hMSCs) proliferation. In particular, these results demonstrate that the treatment strategy used during the bioprocess was able to improve in vitro properties enough to meet the clinical performance. Indeed, it is predicted that the dense and crack-free CS/HA nanocomposite coatings suggest good potential application as dental implants.

Genipin (GN) is a natural molecule extracted from the fruit of Gardenia jasminoides Ellis according to modern microbiological processes. Genipin is considered as a favorable cross-linking agent due to its low cytotoxicity compared to widely used cross-linkers; it cross-links compounds with primary amine groups such as proteins, collagen, and chitosan. Chitosan is a biocompatible polymer that is currently studied in bone tissue engineering for its capacity to promote growth and mineral-rich matrix deposition by osteoblasts in culture. In this work, two genipin cross-linked chitosan scaffolds for bone repair and regeneration were prepared with different GN concentrations, and their chemical, physical, and biological properties were explored. Scanning electron microscopy and mechanical tests revealed that nonremarkable changes in morphology, porosity, and mechanical strength of scaffolds are induced by increasing the cross-linking degree. Also, the degradation rate was shown to decrease while increasing the cross-linking degree, with the high cross-linking density of the scaffold disabling the hydrolysis activity. Finally, basic biocompatibility was investigated in vitro, by evaluating proliferation of two human-derived cell lines, namely, the MG63 (human immortalized osteosarcoma) and the hMSCs (human mesenchymal stem cells), as suitable cell models for bone tissue engineering applications of biomaterials.

In this study, an innovative polymer blend, based on double network (DN) approach, has been developed by integrating a poly(ethylene glycol) diacrylate (PEGDA) network into a chemically modified hyaluronic acid sodium salt (HAs) hydrogel matrix. Here, the HAs was chemically functionalized with photocrosslinkable moieties by reacting with maleic anhydride (MAA) to obtain a maleated hyaluronic acid (MaHA). Furthermore, nanocomposite DN hydrogels were suitably prepared by physical blending of hydroxyapatite nanoparticles (HAp), obtained by sol-gel synthesis, within the hydrogel. Physico-chemical, thermal, morphological and mechanical analyses were performed. Results showed enhanced mechanical properties and a homogenous microstructure as highlighted by mechanical and morphological investigations. This suggests that nanocomposite DN hydrogels are promising candidates for biomedical applications.

Hydrogels currently represent a powerful solution to promote the regeneration of soft and hard tissues. Primarily, they assure efficient bio-molecular interactions with cells, also regulating their basic functions, guiding the spatially and temporally complex multi-cellular processes of tissue formation, and ultimately facilitating the restoration of structure and function of damaged or dysfunctional tissues. In order to overcome basic drawbacks of traditional synthesized hydrogels, many recent strategies have been implemented to realize multi-component hydrogels based on natural and/or synthetic materials with tailored chemistries and different degradation kinetics. Here, a critical review of main strategies has been proposed based on the use of hydrogels-based devices for the regeneration of complex tissues, i.e., osteo-chondral tissues and intervertebral disc.