Editor’s Choice Articles

Biopolymers formed into a fibrous morphology through electrospinning are of increasing interest in the field of biomedicine due to their intrinsic biocompatibility and biodegradability and their ability to be biomimetic to various fibrous structures present in animal tissues. However, their mechanical properties are often unsatisfactory and their processing may be troublesome. Thus, extensive research interest is focused on improving these qualities. This review article presents the selection of the recent advances in techniques aimed to improve the electrospinnability of various biopolymers (polysaccharides, polynucleotides, peptides, and phospholipids). The electrospinning of single materials, and the variety of co-polymers, with and without additives, is covered. Additionally, various crosslinking strategies are presented. Examples of cytocompatibility, biocompatibility, and antimicrobial properties are analyzed. Special attention is given to whey protein isolate as an example of a novel, promising, green material with good potential in the field of biomedicine. This review ends with a brief summary and outlook for the biomedical applicability of electrospinnable biopolymers. Full article

Human adipose stem cells (hASCs) are promising candidates for cell-based therapies, but they need to be efficiently expanded in vitro as they cannot be harvested in sufficient quantities. Recently, dynamic bioreactor systems operated with microcarriers achieved considerable high cell densities. Thus, they are a viable alternative to static planar cultivation systems to obtain high numbers of clinical-grade hASCs. Nevertheless, the production of considerable biomass in a short time must not be achieved to the detriment of the cells’ quality. To facilitate the scalable expansion of hASC, we have developed a new serum- and xeno-free medium (UrSuppe) and a biodegradable microcarrier (BR44). In this study, we investigated whether the culture of hASCs in defined serum-free conditions on microcarriers (3D) or on planar (2D) cell culture vessels may influence the expression of some marker genes linked with the immature degree or the differentiated status of the cells. Furthermore, we investigated whether the biomaterials, which form our biodegradable MCs, may affect cell behavior and differentiation. The results confirmed that the quality and the undifferentiated status of the hASCs are very well preserved when they grow on BR44 MCs in defined serum-free conditions. Indeed, the ASCs showed a gene expression profile more compatible with an undifferentiated status than the same cells grown under standard planar conditions. Full article

The inclusion of biofunctional molecules with synthetic bone graft substitutes has the potential to enhance tissue regeneration during treatment of traumatic bone injuries. The clinical use of growth factors has though been associated with complications, some serious. The use of smaller, active peptides has the potential to overcome these problems and provide a cost-effective, safe route for the manufacture of enhanced bone graft substitutes. This review considers the design of peptide-enhanced bone graft substitutes, and how peptide selection and attachment method determine clinical efficacy. It was determined that covalent attachment may reduce the known risks associated with growth factor-loaded bone graft substitutes, providing a predictable tissue response and greater clinical efficacy. Peptide choice was found to be critical, but even within recognised families of biologically active peptides, the configurations that appeared to most closely mimic the biological molecules involved in natural bone healing processes were most potent. It was concluded that rational, evidence-based design of peptide-enhanced bone graft substitutes offers a pathway to clinical maturity in this highly promising field. Full article

This study involves the synthesis of hydroxyapatite and describes the preparation and characterization of polymer coatings based on poly(ethylene glycol) diacrylate and poly(ethylene glycol) and modified with bovine serum albumin and hydroxyapatite. Hydroxyapatite was obtained by wet chemical synthesis and characterized by X-ray diffraction and FTIR spectroscopy, and its Ca/P molar ratio was determined (1.69 ± 0.08). The ceramic and bovine serum albumin were used in the preparation of composite materials with the polymeric matrix. The chemical composition of coatings was characterized with FTIR spectroscopy, and their morphology was recorded with SEM imaging. Moreover, the measurements of surface roughness parameters and stereometric research were performed. The prepared coatings were subjected to in vitro studies in simulated body fluid and artificial saliva. Changes in chemical composition and morphology after immersion were examined with FTIR spectroscopy and SEM imaging. Based on the conducted research, it can be stated that applied modifiers promote the biomineralization process. The roughness analysis confirmed prepared materials were characterized by the micrometer-scale topography. The materials morphology and roughness, and the morphology of the newly formed apatite deposit, were dependent on the type of the used modifier, and the artificial fluid used in in vitro studies. Full article

In addition to biocompatibility, an ideal scaffold for the regeneration of valvular tissue should also replicate the natural heart valve extracellular matrix (ECM) in terms of biomechanical properties and structural stability. In our previous paper, we demonstrated the development of collagen type I and hyaluronic acid (HA)-based scaffolds with interlaced microstructure. Such hybrid scaffolds were found to be compatible with cardiosphere-derived cells (CDCs) to potentially regenerate the diseased aortic heart valve. This paper focused on the quantification of the effect of crosslinking density on the mechanical properties under dry and wet conditions as well as degradation resistance. Elastic moduli increased with increasing crosslinking densities, in the dry and wet state, for parent networks, whereas those of interlaced scaffolds were higher than either network alone. Compressive and storage moduli ranged from 35 ± 5 to 95 ± 5 kPa and 16 ± 2 kPa to 113 ± 6 kPa, respectively, in the dry state. Storage moduli, in the dry state, matched and exceeded those of human aortic valve leaflets (HAVL). Similarly, degradation resistance increased with increasing the crosslinking densities for collagen-only and HA-only scaffolds. Interlaced scaffolds showed partial degradation in the presence of either collagenase or hyaluronidase as compared to when exposed to both enzymes together. These results agree with our previous findings that interlaced scaffolds were composed of independent collagen and HA networks without crosslinking between them. Thus, collagen/HA interlaced scaffolds have the potential to fill in the niche for designing an ideal tissue engineered heart valve (TEHV). Full article

Due to the extremely high incidence of lesions and diseases in aging population, it is critical to put all efforts into developing a successful implant for osteochondral tissue regeneration. Many of the patients undergoing surgery present osteochondral fissure extending until the subchondral bone (corresponding to a IV grade according to the conventional radiographic classification by Berndt and Harty). Therefore, strategies for functional tissue regeneration should also aim at healing the subchondral bone and joint interface, besides hyaline cartilage. With the ambition of contributing to solving this problem, several research groups have been working intensively on the development of tailored implants that could promote that complex osteochondral regeneration. These implants may be manufactured through a wide variety of processes and use a wide variety of (bio)materials. This review aimed to examine the state of the art regarding the challenges, advantages, and drawbacks of the current strategies for osteochondral regeneration. One of the most promising approaches relies on the principles of additive manufacturing, where technologies are used that allow for the production of complex 3D structures with a high level of control, intended and predefined geometry, size, and interconnected pores, in a reproducible way. However, not all materials are suitable for these processes, and their features should be examined, targeting a successful regeneration. Full article

Skin regeneration requires a three-dimensional (3D) scaffold for cell adhesion, growth and proliferation. A type of the scaffold offering a 3D structure is a nonwoven material produced via a melt-blown technique. Process parameters of this technique can be adapted to improve the cellular response. Polylactic acid (PLA) was used to produce a nonwoven scaffold by a melt-blown technique. The key process parameters, i.e., the head and air temperature, were changed in the range from 180–270 °C to obtain eight different materials (MB1–MB8). The relationships between the process parameters, morphology, porosity, thermal properties and the cellular response were explored in this study. The mean fiber diameters ranged from 3 to 120 µm. The average material roughness values were between 47 and 160 µm, whereas the pore diameters ranged from 5 to 400 µm. The calorimetry thermograms revealed a correlation between the temperature parameters and crystallization. The response of keratinocytes and macrophages exhibited a higher cell viability on thicker fibers. The cell-scaffold interaction was observed via SEM after 7 days. This result proved that the features of melt-blown nonwoven scaffolds depended on the processing parameters, such as head temperature and air temperature. Thanks to examinations, the most suitable scaffolds for skin tissue regeneration were selected. Full article

Introduction: Many studies in stem cell biology have demonstrated that dental pulp stem cells (DPSC) may be highly proliferative and capable of pluripotent differentiation into many different tissue types. Recent advances in stem cell research have outlined methods for directing in vitro or in vivo growth, viability, and proliferation, as well as differentiation of DPSC—although much remains to be discovered. Based upon this information, the primary objective of this study was to understand the functional biomaterials needed to more effectively direct DPSC viability, growth, and proliferation. Methods: Using an approved protocol, previously collected and isolated samples of DPSC from an existing repository were used. Previously established stem cell biomarkers (Sox-2, Oct-4, NANOG) from each isolate were correlated with their proliferation rates or doubling times to categorize them into rapid, intermediate, or slow-dividing multipotent DPSC. Growth factors and other functional dental biomaterials were subsequently tested to evaluate DPSC responses in proliferation, viability, and morphology. Results: Differential responses were observed among DPSC isolates to growth factors, including vascular endothelial growth factor (VEGF) and bone morphogenic protein (BMP-2), and functional biomaterials such as mineralized trioxide aggregates (MTA). The responsiveness of DPSC isolates did not correlate with any single factor but rather with a combination of proliferation rate and biomarker expression. Conclusions: These data strongly suggest that some, but not all, DPSC isolates are capable of a robust and significant in vitro response to differentiation stimuli, although this response is not universal. Although some biomarkers and phenotypes that distinguish and characterize these DPSC isolates may facilitate the ability to predict growth, viability, and differentiation potential, more research is needed to determine the other intrinsic and extrinsic factors that may contribute to and modulate these DPSC responses to these functional biomaterials for biotechnology and bioengineering applications. Full article

The bone remodeling field has shifted focus towards the delineation of products with two main critical attributes: internal architectures capable to promote fast cell colonization and good mechanical performance. In this paper, Luffa-fibers and graphene nanoplatelets were proposed as porogen template and mechanical reinforcing agent, respectively, in view of framing 3D products by a one-stage polymer-free process. The ceramic matrix was prepared through a reproducible technology, developed for the conversion of marble resources into calcium phosphates (CaP) powders. After the graphene incorporation (by mechanical and ultrasonication mixing) into the CaP matrix, and Luffa-fibers addition, the samples were evaluated in both as-admixed and thermally-treated form (compact/porous products) by complementary structural, morphological, and compositional techniques. The results confirmed the benefits of the two agents’ addition upon the compact products’ micro-porosity and the global mechanical features, inferred by compressive strength and elastic modulus determinations. For the porous products, overall optimal results were obtained at a graphene amount of <1 wt.%. Further, no influence of graphene on fibers’ ability to generate at high temperatures internal interconnected-channels-arrays was depicted. Moreover, its incorporation led to a general preservation of structural composition and stability for both the as-admixed and thermally-treated products. The developed CaP-reinforced structures sustain the premises for prospective non- and load-bearing biomedical applications. Full article

Calcium phosphate coatings are able to improve the osseointegration process due to their chemical composition, which is similar to that of bone tissues. In this work, to increase the long-term corrosion resistance and to improve the osseointegration process of commercially pure titanium Grade 4 (CpTi G4), biomimetic amorphous calcium phosphate (ACP) coatings were electrodeposited for the first time from an acetate bath with a pH level of 7.0 and a Ca:P ratio of 1.67. ACP coatings were obtained on CpTi G4 substrate subjected to sandblasting and autoclaving using electrochemically assisted deposition at a potential of −3 V relative to the open circuit potential for 30 min at room temperature. SEM, EDS, 2D roughness profiles, amplitude-sensitive eddy current method, and Kelvin scanning probe were used for the surface characterization of the biomaterial under study. In vitro corrosion resistance tests were conducted for 21 days in artificial saliva using open circuit potential, polarization curves, and electrochemical impedance spectroscopy measurements. The passive-transpassive behavior was revealed for the obtained ACP coatings. The long-term corrosion resistance test showed a deterioration of the protective properties for CpTi G4 uncoated and coated with ACP with immersion time. The mechanism and kinetics of the pitting corrosion on the CpTi G4|TiO₂|ACP coating system are discussed in detail. Full article

While periprosthetic joint infections (PJIs) result in a small percentage of patients following arthroplasties, they are challenging to treat if they spread into bone and soft tissue. Treatment involves delivering antibiotics using poly(methyl methacrylate) (PMMA) bone cement. However, antibiotic release is insufficient for prolonged infections. Previous work demonstrated efficacy of incorporating insoluble cyclodextrin (CD) microparticles into PMMA to improve antibiotic release and allow for post-implantation drug refilling to occur in a tissue-mimicking model. To simulate how antibiotic refilling may be possible in more physiologically relevant models, this work investigated development of bone and muscle refilling models. The bone refilling model involved embedding PMMA-CD into rabbit femur and administering antibiotic via intraosseous infusion. Muscle tissue refilling model involved implanting PMMA-CD beads in bovine muscle tissue and administering antibiotic via tissue injection. Duration of antimicrobial activity of refilled PMMA-CD was evaluated. PMMA-CD composite in bone and muscle tissue models was capable of being refilled with antibiotics and resulted in prolonged antimicrobial activity. PMMA-CD provided sustained and on-demand antimicrobial activity without removal of implant if infection develops. Intraosseous infusion appeared to be a viable technique to enable refilling of PMMA-CD after implantation in bone, reporting for the first time the ability to refill PMMA in bone. Full article

The aim of this study was to quantitatively evaluate alloplastic Temporomandibular Joint (TMJ) Prostheses against other treatment modalities regarding the jaw kinematics. Six patients with Temporomandibular Joint Prostheses, four with mandibular ramus Patient-Specific Implant (PSI) with condylar head preservation, and four after mandibular condylectomy were evaluated by the means of axiography (Cadiax Compact 2), which is the noninvasive three-dimensional study of condylar movements. The patients were also evaluated clinically for the mandibular movements. The study revealed that the significant movement limitations occurred bilaterally in patients fitted with TMJ prosthesis. For the protrusion movement, the vector length of the movement (L) for the TMJ prosthesis was 0.31 vs. 3.01 mm for the PSI (Kruskal–Wallis chi-squared = 9.1667, df = 2, p-value = 0.01022, post hoc Dunn p-value = 0.015) and for the laterotrusion to the operated side, the length of the vector (L) was 0.66 vs. 3.35 mm, respectively. Statistically significant differences between groups were most frequent for the laterotrusion to the unoperated side. The study shows that a further development on TMJ Prostheses geometry and materials is needed. Full article

Acrylic bone cements modified with linoleic acid are a promising low-modulus alternative to traditional high-modulus bone cements. However, several key properties remain unexplored, including the effect of autoclave sterilization and the potential use of low-modulus cements in other applications than vertebral augmentation. In this work, we evaluate the effect of sterilization on the structure and stability of linoleic acid, as well as in the handling properties, glass transition temperature, mechanical properties, and screw augmentation potential of low-modulus cement containing the fatty acid. Neither ¹H NMR nor SFC-MS/MS analysis showed any detectable differences in autoclaved linoleic acid compared to fresh one. The peak polymerization temperature of the low-modulus cement was much lower (28–30 °C) than that of the high-modulus cement (67 °C), whereas the setting time remained comparable (20–25 min). The T_g of the low-modulus cement was lower (75–78 °C) than that of the high-stiffness cement (103 °C). It was shown that sterilization of linoleic acid by autoclaving did not significantly affect the functional properties of low-modulus PMMA bone cement, making the component suitable for sterile production. Ultimately, the low-modulus cement exhibited handling and mechanical properties that more closely match those of osteoporotic vertebral bone with a screw holding capacity of under 2000 N, making it a promising alternative for use in combination with orthopedic hardware in applications where high-stiffness augmentation materials can result in undesired effects. Full article

In the field of rehabilitation and neuroscience, shape memory alloys play a crucial role as lightweight actuators. Devices are exploiting the shape memory effect by transforming heat into mechanical work. In rehabilitation applications, dynamic loading of the respective device occurs, which in turn influences the mechanical consequences of the phase transforming alloy. Hence in this work, dynamic thermomechanical material behavior of temperature-triggered phase transforming NiTi shape memory alloy (SMA) wires with different chemical compositions and geometries was experimentally investigated. Storage modulus and mechanical loss factor of NiTi alloys at different temperatures and loading frequencies were analyzed under force-controlled conditions. Counterintuitive storage modulus- and loss factor-dependent trends regarding the loading frequency dependency of the mechanical properties on the materials’ composition and geometry were, hence, obtained. It was revealed that loss factors showed a pronounced loading frequency dependency, whereas the storage modulus was not affected. It was shown that force-controlled conditions led to a lower storage modulus than expected. Furthermore, it turned out that a simple empirical relation could capture the characteristic temperature dependency of the storage modulus, which is an important input relation for modeling the rehabilitation device behavior under different dynamic and temperature loading conditions, taking directly into account the material behavior of the shape memory alloy. Full article

Tendons are unique forms of connective tissue aiming to transmit the mechanical force of muscle contraction to the bones. Tendon injury may be due to direct trauma or might be secondary to overuse injury and age-related degeneration, leading to inflammation, weakening and subsequent rupture. Current traditional treatment strategies focus on pain relief, reduction of the inflammation and functional restoration. Tendon repair surgery can be performed in people with tendon injuries to restore the tendon’s function, with re-rupture being the main potential complication. Novel therapeutic approaches that address the underlying pathology of the disease is warranted. Scaffolds represent a promising solution to the challenges associated with tendon tissue engineering. The ideal scaffold for tendon tissue engineering needs to exhibit physiologically relevant mechanical properties and to facilitate functional graft integration by promoting the regeneration of the native tissue. Full article

Conducting polymers (CPs) have been at the center of research owing to their metal-like electrochemical properties and polymer-like dispersion nature. CPs and their composites serve as ideal functional materials for diversified biomedical applications like drug delivery, tissue engineering, and diagnostics. There have also been numerous biosensing platforms based on polyaniline (PANI), polypyrrole (PPY), polythiophene (PTP), and their composites. Based on their unique properties and extensive use in biosensing matrices, updated information on novel CPs and their role is appealing. This review focuses on the properties and performance of biosensing matrices based on CPs reported in the last three years. The salient features of CPs like PANI, PPY, PTP, and their composites with nanoparticles, carbon materials, etc. are outlined along with respective examples. A description of mediator conjugated biosensor designs and enzymeless CPs based glucose sensing has also been included. The future research trends with required improvements to improve the analytical performance of CP-biosensing devices have also been addressed. Full article

Being designated to protect other tissues, skin is the first and largest human body organ to be injured and for this reason, it is accredited with a high capacity for self-repairing. However, in the case of profound lesions or large surface loss, the natural wound healing process may be ineffective or insufficient, leading to detrimental and painful conditions that require repair adjuvants and tissue substitutes. In addition to the conventional wound care options, biodegradable polymers, both synthetic and biologic origin, are gaining increased importance for their high biocompatibility, biodegradation, and bioactive properties, such as antimicrobial, immunomodulatory, cell proliferative, and angiogenic. To create a microenvironment suitable for the healing process, a key property is the ability of a polymer to be spun into submicrometric fibers (e.g., via electrospinning), since they mimic the fibrous extracellular matrix and can support neo- tissue growth. A number of biodegradable polymers used in the biomedical sector comply with the definition of bio-based polymers (known also as biopolymers), which are recently being used in other industrial sectors for reducing the material and energy impact on the environment, as they are derived from renewable biological resources. In this review, after a description of the fundamental concepts of wound healing, with emphasis on advanced wound dressings, the recent developments of bio-based natural and synthetic electrospun structures for efficient wound healing applications are highlighted and discussed. This review aims to improve awareness on the use of bio-based polymers in medical devices. Full article

Polyhydroxyalkanoates (PHAs) are a family of bio-based polyesters that have found different biomedical applications. Chitin and lignin, byproducts of fishery and plant biomass, show antimicrobial and anti-inflammatory activity on the nanoscale. Due to their polarities, chitin nanofibril (CN) and nanolignin (NL) can be assembled into micro-complexes, which can be loaded with bioactive factors, such as the glycyrrhetinic acid (GA) and CN-NL/GA (CLA) complexes, and can be used to decorate polymer surfaces. This study aims to develop completely bio-based and bioactive meshes intended for wound healing. Poly(3-hydroxybutyrate)/Poly(3-hydroxyoctanoate-co-3-hydroxydecanoate), P(3HB)/P(3HO-co-3HD) was used to produce films and fiber meshes, to be surface-modified via electrospraying of CN or CLA to reach a uniform distribution. P(3HB)/P(3HO-co-3HD) fibers with desirable size and morphology were successfully prepared and functionalized with CN and CLA using electrospinning and tested in vitro with human keratinocytes. The presence of CN and CLA improved the indirect antimicrobial and anti-inflammatory activity of the electrospun fiber meshes by downregulating the expression of the most important pro-inflammatory cytokines and upregulating human defensin 2 expression. This natural and eco-sustainable mesh is promising in wound healing applications. Full article

Bacterial colonization of implanted biomedical devices is the main cause of healthcare-associated infections, estimated to be 8.8 million per year in Europe. Many infections originate from damaged skin, which lets microorganisms exploit injuries and surgical accesses as passageways to reach the implant site and inner organs. Therefore, an effective treatment of skin damage is highly desirable for the success of many biomaterial-related surgical procedures. Due to gained resistance to antibiotics, new antibacterial treatments are becoming vital to control nosocomial infections arising as surgical and post-surgical complications. Surface coatings can avoid biofouling and bacterial colonization thanks to biomaterial inherent properties (e.g., super hydrophobicity), specifically without using drugs, which may cause bacterial resistance. The focus of this review is to highlight the emerging role of degradable polymeric micro- and nano-structures that show intrinsic antifouling and antimicrobial properties, with a special outlook towards biomedical applications dealing with skin and skin damage. The intrinsic properties owned by the biomaterials encompass three main categories: (1) physical–mechanical, (2) chemical, and (3) electrostatic. Clinical relevance in ear prostheses and breast implants is reported. Collecting and discussing the updated outcomes in this field would help the development of better performing biomaterial-based antimicrobial strategies, which are useful to prevent infections. Full article

Preventing the development of osteomyelitis while enhancing bone regeneration is challenging, with relatively little progress to date in translating promising technologies to the clinic. Nanoscale hydroxyapatite (nHA) has been employed as a bone graft substitute, and recent work has shown that it may be modified with silver to introduce antimicrobial activity against known pathogens. The aim of this study was to incorporate silver-doped nHA into electrospun scaffolds for applications in bone repair. Silver-doped nHA was produced using a modified, rapid mixing, wet precipitation method at 2, 5, 10 mol.% silver. The silver-doped nHA was added at 20 wt.% to a polycaprolactone solution for electrospinning. Bacteria studies demonstrated reduced bacterial presence, with Escherichia coli and Staphylococcus aureus undetectable after 96 h of exposure. Mesenchymal stem cells (MSCs) were used to study both toxicity and osteogenicity of the scaffolds using PrestoBlue^® and alkaline phosphatase (ALP) assays. Innovative silver nHA scaffolds significantly reduced E. coli and S. aureus bacterial populations while maintaining cytocompatibility with mammalian cells and enhancing the differentiation of MSCs into osteoblasts. It was concluded that silver-doped nHA containing scaffolds have the potential to act as an antimicrobial device while supporting bone tissue healing for applications in orthopedic and dental bone surgery. Full article

The ability to control the interactions between functional biomaterials and biological systems is of great importance for tissue engineering and regenerative medicine. However, the underlying mechanisms defining the interplay between biomaterial properties and the human body are complex. Therefore, a key challenge is to design biomaterials that mimic the in vivo microenvironment. Over millions of years, nature has produced a wide variety of biological materials optimised for distinct functions, ranging from the extracellular matrix (ECM) for structural and biochemical support of cells to the holy lotus with special wettability for self-cleaning effects. Many of these systems found in biology possess unique surface properties recognised to regulate cell behaviour. Integration of such natural surface properties in biomaterials can bring about novel cell responses in vitro and provide greater insights into the processes occurring at the cell-biomaterial interface. Using natural surfaces as templates for bioinspired design can stimulate progress in the field of regenerative medicine, tissue engineering and biomaterials science. This literature review aims to combine the state-of-the-art knowledge in natural and nature-inspired surfaces, with an emphasis on material properties known to affect cell behaviour. Full article

Recently, silver (Ag) and copper (Cu) have been incorporated into a titanium (Ti) surface to realize their antibacterial property. This study investigated both the durability of the antibacterial effect and the surface change of the Ag- and Cu-incorporated porous titanium dioxide (TiO₂) layer. Ag- and Cu-incorporated TiO₂ layers were formed by micro-arc oxidation (MAO) treatment using the electrolyte with Ag and Cu ions. Ag- and Cu-incorporated specimens were incubated in saline during a period of 0–28 days. The changes in both the concentrations and chemical states of the Ag and Cu were characterized using X-ray photoelectron spectroscopy (XPS). The durability of the antibacterial effects against Escherichia coli (E. coli) were evaluated by the international organization for standardization (ISO) method. As a result, the Ag- and Cu-incorporated porous TiO₂ layers were formed on a Ti surface by MAO. The chemical state of Ag changed from Ag₂O to metallic Ag, whilst that of Cu did not change by incubation in saline for up to 28 days. Cu existed as a stable Cu₂O compound in the TiO₂ layer during the 28 days of incubation in saline. The concentrations of Ag and Cu were dramatically decreased by incubation for up to 7 days, and remained a slight amount until 28 days. The antibacterial effect of Ag-incorporated specimens diminished, and that of Cu was maintained even after incubation in saline. Our study suggests the importance of the time-transient effects of Ag and Cu on develop their antibacterial effects. Full article

Titanium nitride (TiN) and silicon carbide (SiC) adhesion properties to biofilm and the proliferation of human osteoblasts were studied. Quaternized titanium nitride (QTiN) was produced by converting the surface nitrogen on TiN to a positive charge through a quaternization process to further improve the antibacterial efficiency. The SiC required a nitridation within the plasma chamber of the surface layer before quaternization could be carried out to produce quaternized SiC (QSiC). The antimicrobial activity was evaluated on the reference strains of Porphyromonas gingivalis for 4 h by fluorescence microscopy using a live/dead viability kit. All the coatings exhibited a lower biofilm coverage compared to the uncoated samples (Ti—85.2%; TiN—24.22%; QTiN—11.4%; SiC—9.1%; QSiC—9.74%). Scanning Electron Microscope (SEM) images confirmed the reduction in P. gingivalis bacteria on the SiC and TiN-coated groups. After 24 h of osteoblast cultivation on the samples, the cell adhesion was observed on all the coated and uncoated groups. Fluorescence images demonstrated that the osteoblast cells adhered and proliferated on the surfaces. TiN and SiC coatings can inhibit the attachment of Porphyromonas gingivalis and promote osteoblast adhesion on the titanium used for implants. These coatings may possess the ability to prevent the development of peri-implantitis and stimulate osteointegration. Full article

In the cosmetic sector, natural and sustainable products with a high compatibility with skin, thus conjugating wellness with a green-oriented consumerism, are required by the market. Poly(hydroxyalkanoate) (PHA)/starch blends represent a promising alternative to prepare flexible films as support for innovative beauty masks, wearable after wetting and releasing starch and other selected molecules. Nevertheless, preparing these films by extrusion is difficult due to the high viscosity of the polymer melt at the temperature suitable for processing starch. The preparation of blends including poly(butylene succinate-co-adipate) (PBSA) or poly(butylene adipate-co-terephthalate) (PBAT) was investigated as a strategy to better modulate melt viscosity in view of a possible industrial production of beauty mask films. The release properties of films in water, connected to their morphology, was also investigated by extraction trials, infrared spectroscopy and stereo and electron microscopy. Then, the biocompatibility with cells was assessed by considering both mesenchymal stromal cells and keratinocytes. All the results were discussed considering the morphology of the films. This study evidenced the possibility of modulating thanks to the selection of composition and the materials processing of the properties necessary for producing films with tailored properties and processability for beauty masks. Full article

Nanobiocomposites suitable for preparing skin compatible films by flat die extrusion were prepared by using plasticized poly(lactic acid) (PLA), poly(butylene succinate-co-adipate) (PBSA), and Chitin nanofibrils as functional filler. Chitin nanofibrils (CNs) were dispersed in the blends thanks to the preparation of pre-nanocomposites containing poly(ethylene glycol). Thanks to the use of a melt strength enhancer (Plastistrength) and calcium carbonate, the processability and thermal properties of bionanocomposites films containing CNs could be tuned in a wide range. Moreover, the resultant films were flexible and highly resistant. The addition of CNs in the presence of starch proved not advantageous because of an extensive chain scission resulting in low values of melt viscosity. The films containing CNs or CNs and calcium carbonate resulted biocompatible and enabled the production of cells defensins, acting as indirect anti-microbial. Nevertheless, tests made with Staphylococcus aureus and Enterobacter spp. (Gram positive and negative respectively) by the qualitative agar diffusion test did not show any direct anti-microbial activity of the films. The results are explained considering the morphology of the film and the different mechanisms of direct and indirect anti-microbial action generated by the nanobiocomposite based films. Full article

The present review had the aim of describing the methodologies of synthesis and properties of biobased pullulan, a microbial polysaccharide investigated in the last decade because of its interesting potentialities in several applications. After describing the implications of pullulan in nano-technology, biodegradation, compatibility with body and skin, and sustainability, the current applications of pullulan are described, with the aim of assessing the potentialities of this biopolymer in the biomedical, personal care, and cosmetic sector, especially in applications in contact with skin. Full article

Microparticles (MPs) with controlled morphologies and sizes have been investigated by several researchers due to their importance in pharmaceutical, ceramic, cosmetic, and food industries to just name a few. In particular, the electrospray (ES) technique has been shown to be a viable alternative for the development of single particles with different dimensions, multiple layers, and varied morphologies. In order to adjust these properties, it is necessary to optimize different experimental parameters, such as polymer solvent, voltage, flow rate (FR), type of collectors, and distance between the collector and needle tip, which will all be highlighted in this review. Moreover, the influence and contributions of each of these parameters on the design and fabrication of polymeric MPs are described. In addition, the most common configurations of ES systems for this purpose are discussed, for instance, the main configuration of an ES system with monoaxial, coaxial, triaxial, and multi-capillary delivery. Finally, the main types of collectors employed, types of synthesized MPs and their applications specifically in the pharmaceutical and biomedical fields will be emphasized. To date, ES is a promising and versatile technology with numerous excellent applications in the pharmaceutical and biomaterials field and such MPs generated should be employed for the improved treatment of cancer, healing of bone, and other persistent medical problems. Full article

Apical periodontitis is a biofilm-mediated disease; therefore, an antimicrobial approach is essential to cure or prevent its development. In the quest for efficient strategies to achieve this objective, antimicrobial photodynamic therapy (aPDT) has emerged as an alternative to classical endodontic irrigation solutions and antibiotics. The aim of the present critical review is to summarize the available evidence on photosensitizers (PSs) which has been confirmed in numerous studies from diverse areas combined with several antimicrobial strategies, as well as emerging options in order to optimize their properties and effects that might be translational and useful in the near future in basic endodontic research. Published data notably support the need for continuing the search for an ideal endodontic photosensitizer, that is, one which acts as an excellent antimicrobial agent without causing toxicity to the human host cells or presenting the risk of tooth discoloration. The current literature on experimental studies mainly relies on assessment of mixed disinfection protocols, combining approaches which are already available with aPDT as an adjunct therapy. In this review, several approaches concerning aPDT efficiency are appraised, such as the use of bacteriophages, biopolymers, drug and light delivery systems, efflux pump inhibitors, negative pressure systems, and peptides. The authors also analyzed their combination with other approaches for aPDT improvement, such as sonodynamic therapy. All of the aforementioned techniques have already been tested, and we highlight the biological challenges of each formulation, predicting that the collected information may encourage the development of other effective photoactive materials, in addition to being useful in endodontic basic research. Moreover, special attention is dedicated to studies on detailed conditions, aPDT features with a focus on PS enhancer strategies, and the respective final antimicrobial outcomes. From all the mentioned approaches, the two which are most widely discussed and which show the most promising outcomes for endodontic purposes are drug delivery systems (with strong development in nanoparticles) and PS solubilizers. Full article

Over the past 10 years, stimuli-responsive polymeric biomaterials have emerged as effective systems for the delivery of therapeutics. Persistent with ongoing efforts to minimize adverse effects, stimuli-responsive biomaterials are designed to release in response to either chemical, physical, or biological triggers. The stimuli-responsiveness of smart biomaterials may improve spatiotemporal specificity of release. The material design may be used to tailor smart polymers to release a drug when particular stimuli are present. Smart biomaterials may use internal or external stimuli as triggering mechanisms. Internal stimuli-responsive smart biomaterials include those that respond to specific enzymes or changes in microenvironment pH; external stimuli can consist of electromagnetic, light, or acoustic energy; with some smart biomaterials responding to multiple stimuli. This review looks at current and evolving stimuli-responsive polymeric biomaterials in their proposed applications. Full article

Grafts are required to restore tissue integrity and function. However, current gold standard autografting techniques yield limited harvest, with high rates of complication. In the search for viable substitutes, the number of biomaterials being developed and studied has increased rapidly. To date, low clinical uptake has accompanied inherently high failure rates, with immune rejection a specific and common end result. The objective of this review article was to evaluate published immune assays evaluating biomaterials, and to stress the value that incorporating immune assessment into evaluations carries. Immunogenicity assays have had three areas of focus: cell viability, maturation and activation, with the latter being the focus in the majority of the literature due to its relevance to functional outcomes. With recent studies suggesting poor correlation between current in vitro and in vivo testing of biomaterials, in vitro immune response assays may be more relevant and enhance ability in predicting acceptance prior to in vivo application. Uptake of in vitro immune response assessment will allow for substantial reductions in experimental time and resources, including unnecessary and unethical animal use, with a simultaneous decrease in inappropriate biomaterials reaching clinic. This improvement in bench to bedside safety is paramount to reduce patient harm. Full article

Nanofibrous-based pH sensors have shown promise in a wide range of industrial and medical applications due to their fast response time and good mechanical properties. In the present study, we fabricated pH-sensitive sensors of nanofibrous membranes by electrospinning polyurethane (PU)/poly 2-acrylamido-2-methylpropanesulfonic acid (PAMPS)/graphene oxide (GO) with indicator dyes. The morphology of the electrospun nanofibers was examined using scanning electron microscopy (SEM). The effect of hydrophilic polymer ratio and concentration of GO on the sensing response time was investigated. The sensitivity of the membranes was studied over a wide pH range (1–8) in solution tests, with color change measured by calculating total color difference using UV-vis spectroscopy. The membranes were also subjected to vapor tests at three different pH values (1, 4, 8). SEM results show the successful fabrication of bimodal fiber diameter distributions of PU (mean fiber diameter 519 nm) and PAMPS (mean fiber diameter 78 nm). Sensing response time decreased dramatically with increasing concentrations of PAMPS and GO. The hybrid hydrophobic/hydrophilic/GO nanofibrous membranes are capable of instantly responding to changes in solution pH as well as detecting pH changes in chemical vapor solution in as little as 7 s. Full article

Porous composite scaffold using an alginate and bioactive glass ICIE16M was synthesized by a simple freeze-drying technique. The scaffold was characterized using compression testing, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), X-ray microtomography (XMT) and scanning electron microscopy (SEM). The bioactivity of the scaffold was evaluated by its ability to form apatite on its surface in simulated body fluid (SBF). The data collected showed evidence that the novel material produced had an appropriate pore size for osteoconduction, with an average pore size of 110 µm and maximum pore size of 309 µm. Statistical analysis confirmed that the glass filler significantly (P < 0.05) increased the collapse yield of the scaffolds compared with pure alginate scaffolds. The ICIE16M glass had an amorphous structure, favorable for bioactivity. Full article

A synthetic technique inspired by the biomineralisation process in nacre has been previously reported to be effective in replicating the nanostructural elements of nacre in 2D chitosan hydrogel films. Here we evaluate the applicability of this synthetic biomineralisation technique, herein called the McGrath method, in replicating the flat tabular morphology of calcium carbonate and other nanostructural elements obtained when 2D chitosan hydrogel films were used, on a 3D porous chitosan hydrogel-based scaffold, hence developing 3D chitosan-calcium carbonate composites. Nozzle extrusion-based 3D printing technology was used to develop 3D porous scaffolds using chitosan hydrogel as the printing ink in a custom-designed 3D printer. The rheology of the printing ink and print parameters were optimised in order to fabricate 3D cylindrical structures with a cubic lattice-based internal structure. The effects of various dehydration techniques, including air-drying, critical point-drying and freeze-drying, on the structural integrity of the as-printed scaffolds from the nano to macroscale, were evaluated. The final 3D composite materials were characterised using scanning electron microscopy, X-ray diffraction and energy dispersive X-ray spectroscopy. The study has shown that McGrath method can be used to develop chitosan-calcium carbonate composites wherein the mineral and matrix are in intimate association with each other at the nanoscale. This process can be successfully integrated with 3D printing technology to develop 3D compartmentalised polymer-mineral composites. Full article

3D printing of polymers can now be considered as a common processing technology for the development of biomaterials. These can be constituted out of polymeric abiotic material alone or can be co-printed with living cells. However, the adaptive and shape-morphing characteristics cannot be developed with the rigid, pre-determined structures obtained by 3D printing. In order to produce functional engineered biomaterials, the dynamic properties/characteristics of the living cells must be attained. 4D printing can be envisaged as a route to achieve these goals. This paper intends to give a brief review of the pioneer 4D printing research that has been developed and to present an insight into future research in this field. Full article

Polymer nanoparticles (NPs) represent one of the most innovative non-invasive approaches for drug delivery applications. NPs main objective is to convey the therapeutic molecule be they drugs, proteins, or nucleic acids directly into the target organ or tissue. Many polymers are used for the synthesis of NPs and among the currently most employed materials several biocompatible synthetic polymers, namely polylactic acid (PLA), poly lactic-co-glycolic acid (PLGA), and polyethylene glycol (PEG), can be cited. These molecules are made of simple monomers which are naturally present in the body and therefore easily excreted without being toxic. The present review addresses the different approaches that are most commonly adopted to synthetize biocompatible NPs to date, as well as the experimental strategies designed to load them with therapeutic agents. In fact, drugs may be internalized in the NPs or physically dispersed therein. In this paper the various types of biodegradable polymer NPs will be discussed with emphasis on their applications in drug delivery. Close attention will be devoted to the treatment of cancer, where both active and passive targeting is used to enhance efficacy and reduce systemic toxicity, and to diseases affecting the central nervous system, inasmuch as NPs can be modified to target specific cells or cross membrane barriers. Full article

Periodontal diseases involve injuries to the supporting structures of the tooth and, if left untreated, can lead to the loss of the tooth. Regenerative periodontal therapies aim, ideally, at healing all the damaged periodontal tissues and represent a significant clinical and societal challenge for the current ageing population. This review provides a picture of the currently-used biomaterials for periodontal regeneration, including natural and synthetic polymers, bioceramics (e.g., calcium phosphates and bioactive glasses), and composites. Bioactive materials aim at promoting the regeneration of new healthy tissue. Polymers are often used as barrier materials in guided tissue regeneration strategies and are suitable both to exclude epithelial down-growth and to allow periodontal ligament and alveolar bone cells to repopulate the defect. The problems related to the barrier postoperative collapse can be solved by using a combination of polymeric membranes and grafting materials. Advantages and drawbacks associated with the incorporation of growth factors and nanomaterials in periodontal scaffolds are also discussed, along with the development of multifunctional and multilayer implants. Tissue-engineering strategies based on functionally-graded scaffolds are expected to play an ever-increasing role in the management of periodontal defects. Full article