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Hydrogels are known for their high water retention capacity and biocompatibility and have become essential materials in tissue engineering and drug delivery systems. This review explores recent advancements in hydrogel technology, focusing on innovative types such as self-healing, tough, smart, and hybrid hydrogels, each engineered to overcome the limitations of conventional hydrogels. Self-healing hydrogels can autonomously repair structural damage, making them well-suited for applications in dynamic biomedical environments. Tough hydrogels are designed with enhanced mechanical properties, enabling their use in load-bearing applications such as cartilage regeneration. Smart hydrogels respond to external stimuli, including changes in pH, temperature, and electromagnetic fields, making them ideal for controlled drug release tailored to specific medical needs. Hybrid hydrogels, made from both natural and synthetic polymers, combine bioactivity and mechanical resilience, which is particularly valuable in engineering complex tissues. Despite these innovations, challenges such as optimizing biocompatibility, adjusting degradation rates, and scaling up production remain. This review provides an in-depth analysis of these emerging hydrogel technologies, highlighting their transformative potential in both tissue engineering and drug delivery while outlining future directions for their development in biomedical applications. [ABSTRACT FROM AUTHOR]

The goal of this review is to present a wide range of hybrid formulations and composites containing calcium orthophosphates (abbreviated as CaPO4) that are suitable for use in biomedical applications and currently on the market. The bioactive, biocompatible, and osteoconductive properties of various CaPO4-based formulations make them valuable in the rapidly developing field of biomedical research, both in vitro and in vivo. Due to the brittleness of CaPO4, it is essential to combine the desired osteologic properties of ceramic CaPO4 with those of other compounds to create novel, multifunctional bone graft biomaterials. Consequently, this analysis offers a thorough overview of the hybrid formulations and CaPO4-based composites that are currently known. To do this, a comprehensive search of the literature on the subject was carried out in all significant databases to extract pertinent papers. There have been many formulations found with different material compositions, production methods, structural and bioactive features, and in vitro and in vivo properties. When these formulations contain additional biofunctional ingredients, such as drugs, proteins, enzymes, or antibacterial agents, they offer improved biomedical applications. Moreover, a lot of these formulations allow cell loading and promote the development of smart formulations based on CaPO4. This evaluation also discusses basic problems and scientific difficulties that call for more investigation and advancements. It also indicates perspectives for the future. [ABSTRACT FROM AUTHOR]

In exploring the challenges of bone repair and regeneration, this review evaluates the potential of bone tissue engineering (BTE) as a viable alternative to traditional methods, such as autografts and allografts. Key developments in biomaterials and scaffold fabrication techniques, such as additive manufacturing and cell and bioactive molecule-laden scaffolds, are discussed, along with the integration of bio-responsive scaffolds, which can respond to physical and chemical stimuli. These advancements collectively aim to mimic the natural microenvironment of bone, thereby enhancing osteogenesis and facilitating the formation of new tissue. Through a comprehensive combination of in vitro and in vivo studies, we scrutinize the biocompatibility, osteoinductivity, and osteoconductivity of these engineered scaffolds, as well as their interactions with critical cellular players in bone healing processes. Findings from scaffold fabrication techniques and bio-responsive scaffolds indicate that incorporating nanostructured materials and bioactive compounds is particularly effective in promoting the recruitment and differentiation of osteoprogenitor cells. The therapeutic potential of these advanced biomaterials in clinical settings is widely recognized and the paper advocates continued research into multi-responsive scaffold systems. [ABSTRACT FROM AUTHOR]

Mesoporous bioactive glass nanoparticles (MBGNs) have attracted significant attention as multifunctional nanocarriers for various applications in both hard and soft tissue engineering. In this study, multifunctional strontium (Sr)- and zinc (Zn)-containing MBGNs were successfully synthesized via the microemulsion-assisted sol–gel method combined with a cationic surfactant (cetyltrimethylammonium bromide, CTAB). Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs exhibited spherical shapes in the nanoscale range of 100 ± 20 nm with a mesoporous structure. Sr and Zn were co-substituted in MBGNs (60SiO2-40CaO) to induce osteogenic potential and antibacterial properties without altering their size, morphology, negative surface charge, amorphous nature, mesoporous structure, and pore size. The synthesized MBGNs facilitated bioactivity by promoting the formation of an apatite-like layer on the surface of the particles after immersion in Simulated Body Fluid (SBF). The effect of the particles on the metabolic activity of human mesenchymal stem cells was concentration-dependent. The hMSCs exposed to Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs at 200 μg/mL enhanced calcium deposition and osteogenic differentiation without osteogenic supplements. Moreover, the cellular uptake and internalization of Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs in hMSCs were observed. These novel particles, which exhibited multiple functionalities, including promoting bone regeneration, delivering therapeutic ions intracellularly, and inhibiting the growth of Staphylococcus aureus and Escherichia coli, are potential nanocarriers for bone regeneration applications. [ABSTRACT FROM AUTHOR]

The repair of nervous tissue is a critical research field in tissue engineering because of the degenerative process in the injured nervous system. In this review, we summarize the progress of injectable hydrogels using in vitro and in vivo studies for the regeneration and repair of nervous tissue. Traditional treatments have not been favorable for patients, as they are invasive and inefficient; therefore, injectable hydrogels are promising for the treatment of damaged tissue. This review will contribute to a better understanding of injectable hydrogels as potential scaffolds and drug delivery system for neural tissue engineering applications. [ABSTRACT FROM AUTHOR]

Recently, nanotechnologies have become increasingly prominent in the field of bone tissue engineering (BTE), offering substantial potential to advance the field forward. These advancements manifest in two primary ways: the localized application of nanoengineered materials to enhance bone regeneration and their use as nanovehicles for delivering bioactive compounds. Despite significant progress in the development of bone substitutes over the past few decades, it is worth noting that the quest to identify the optimal biomaterial for bone regeneration remains a subject of intense debate. Ever since its initial discovery, poly(lactic-co-glycolic acid) (PLGA) has found widespread use in BTE due to its favorable biocompatibility and customizable biodegradability. This review provides an overview of contemporary advancements in the development of bone regeneration materials using PLGA polymers. The review covers some of the properties of PLGA, with a special focus on modifications of these properties towards bone regeneration. Furthermore, we delve into the techniques for synthesizing PLGA nanoparticles (NPs), the diverse forms in which these NPs can be fabricated, and the bioactive molecules that exhibit therapeutic potential for promoting bone regeneration. Additionally, we addressed some of the current concerns regarding the safety of PLGA NPs and PLGA-based products available on the market. Finally, we briefly discussed some of the current challenges and proposed some strategies to functionally enhance the fabrication of PLGA NPs towards BTE. We envisage that the utilization of PLGA NP holds significant potential as a potent tool in advancing therapies for intractable bone diseases. [ABSTRACT FROM AUTHOR]

Composite hydrogels containing apatite-like particles can act as scaffolds for osteoblast proliferation, with applications in bone tissue engineering. In this respect, porous biocompatible hydrogels were obtained from chitosan, oxidized pullulan, and PVA in different ratios. The stability of the hydrogels was ensured both by covalent bonds between aldehyde groups of oxidized pullulan and free amino groups of chitosan, and by physical bonds formed during freeze–thaw cycles and lyophilization. The deposition of calcium phosphates was performed by alternate soaking of the porous hydrogels into solutions with calcium and phosphate ions, assuring a basic pH required for hydroxyapatite formation. The mineralized hydrogels were characterized using FTIR spectroscopy, scanning electron microscopy, X-ray diffraction, and thermogravimetric analysis, showing that inorganic particles containing between 80 and 92% hydroxyapatite were deposited in a high amount on the pore walls of the polymeric matrix. The composition of the organic matrix influenced the crystallization of calcium phosphates and the mechanical properties of the composite hydrogels. In vitro biological tests showed that mineralized hydrogels support the proliferation of MG-63 osteoblast-like cells to a greater extent compared to pristine hydrogels. [ABSTRACT FROM AUTHOR]

In this work, the effects of weight concentration on the properties of poly(lactide-co-glycolide) polymeric scaffolds prepared by electrospinning are investigated, using four different weight concentrations of poly(lactide-co-glycolide) for the electrospinning solutions (2, 3, 4, 5 wt.%). With increasing concentration of poly(lactide-co-glycolide) in the electrospinning solutions, their viscosity increases significantly. The average fiber diameter of the scaffolds also increases with increasing concentration. Moreover, the tensile strength and maximum elongation at break of the scaffold increase with increasing electrospinning concentration. The prepared scaffolds have hydrophobic properties and their wetting angle does not change with the concentration of the electrospinning solution. All poly(lactide-co-glycolide) scaffolds are non-toxic toward fibroblasts of the cell line 3T3-L1, with the highest numbers of cells observed on the surface of scaffolds prepared from the 2-, 3- and 4-wt.% electrospinning solutions. The results of the analysis of mechanical and biological properties indicate that the poly(lactide-co-glycolide) scaffolds prepared from the 4 wt.% electrospinning solution have optimal properties for future applications in skin tissue engineering. This is due to the fact that the poly(lactide-co-glycolide) scaffolds prepared from the 2 wt.% and 3 wt.% electrospinning solution exhibit low mechanical properties, and 5 wt.% have the lowest porosity values, which might be the cause of their lowest biological properties. [ABSTRACT FROM AUTHOR]

Injectable hydrogels were discovered as attractive materials for bone tissue engineering applications given their outstanding biocompatibility, high water content, and versatile fabrication platforms into materials with different physiochemical properties. However, traditional hydrogels suffer from weak mechanical strength, limiting their use in heavy load-bearing areas. Thus, the fabrication of mechanically robust injectable hydrogels that are suitable for load-bearing environments is of great interest. Successful material design for bone tissue engineering requires an understanding of the composition and structure of the material chosen, as well as the appropriate selection of biomimetic natural or synthetic materials. This review focuses on recent advancements in materials–design considerations and approaches to prepare mechanically robust injectable hydrogels for bone tissue engineering applications. We outline the materials–design approaches through a selection of materials and fabrication methods. Finally, we discuss unmet needs and current challenges in the development of ideal materials for bone tissue regeneration and highlight emerging strategies in the field. [ABSTRACT FROM AUTHOR]

Aerogels are fascinating solid materials known for their highly porous nanostructure and exceptional physical, chemical, and mechanical properties. They show great promise in various technological and biomedical applications, including tissue engineering, and bone and cartilage substitution. To evaluate the bioactivity of bone substitutes, researchers typically conduct in vitro tests using simulated body fluids and specific cell lines, while in vivo testing involves the study of materials in different animal species. In this context, our primary focus is to investigate the applications of different types of aerogels, considering their specific materials, microstructure, and porosity in the field of bone and cartilage tissue engineering. From clinically approved materials to experimental aerogels, we present a comprehensive list and summary of various aerogel building blocks and their biological activities. Additionally, we explore how the complexity of aerogel scaffolds influences their in vivo performance, ranging from simple single-component or hybrid aerogels to more intricate and organized structures. We also discuss commonly used formulation and drying methods in aerogel chemistry, including molding, freeze casting, supercritical foaming, freeze drying, subcritical, and supercritical drying techniques. These techniques play a crucial role in shaping aerogels for specific applications. Alongside the progress made, we acknowledge the challenges ahead and assess the near and far future of aerogel-based hard tissue engineering materials, as well as their potential connection with emerging healing techniques. [ABSTRACT FROM AUTHOR]

A simple and cost-effective method for the fabrication of a safe, dual-responsive, highly stretchable, self-healing and injectable hydrogel is reported based on a combination of dynamic boronate ester bonds and hydrogen bonding interactions. The mechanical properties of the hydrogel are tunable by adjusting the molar ratios between sugar moieties on the polymer and borax. It was remarkable to note that the 2:1 ratio of sugar and borate ion significantly improves the mechanical strength of the hydrogel. The injectability, self-healing and stretchability properties of the hydrogel were also examined. In addition, the impact of the variation of the pH and the addition of free sugar responsiveness of the hydrogel was studied. High MRC-5 cell viability was noticed by the 3D live/dead assay after 24 h cell culture within the hydrogel scaffold. Hence, the developed hydrogels have desirable features that warrant their applications for drug delivery, scaffolds for cell and tissue engineering. [ABSTRACT FROM AUTHOR]

Bioactive glasses (BGs) are especially useful materials in soft and bone tissue engineering and even in dentistry. They can be the solution to many medical problems, and they have a huge role in the healing processes of bone fractures. Interestingly, they can also promote skin regeneration and wound healing. Bioactive glasses are able to attach to the bone tissues and form an apatite layer which further initiates the biomineralization process. The formed intermediate apatite layer makes a connection between the hard tissue and the bioactive glass material which results in faster healing without any complications or side effects. This review paper summarizes the most recent advancement in the preparation of diverse types of BGs, such as silicate-, borate- and phosphate-based bioactive glasses. We discuss their physical, chemical, and mechanical properties detailing how they affect their biological performances. In order to get a deeper insight into the state-of-the-art in this area, we also consider their medical applications, such as bone regeneration, wound care, and dental/bone implant coatings. [ABSTRACT FROM AUTHOR]

Over the last decade, efforts have been oriented toward the development of suitable gels for 3D printing, with controlled morphology and shear-thinning behavior in well-defined conditions. As a multidisciplinary approach to the fabrication of complex biomaterials, 3D bioprinting combines cells and biocompatible materials, which are subsequently printed in specific shapes to generate 3D structures for regenerative medicine or tissue engineering. A major interest is devoted to the printing of biomimetic materials with structural fidelity after their fabrication. Among some requirements imposed for bioinks, such as biocompatibility, nontoxicity, and the possibility to be sterilized, the nondamaging processability represents a critical issue for the stability and functioning of the 3D constructs. The major challenges in the field of printable gels are to mimic at different length scales the structures existing in nature and to reproduce the functions of the biological systems. Thus, a careful investigation of the rheological characteristics allows a fine-tuning of the material properties that are manufactured for targeted applications. The fluid-like or solid-like behavior of materials in conditions similar to those encountered in additive manufacturing can be monitored through the viscoelastic parameters determined in different shear conditions. The network strength, shear-thinning, yield point, and thixotropy govern bioprintability. An assessment of these rheological features provides significant insights for the design and characterization of printable gels. This review focuses on the rheological properties of printable bioinspired gels as a survey of cutting-edge research toward developing printed materials for additive manufacturing. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are one of the leading global causes of morbidity and mortality, posing considerable health and economic burden on patients and medical systems worldwide. This phenomenon is attributed to two main motives: poor regeneration capacity of adult cardiac tissues and insufficient therapeutic options. Thus, the context calls for upgrading treatments to deliver better outcomes. In this respect, recent research has approached the topic from an interdisciplinary perspective. Combining the advances encountered in chemistry, biology, material science, medicine, and nanotechnology, performant biomaterial-based structures have been created to carry different cells and bioactive molecules for repairing and restoring heart tissues. In this regard, this paper aims to present the advantages of biomaterial-based approaches for cardiac tissue engineering and regeneration, focusing on four main strategies: cardiac patches, injectable hydrogels, extracellular vesicles, and scaffolds and reviewing the most recent developments in these fields. [ABSTRACT FROM AUTHOR]

Different parts of bones possess different properties, such as the capacity for remodeling cell content, porosity, and protein composition. For various traumatic or surgical tissue defects, the application of tissue-engineered constructs seems to be a promising strategy. Despite significant research efforts, such constructs are still rarely available in the clinic. One of the reasons is the lack of resorbable materials, whose properties can be adjusted according to the intended tissue or tissue contacts. Here, we present our first results on the development of a toolbox, by which the scaffolds with easily tunable mechanical and biological properties could be prepared. Biodegradable poly(lactic acid) and nanocrystalline cellulose methacrylated particles were obtained, characterized, and used for preparation of three-dimensional scaffolds via cryogelation and 3D printing approaches. The composition of particles-based ink for 3D printing was optimized in order to allow formation of stable materials. Both the modified-particle cytotoxicity and the matrix-supported cell adhesion were evaluated and visualized in order to confirm the perspectives of materials application. [ABSTRACT FROM AUTHOR]

Damage caused by disease or trauma often leads to multi-tissue damage which is both painful and expensive for the patient. Despite the common occurrence of such injuries, reconstruction can be incredibly challenging and often may focus on a single tissue, which has been damaged to a greater extent, rather than the environment as a whole. Tissue engineering offers an approach to encourage repair, replacement, and regeneration using scaffolds, biomaterials and bioactive factors. However, there are many advantages to creating a combined scaffold fabrication method approach that incorporates the treatment and regeneration of multiple tissue types simultaneously. This review provides a guide to combining multiple tissue-engineered scaffold fabrication methods to span several tissue types concurrently. Briefly, a background in the healing and composition of typical tissues targeted in scaffold fabrication is provided. Then, common tissue-engineered scaffold fabrication methods are highlighted, specifically focusing on porosity, mechanical integrity, and practicality for clinical application. Finally, an overview of commonly used scaffold biomaterials and additives is provided, and current research in combining multiple scaffold fabrication techniques is discussed. Overall, this review will serve to bridge the critical gap in knowledge pertaining to combining different fabrication methods for tissue regeneration without disrupting structural integrity and biomaterial properties. [ABSTRACT FROM AUTHOR]

Natural extracellular matrix (ECM) is highly heterogeneous and anisotropic due to the existence of biomacromolecule bundles and pores. Hydrogels have been proposed as ideal carriers for therapeutic cells and drugs in tissue engineering and regenerative medicine. However, most of the homogeneous and isotropic hydrogels cannot fully emulate the hierarchical properties of natural ECM, including the dynamically spatiotemporal distributions of biochemical and biomechanical signals. Biomimetic hierarchical nanocomposite hydrogels have emerged as potential candidates to better recapitulate natural ECM by introducing various nanostructures, such as nanoparticles, nanorods, and nanofibers. Moreover, the nanostructures in nanocomposite hydrogels can be engineered as stimuli-responsive actuators to realize the desirable control of hydrogel properties, thereby manipulating the behaviors of the encapsulated cells upon appropriate external stimuli. In this review, we present a comprehensive summary of the main strategies to construct biomimetic hierarchical nanocomposite hydrogels with an emphasis on the rational design of local hydrogel properties and their stimuli-responsibility. We then highlight cell fate decisions in engineered nanocomposite niches and their recent development and challenges in biomedical applications. [ABSTRACT FROM AUTHOR]

Polymeric hydrogels have drawn considerable attention as a biomedical material for their unique mechanical and chemical properties, which are very similar to natural tissues. Among the conventional hydrogel materials, self-healing hydrogels (SHH) are showing their promise in biomedical applications in tissue engineering, wound healing, and drug delivery. Additionally, their responses can be controlled via external stimuli (e.g., pH, temperature, pressure, or radiation). Identifying a suitable combination of viscous and elastic materials, lipophilicity and biocompatibility are crucial challenges in the development of SHH. Furthermore, the trade-off relation between the healing performance and the mechanical toughness also limits their real-time applications. Additionally, short-term and long-term effects of many SHH in the in vivo model are yet to be reported. This review will discuss the mechanism of various SHH, their recent advancements, and their challenges in tissue engineering, wound healing, and drug delivery. [ABSTRACT FROM AUTHOR]

Various types of materials have been traditionally used to restore damaged bones. In the late 1960s, a strong interest was raised in studying ceramics as potential bone grafts due to their biomechanical properties. A short time later, such synthetic biomaterials were called bioceramics. Bioceramics can be prepared from diverse inorganic substances, but this review is limited to calcium orthophosphate (CaPO4)-based formulations only, due to its chemical similarity to mammalian bones and teeth. During the past 50 years, there have been a number of important achievements in this field. Namely, after the initial development of bioceramics that was just tolerated in the physiological environment, an emphasis was shifted towards the formulations able to form direct chemical bonds with the adjacent bones. Afterwards, by the structural and compositional controls, it became possible to choose whether the CaPO4-based implants would remain biologically stable once incorporated into the skeletal structure or whether they would be resorbed over time. At the turn of the millennium, a new concept of regenerative bioceramics was developed, and such formulations became an integrated part of the tissue engineering approach. Now, CaPO4-based scaffolds are designed to induce bone formation and vascularization. These scaffolds are usually porous and harbor various biomolecules and/or cells. Therefore, current biomedical applications of CaPO4-based bioceramics include artificial bone grafts, bone augmentations, maxillofacial reconstruction, spinal fusion, and periodontal disease repairs, as well as bone fillers after tumor surgery. Prospective future applications comprise drug delivery and tissue engineering purposes because CaPO4 appear to be promising carriers of growth factors, bioactive peptides, and various types of cells. [ABSTRACT FROM AUTHOR]

The use of biopolymers for tissue engineering has recently gained attention due to the need for safer and highly compatible materials. Starch is one of the most used biopolymers for membrane preparation. However, incorporating other polymers into starch membranes introduces improvements, such as better thermal and mechanical resistance and increased water affinity, as we reported in our previous work. There are few reports in the literature on the biocompatibility of starch/chicken gelatin composites. We assessed the in vivo biocompatibility of the five composites (T1–T5) cassava starch/gelatin membranes with subdermal implantations in biomodels at 30, 60, and 90 days. The FT-IR spectroscopy analysis demonstrated the main functional groups for starch and chicken gelatin. At the same time, the thermal study exhibited an increase in thermal resistance for T3 and T4, with a remaining mass (~15 wt.%) at 800 °C. The microstructure analysis for the T2–T4 demonstrated evident roughness changes with porosity presence due to starch and gelatin mixture. The decrease in the starch content in the composites also decreased the gelatinization heats for T3 and T4 (195.67, 196.40 J/g, respectively). Finally, the implantation results demonstrated that the formulations exhibited differences in the degradation and resorption capacities according to the starch content, which is easily degraded by amylases. However, the histological results showed that the samples demonstrated almost complete reabsorption without a severe immune response, indicating a high in vivo biocompatibility. These results show that the cassava starch/chicken gelatin composites are promising membrane materials for tissue engineering applications. [ABSTRACT FROM AUTHOR]

Cell encapsulation has been widely employed in cell therapy, characterization, and analysis, as well as many other biomedical applications. While droplet-based microfluidic technology is advantageous in cell microencapsulation because of its modularity, controllability, mild conditions, and easy operation when compared to other state-of-art methods, it faces the dilemma between high throughput and monodispersity of generated cell-laden microdroplets. In addition, the lack of a biocompatible method of de-emulsification transferring cell-laden hydrogel from cytotoxic oil phase into cell culture medium also hurtles the practical application of microfluidic technology. Here, a novel step-T-junction microchannel was employed to encapsulate cells into monodisperse microspheres at the high-throughput jetting regime. An alginate–gelatin co-polymer system was employed to enable the microfluidic-based fabrication of cell-laden microgels with mild cross-linking conditions and great biocompatibility, notably for the process of de-emulsification. The mechanical properties of alginate-gelatin hydrogel, e.g., stiffness, stress–relaxation, and viscoelasticity, are fully adjustable in offering a 3D biomechanical microenvironment that is optimal for the specific encapsulated cell type. Finally, the encapsulation of HepG2 cells into monodisperse alginate–gelatin microgels with the novel microfluidic system and the subsequent cultivation proved the maintenance of the long-term viability, proliferation, and functionalities of encapsulated cells, indicating the promising potential of the as-designed system in tissue engineering and regenerative medicine. [ABSTRACT FROM AUTHOR]

In our aging society, the number of patients suffering from poorly healing bone defects increases. Bone morphogenetic proteins (BMPs) are used in the clinic to promote bone regeneration. However, poor control of BMP delivery and thus activity necessitates high doses, resulting in adverse effects and increased costs. It has been demonstrated that messenger RNA (mRNA) provides a superior alternative to protein delivery due to local uptake and prolonged expression restricted to the site of action. Here, we present the development of porous collagen scaffolds incorporating peptide-mRNA nanoparticles (NPs). Nanoparticles were generated by simply mixing aqueous solutions of the cationic cell-penetrating peptide PepFect14 (PF14) and mRNA. Peptide-mRNA complexes were uniformly distributed throughout the scaffolds, and matrices fully preserved cell attachment and viability. There was a clear dependence of protein expression on the incorporated amount of mRNA. Importantly, after lyophilization, the mRNA formulation in the collagen scaffolds retained activity also at 4 °C over two weeks. Overall, our results demonstrate that collagen scaffolds incorporating peptide-mRNA complexes hold promise as off-the-shelf functional biomaterials for applications in regenerative medicine and constitute a viable alternative to lipid-based mRNA formulations. [ABSTRACT FROM AUTHOR]

Bones play an important role in maintaining exercise and protecting organs. Bone defect, as a common orthopedic disease in clinics, can cause tremendous damage with long treatment cycles. Therefore, the treatment of bone defect remains as one of the main challenges in clinical practice. Today, with increased incidence of bone disease in the aging population, demand for bone repair material is high. At present, the method of clinical treatment for bone defects including non-invasive therapy and invasive therapy. Surgical treatment is the most effective way to treat bone defects, such as using bone grafts, Masquelet technique, Ilizarov technique etc. In recent years, the rapid development of tissue engineering technology provides a new treatment strategy for bone repair. This review paper introduces the current situation and challenges of clinical treatment of bone defect repair in detail. The advantages and disadvantages of bone tissue engineering scaffolds are comprehensively discussed from the aspect of material, preparation technology, and function of bone tissue engineering scaffolds. This paper also summarizes the 3D printing technology based on computer technology, aiming at designing personalized artificial scaffolds that can accurately fit bone defects. [ABSTRACT FROM AUTHOR]

Self-healing hydrogels and traditional hydrogels both have three-dimensional polymeric networks that are capable of absorbing and retaining a large amount of water. Self-healing hydrogels can heal and restore damage automatically, and they can avoid premature failure of hydrogels caused by mechanical damage after implantation. The formation mechanism of self-healing hydrogels and the factors that hydrogels can load are various. Researchers can design hydrogels to meet the needs of different tissues through the diversity of hydrogels Therefore, it is necessary to summarize different self-healing mechanisms and different factors to achieve different functions. Here, we briefly reviewed the hydrogels designed by researchers in recent years according to the self-healing mechanism of water coagulation. Then, the factors for different functions of self-healing hydrogels in different tissues were statistically analyzed. We hope our work can provide effective support for researchers in the design process of self-healing hydrogel. [ABSTRACT FROM AUTHOR]

The quest for an ideal biomaterial perfectly matching the microenvironment of the surrounding tissues and cells is an endless challenge within biomedical research, in addition to integrating this with a facile and sustainable technology for its preparation. Engineering hydrogels through click chemistry would promote the sustainable invention of tailor-made hydrogels. Herein, we disclose a versatile and facile catalyst-free click chemistry for the generation of an innovative hydrogel by combining chondroitin sulfate (CS) and polyethylene glycol (PEG). Various multi-armed PEG-Norbornene (A-PEG-N) with different molecular sizes were investigated to generate crosslinked copolymers with tunable rheological and mechanical properties. The crosslinked and mechanically stable porous hydrogels could be generated by simply mixing the two clickable Tetrazine-CS (TCS) and A-PEG-N components, generating a self-standing hydrogel within minutes. The leading candidate (TCS-8A-PEG-N (40 kD)), based on the mechanical and biocompatibility results, was further employed as a scaffold to improve wound closure and blood flow in vivo. The hydrogel demonstrated not only enhanced blood perfusion and an increased number of blood vessels, but also desirable fibrous matrix orientation and normal collagen deposition. Taken together, these results demonstrate the potential of the hydrogel to improve wound repair and hold promise for in situ skin tissue engineering applications. [ABSTRACT FROM AUTHOR]

Bone-related defects that cannot heal without significant surgical intervention represent a significant challenge in the orthopedic field. The use of implants for these critical-sized bone defects is being explored to address the limitations of autograft and allograft options. Three-dimensional cellular structures, or bone scaffolds, provide mechanical support and promote bone tissue formation by acting as a template for bone growth. Stress shielding in bones is the reduction in bone density caused by the difference in stiffness between the scaffold and the surrounding bone tissue. This study aimed to reduce the stress shielding and introduce a cellular metal structure to replace defected bone by designing and producing a numerically optimized bone scaffold with an elastic modulus of 15 GPa, which matches the human's cortical bone modulus. Cubic cell and diagonal cell designs were explored. Strut and cell dimensions were numerically optimized to achieve the desired structural modulus. The resulting scaffold designs were produced from stainless steel using laser powder bed fusion (LPBF). Finite element analysis (FEA) models were validated through compression testing of the printed scaffold designs. The structural configuration of the scaffolds was characterized with scanning electron microscopy (SEM). Cellular struts were found to have minimal internal porosity and rough surfaces. Strut dimensions of the printed scaffolds were found to have variations with the optimized computer-aided design (CAD) models. The experimental results, as expected, were slightly less than FEA results due to structural relative density variations in the scaffolds. Failure of the structures was stretch-dominated for the cubic scaffold and bending-dominated for the diagonal scaffold. The torsional and bending stiffnesses were numerically evaluated and showed higher bending and torsional moduli for the diagonal scaffold. The study successfully contributed to minimizing stress shielding in bone tissue engineering. The study also produced an innovative metal cellular structure that can replace large bone segments anywhere in the human body. [ABSTRACT FROM AUTHOR]

Due to their good absorption, satisfactory biocompatibility, and high safety, hydrogels have been widely used in the field of biomedicine, including for drug delivery and tissue regeneration. In this review, we introduce the characteristics and crosslinking methods of natural and synthetic hydrogels. Then, we highlight the design and principle of intelligent hydrogels (i.e., responsive hydrogels) used for drug release. Moreover, we introduce the application of the application of hydrogels in drug release and tissue engineering, and the limitations and research directions of hydrogel in drug release and tissue engineering are also considered. We hope that this review can provide a reference for follow-up studies in related fields. [ABSTRACT FROM AUTHOR]

This study is the first histologic evaluation of an injectable biphasic calcium phosphate (IBCP) in humans six months after socket preservation according to the principles of guided bone regeneration. After tooth extraction, the alveolar ridge of 21 patients was augmented with IBCP (maxresorb® inject) in the test group, while 20 patients in the control group received a bovine xenograft (BX) (cerabone®). Six months after augmentation, a reentry procedure was performed to collect biopsies of regenerated bone for qualitative and quantitative histologic analysis. A total of 20 biopsies were taken for analysis. Qualitative histologic analysis showed complete integration of the biomaterial and no inflammatory tissue reaction, indicating the biocompatibility of the bone grafts and the surrounding tissue in both groups. Histomorphometric analysis showed comparable results in terms of newly formed bone (IBCP: 26.47 ± 14.71%, BX: 30.47 ± 16.39%) and residual biomaterial (IBCP: 13.1 ± 14.07%, BX: 17.89 ± 11.81%), with no significant difference found across groups (p > 0.05, Mann—Whitney U test). Statistical significance between groups was found in the result of soft tissue percentage (IBCP: 60.43 ± 12.73%, BX: 51.64 ± 14.63%, p = 0.046, Mann—Whitney U test). To conclude, IBCP and BX showed good osteoconductivity and biocompatibility with comparable new bone formation six months after alveolar ridge preservation. [ABSTRACT FROM AUTHOR]

Nowadays, the development of new eco-friendly and biocompatible materials using 'green' technologies represents a significant challenge for the biomedical and pharmaceutical fields to reduce the destructive actions of scientific research on the human body and the environment. Thus, bacterial cellulose (BC) has a central place among these novel tailored biomaterials. BC is a non-pathogenic bacteria-produced polysaccharide with a 3D nanofibrous structure, chemically identical to plant cellulose, but exhibiting greater purity and crystallinity. Bacterial cellulose possesses excellent physicochemical and mechanical properties, adequate capacity to absorb a large quantity of water, non-toxicity, chemical inertness, biocompatibility, biodegradability, proper capacity to form films and to stabilize emulsions, high porosity, and a large surface area. Due to its suitable characteristics, this ecological material can combine with multiple polymers and diverse bioactive agents to develop new materials and composites. Bacterial cellulose alone, and with its mixtures, exhibits numerous applications, including in the food and electronic industries and in the biotechnological and biomedical areas (such as in wound dressing, tissue engineering, dental implants, drug delivery systems, and cell culture). This review presents an overview of the main properties and uses of bacterial cellulose and the latest promising future applications, such as in biological diagnosis, biosensors, personalized regenerative medicine, and nerve and ocular tissue engineering. [ABSTRACT FROM AUTHOR]

To recreate or substitute tissue in vivo is a complicated endeavor that requires biomaterials that can mimic the natural tissue environment. Gelatin methacrylate (GelMA) is created through covalent bonding of naturally derived polymer gelatin and methacrylic groups. Due to its biocompatibility, GelMA receives a lot of attention in the tissue engineering research field. Additionally, GelMA has versatile physical properties that allow a broad range of modifications to enhance the interaction between the material and the cells. In this review, we look at recent modifications of GelMA with naturally derived polymers, nanomaterials, and growth factors, focusing on recent developments for vascular tissue engineering and wound healing applications. Compared to polymers and nanoparticles, the modifications that embed growth factors show better mechanical properties and better cell migration, stimulating vascular development and a structure comparable to the natural-extracellular matrix. [ABSTRACT FROM AUTHOR]

The search for higher-quality nanomaterials for medicinal applications continues. There are similarities between electrospun fibers and natural tissues. This property has enabled electrospun fibers to make significant progress in medical applications. However, electrospun fibers are limited to tissue scaffolding applications. When nanoparticles and nanofibers are combined, the composite material can perform more functions, such as photothermal, magnetic response, biosensing, antibacterial, drug delivery and biosensing. To prepare nanofiber and nanoparticle hybrids (NNHs), there are two primary ways. The electrospinning technology was used to produce NNHs in a single step. An alternate way is to use a self-assembly technique to create nanoparticles in fibers. This paper describes the creation of NNHs from routinely used biocompatible polymer composites. Single-step procedures and self-assembly methodologies are used to discuss the preparation of NNHs. It combines recent research discoveries to focus on the application of NNHs in drug release, antibacterial, and tissue engineering in the last two years. [ABSTRACT FROM AUTHOR]

Multifunctional and resistant 3D structures represent a great promise and a great challenge in bone tissue engineering. This study addresses this problem by employing polycaprolactone (PCL)-based scaffolds added with hydroxyapatite (HAp) and superparamagnetic iron oxide nanoparticles (SPION), able to drive on demand the necessary cells and other bioagents for a high healing efficiency. PCL-HAp-SPION scaffolds with different concentrations of the superparamagnetic component were developed through the 3D-printing technology and the specific topographical features were detected by Atomic Force and Magnetic Force Microscopy (AFM-MFM). AFM-MFM measurements confirmed a homogenous distribution of HAp and SPION throughout the surface. The magnetically assisted seeding of cells in the scaffold resulted most efficient for the 1% SPION concentration, providing good cell entrapment and adhesion rates. Mesenchymal Stromal Cells (MSCs) seeded onto PCL-HAp-1% SPION showed a good cell proliferation and intrinsic osteogenic potential, indicating no toxic effects of the employed scaffold materials. The performed characterizations and the collected set of data point on the inherent osteogenic potential of the newly developed PCL-HAp-1% SPION scaffolds, endorsing them towards next steps of in vitro and in vivo studies and validations. [ABSTRACT FROM AUTHOR]

The history of biomaterials dates back to the mists of time: human beings had always used exogenous materials to facilitate wound healing and try to restore damaged tissues and organs. Nowadays, a wide variety of materials are commercially available and many others are under investigation to both maintain and restore bodily functions. Emerging clinical needs forced the development of new biomaterials, and lately discovered biomaterials allowed for the performing of new clinical applications. The definition of biomaterials as materials specifically conceived for biomedical uses was raised when it was acknowledged that they have to possess a fundamental feature: biocompatibility. At first, biocompatibility was mainly associated with biologically inert substances; around the 1970s, bioactivity was first discovered and the definition of biomaterials was consequently extended. At present, it also includes biologically derived materials and biological tissues. The present work aims at walking across the history of biomaterials, looking towards the scientific literature published on this matter. Finally, some current applications of biomaterials are briefly depicted and their future exploitation is hypothesized. [ABSTRACT FROM AUTHOR]

Adequate vascularization is a fundamental prerequisite for bone regeneration, formation and tissue engineering applications. Endothelialization of scaffold materials is a promising strategy to support neovascularization and bone tissue formation. Besides oxygen and nutrition supply, the endothelial network plays an important role concerning osteogenic differentiation of osteoprogenitor cells and consecutive bone formation. In this study we aimed to enhance the growth stimulating, proangiogenic and osteogenic features of the ADSC and HUVEC coculture system by means of VEGFA165 and BMP2 application. We were able to show that sprouting phenomena and osteogenic differentiation were enhanced in the ADSC/HUVEC coculture. Furthermore, apoptosis was unidirectionally decreased in HUVECs, but these effects were not further enhanced upon VEGFA165 or BMP2 application. In summary, the ADSC/HUVEC coculture system per se is a powerful tool for bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

In this study, the nanoscale transformation of the polylactic-co-glycolic acid (PLGA) internal structure, before and after its supercritical carbon dioxide (sc-CO2) swelling and plasticization, followed by foaming after a CO2 pressure drop, was studied by small-angle X-ray scattering (SAXS) for the first time. A comparative analysis of the internal structure data and porosity measurements for PLGA scaffolds, produced by sc-CO2 processing, on a scale ranging from 0.02 to 1000 μm, was performed by SAXS, helium pycnometry (HP), mercury intrusion porosimetry (MIP) and both "lab-source" and synchrotron X-ray microtomography (micro-CT). This approach opens up possibilities for the wide-scale evaluation, computer modeling, and prediction of the physical and mechanical properties of PLGA scaffolds, as well as their biodegradation behavior in the body. Hence, this study targets optimizing the process parameters of PLGA scaffold fabrication for specific biomedical applications. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing is a valuable tool in the production of complexes structures with specific shapes for tissue engineering. Differently from native tissues, the printed structures are static and do not transform their shape in response to different environment changes. Stimuli-responsive biocompatible materials have emerged in the biomedical field due to the ability of responding to other stimuli (physical, chemical, and/or biological), resulting in microstructures modifications. Four-dimensional (4D) printing arises as a new technology that implements dynamic improvements in printed structures using smart materials (stimuli-responsive materials) and/or cells. These dynamic scaffolds enable engineered tissues to undergo morphological changes in a pre-planned way. Stimuli-responsive polymeric hydrogels are the most promising material for 4D bio-fabrication because they produce a biocompatible and bioresorbable 3D shape environment similar to the extracellular matrix and allow deposition of cells on the scaffold surface as well as in the inside. Subsequently, this review presents different bioresorbable advanced polymers and discusses its use in 4D printing for tissue engineering applications. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HA) is widely used in bone tissue engineering for its bioactivity and biocompatibility, and a growing number of researchers are exploring ways to improve the physical properties and biological functions of hydroxyapatite. Up to now, HA has been used as inorganic building blocks for tissue engineering or as nanofillers to blend with polymers, furthermore, various methods such as ion doping or surface modification have been also reported to prepare functionalized HA. In this review, we try to give a brief and comprehensive introduction about HA-based materials, including ion-doped HA, HA/polymer composites and surface modified HA and their applications in bone tissue engineering. In addition, the prospective of HA is also discussed. This review may be helpful for researchers to get a general understanding about the development of hydroxyapatite based materials. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer commonly migrates to the skeleton. Once patients have breast cancer in their bones, their quality of life is poor. Research has shown that the environment and structure of bone helps support metastatic breast cancer cell growth. Current models used in laboratories to study breast cancer that has migrated to bone do not include all the components of what happens in the human body. This is because technology in the past was limiting. Now, however, a new technology exists, called three-dimensional (3D) bioprinting, that "prints" living cells in geometries like the ones within the human body, to replicate a more realistic environment. In cancer research, 3D bioprinting allows researchers to more closely replicate events that occur when cancer cells migrate from a primary location to a secondary site, as well as model events in the environment of the secondary site. 3D bioprinting may also be used instead of animal models in some cases, and may speed up new drug discovery for cancer treatment. Breast cancer commonly metastasizes to bone, resulting in osteolytic lesions and poor patient quality of life. The bone extracellular matrix (ECM) plays a critical role in cancer cell metastasis by means of the physical and biochemical cues it provides to support cellular crosstalk. Current two-dimensional in-vitro models lack the spatial and biochemical complexities of the native ECM and do not fully recapitulate crosstalk that occurs between the tumor and endogenous stromal cells. Engineered models such as bone-on-a-chip, extramedullary bone, and bioreactors are presently used to model cellular crosstalk and bone–tumor cell interactions, but fall short of providing a bone-biomimetic microenvironment. Three-dimensional bioprinting allows for the deposition of biocompatible materials and living cells in complex architectures, as well as provides a means to better replicate biological tissue niches in-vitro. In cancer research specifically, 3D constructs have been instrumental in seminal work modeling cancer cell dissemination to bone and bone–tumor cell crosstalk in the skeleton. Furthermore, the use of biocompatible materials, such as hydroxyapatite, allows for printing of bone-like microenvironments with the ability to be implanted and studied in in-vivo animal models. Moreover, the use of bioprinted models could drive the development of novel cancer therapies and drug delivery vehicles. [ABSTRACT FROM AUTHOR]

One of the most important ideas ever produced by the application of materials science to the medical field is the notion of biomaterials. The nanostructured biomaterials play a crucial role in the development of new treatment strategies including not only the replacement of tissues and organs, but also repair and regeneration. They are designed to interact with damaged or injured tissues to induce regeneration, or as a forest for the production of laboratory tissues, so they must be micro-environmentally sensitive. The existing materials have many limitations, including impaired cell attachment, proliferation, and toxicity. Nanotechnology may open new avenues to bone tissue engineering by forming new assemblies similar in size and shape to the existing hierarchical bone structure. Organic and inorganic nanobiomaterials are increasingly used for bone tissue engineering applications because they may allow to overcome some of the current restrictions entailed by bone regeneration methods. This review covers the applications of different organic and inorganic nanobiomaterials in the field of hard tissue engineering. [ABSTRACT FROM AUTHOR]

Simple Summary: For the research and development of drug discovery, it is of prime importance to construct the three-dimensional (3D) tissue models in vitro. To this end, the enhancement design of cell function and activity by making use of biomaterials is essential. In this review, 3D culture systems of cancer cells combined with several biomaterials for anticancer drug screening are introduced. Anticancer drug screening is one of the most important research and development processes to develop new drugs for cancer treatment. However, there is a problem resulting in gaps between the in vitro drug screening and preclinical or clinical study. This is mainly because the condition of cancer cell culture is quite different from that in vivo. As a trial to mimic the in vivo cancer environment, there has been some research on a three-dimensional (3D) culture system by making use of biomaterials. The 3D culture technologies enable us to give cancer cells an in vitro environment close to the in vivo condition. Cancer cells modified to replicate the in vivo cancer environment will promote the biological research or drug discovery of cancers. This review introduces the in vitro research of 3D cell culture systems with biomaterials in addition to a brief summary of the cancer environment. [ABSTRACT FROM AUTHOR]

Incorporation of 1,25(OH)2 vitamin D3 (vitD3) into tissue-engineered scaffolds could aid the healing of critical-sized bone defects. We hypothesize that shorter applications of vitD3 lead to more osteogenic differentiation of mesenchymal stem cells (MSCs) than a sustained application. To test this, release from a scaffold was mimicked by exposing MSCs to exactly controlled vitD3 regimens. Human adipose stem cells (hASCs) were seeded onto calcium phosphate particles, cultured for 20 days, and treated with 124 ng vitD3, either provided during 30 min before seeding ([200 nM]), during the first two days ([100 nM]), or during 20 days ([10 nM]). Alternatively, hASCs were treated for two days with 6.2 ng vitD3 ([10 nM]). hASCs attached to the calcium phosphate particles and were viable (~75%). Cell number was not affected by the various vitD3 applications. VitD3 (124 ng) applied over 20 days increased cellular alkaline phosphatase activity at Days 7 and 20, reduced expression of the early osteogenic marker RUNX2 at Day 20, and strongly upregulated expression of the vitD3 inactivating enzyme CYP24. VitD3 (124 ng) also reduced RUNX2 and increased CYP24 applied at [100 nM] for two days, but not at [200 nM] for 30 min. These results show that 20-day application of vitD3 has more effect on hASCs than the same total amount applied in a shorter time span. [ABSTRACT FROM AUTHOR]

In oral biology, tissue engineering aims at regenerating functional tissues through a series of key events that occur during alveolar/periodontal tissue formation and growth, by means of scaffolds that deliver signaling molecules and cells. Due to their excellent physicochemical properties and biomimetic features, nanomaterials are attractive alternatives offering many advantages for stimulating cell growth and promoting tissue regeneration through tissue engineering. The main aim of this article was to review the currently available literature to provide an overview of the different nano-scale scaffolds as key factors of tissue engineering for alveolar bone regeneration procedures. In this narrative review, PubMed, Medline, Scopus and Cochrane electronic databases were searched using key words like "tissue engineering", "regenerative medicine", "alveolar bone defects", "alveolar bone regeneration", "nanomaterials", "scaffolds", "nanospheres" and "nanofibrous scaffolds". No limitation regarding language, publication date and study design was set. Hand-searching of the reference list of identified articles was also undertaken. The aim of this article was to give a brief introduction to review the role of different nanoscaffolds for bone regeneration and the main focus was set to underline their role for alveolar bone regeneration procedures. [ABSTRACT FROM AUTHOR]

Phosphoserine modified cements (PMC) exhibit unique properties, including strong adhesion to tissues and biomaterials. While TTCP-PMCs remodel into bone in vivo, little is known regarding the bioactivity and physiochemical changes that occur during resorption. In the present study, changes in the mechanical strength and composition were evaluated for 28 days, for three formulations of αTCP based PMCs. PMCs were significantly stronger than unmodified cement (38–49 MPa vs. 10 MPa). Inclusion of wollastonite in PMCs appeared to accelerate the conversion to hydroxyapatite, coincident with slight decrease in strength. In non-wollastonite PMCs the initial compressive strength did not change after 28 days in PBS (p > 0.99). Dissolution/degradation of PMC was evaluated in acidic (pH 2.7, pH 4.0), and supersaturated fluids (simulated body fluid (SBF)). PMCs exhibited comparable mass loss (<15%) after 14 days, regardless of pH and ionic concentration. Electron microscopy, infrared spectroscopy, and X-ray analysis revealed that significant amounts of brushite, octacalcium phosphate, and hydroxyapatite reprecipitated, following dissolution in acidic conditions (pH 2.7), while amorphous calcium phosphate formed in SBF. In conclusion, PMC surfaces remodel into metastable precursors to hydroxyapatite, in both acidic and neutral environments. By tuning the composition of PMCs, durable strength in fluids, and rapid transformation can be obtained. [ABSTRACT FROM AUTHOR]

Engineering three-dimensional (3D) scaffolds for functional tissue and organ regeneration is a major challenge of the tissue engineering (TE) community. Great progress has been made in developing scaffolds to support cells in 3D, and to date, several implantable scaffolds are available for treating damaged and dysfunctional tissues, such as bone, osteochondral, cardiac and nerve. However, recapitulating the complex extracellular matrix (ECM) functions of native tissues is far from being achieved in synthetic scaffolds. Modular TE is an intriguing approach that aims to design and fabricate ECM-mimicking scaffolds by the bottom-up assembly of building blocks with specific composition, morphology and structural properties. This review provides an overview of the main strategies to build synthetic TE scaffolds through bioactive modules assembly and classifies them into two distinct schemes based on microparticles (µPs) or patterned layers. The µPs-based processes section starts describing novel techniques for creating polymeric µPs with desired composition, morphology, size and shape. Later, the discussion focuses on µPs-based scaffolds design principles and processes. In particular, starting from random µPs assembly, we will move to advanced µPs structuring processes, focusing our attention on technological and engineering aspects related to cell-free and cell-laden strategies. The second part of this review article illustrates layer-by-layer modular scaffolds fabrication based on discontinuous, where layers' fabrication and assembly are split, and continuous processes. [ABSTRACT FROM AUTHOR]

With advances in bone tissue regeneration and engineering technology, various biomaterials as artificial bone substitutes have been widely developed and innovated for the treatment of bone defects or diseases. However, there are no available natural and synthetic biomaterials replicating the natural bone structure and properties under physiological conditions. The characteristic properties of carbon nanotubes (CNTs) make them an ideal candidate for developing innovative biomimetic materials in the bone biomedical field. Indeed, CNT-based materials and their composites possess the promising potential to revolutionize the design and integration of bone scaffolds or implants, as well as drug therapeutic systems. This review summarizes the unique physicochemical and biomedical properties of CNTs as structural biomaterials and reinforcing agents for bone repair as well as provides coverage of recent concerns and advancements in CNT-based materials and composites for bone tissue regeneration and engineering. Moreover, this review discusses the research progress in the design and development of novel CNT-based delivery systems in the field of bone tissue engineering. [ABSTRACT FROM AUTHOR]

Poly(ε-caprolactone) (PCL) is a bioresorbable synthetic polyester with numerous biomedical applications. PCL membranes show great potential in guided tissue regeneration because they are biocompatible, occlusive and space maintaining, but lack osteoconductivity. Therefore, two different types of mesoporous bioactive glasses (SiO2-CaO-P2O5 and SiO2-SrO-P2O5) were synthesized and incorporated in PCL thin membranes by spin coating. To enhance the osteogenic effect of resulting membranes, the bioglasses were loaded with the bisphosphonate drug ibandronate prior to their incorporation in the polymeric matrix. The effect of the composition of the bioglasses as well as the presence of absorbed ibandronate on the physicochemical, cell attachment and differentiation properties of the PCL membranes was evaluated. Both fillers led to a decrease of the crystallinity of PCL, along with an increase in its hydrophilicity and a noticeable increase in its bioactivity. Bioactivity was further increased in the presence of a Sr substituted bioglass loaded with ibandronate. The membranes exhibited excellent biocompatibility upon estimation of their cytotoxicity on Wharton's Jelly Mesenchymal Stromal Cells (WJ-SCs), while they presented higher osteogenic potential in comparison with neat PCL after WJ-SCs induced differentiation towards bone cells, which was enhanced by a possible synergistic effect of Sr and ibandronate. [ABSTRACT FROM AUTHOR]

The discovery of bioactive glasses (BGs) in the late 1960s by Larry Hench et al. was driven by the need for implant materials with an ability to bond to living tissues, which were intended to replace inert metal and plastic implants that were not well tolerated by the body. Among a number of tested compositions, the one that later became designated by the well-known trademark of 45S5 Bioglass® excelled in its ability to bond to bone and soft tissues. Bonding to living tissues was mediated through the formation of an interfacial bone-like hydroxyapatite layer when the bioglass was put in contact with biological fluids in vivo. This feature represented a remarkable milestone, and has inspired many other investigations aiming at further exploring the in vitro and in vivo performances of this and other related BG compositions. This paradigmatic example of a target-oriented research is certainly one of the most valuable contributions that one can learn from Larry Hench. Such a goal-oriented approach needs to be continuously stimulated, aiming at finding out better performing materials to overcome the limitations of the existing ones, including the 45S5 Bioglass®. Its well-known that its main limitations include: (i) the high pH environment that is created by its high sodium content could turn it cytotoxic; (ii) and the poor sintering ability makes the fabrication of porous three-dimensional (3D) scaffolds difficult. All of these relevant features strongly depend on a number of interrelated factors that need to be well compromised. The selected chemical composition strongly determines the glass structure, the biocompatibility, the degradation rate, and the ease of processing (scaffolds fabrication and sintering). This manuscript presents a first general appraisal of the scientific output in the interrelated areas of bioactive glasses and glass-ceramics, scaffolds, implant coatings, and tissue engineering. Then, it gives an overview of the critical issues that need to be considered when developing bioactive glasses for healthcare applications. The aim is to provide knowledge-based tools towards guiding young researchers in the design of new bioactive glass compositions, taking into account the desired functional properties. [ABSTRACT FROM AUTHOR]