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Sanaz Naghavi Alhosseini1, Fathollah Moztarzadeh1, Masoud Mozafari1, Shadnaz Asgari2, Masumeh Dodel3, Ali Samadikuchaksaraei4,5, Saeid Kargozar6, Newsha Jalali11Biomaterials Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, Tehran, Iran; 2Neural Systems and Dynamics Laboratory, Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; 3Nanotechnology and Tissue Engineering Department, Stem Cell Technology Research Center, Tehran, Iran; 4Department of Biotechnology and Cellular and Molecular Research Center, Tehran University of Medical Sciences, Tehran, Iran; 5Biological Systems Engineering Laboratory, Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, London, UK; 6Department of Biotechnology, Tehran University of Medical Sciences, Tehran, IranAbstract: Among several attempts to integrate tissue engineering concepts into strategies to repair different parts of the human body, neuronal repair stands as a challenging area due to the complexity of the structure and function of the nervous system and the low efficiency of conventional repair approaches. Herein, electrospun polyvinyl alcohol (PVA)/chitosan nanofibrous scaffolds have been synthesized with large pore sizes as potential matrices for nervous tissue engineering and repair. PVA fibers were modified through blending with chitosan and porosity of scaffolds was measured at various levels of their depth through an image analysis method. In addition, the structural, physicochemical, biodegradability, and swelling of the chitosan nanofibrous scaffolds were evaluated. The chitosan-containing scaffolds were used for in vitro cell culture in contact with PC12 nerve cells, and they were found to exhibit the most balanced properties to meet the basic required specifications for nerve cells. It could be concluded that addition of chitosan to the PVA scaffolds enhances viability and proliferation of nerve cells, which increases the biocompatibility of the scaffolds. In fact, addition of a small percentage of chitosan to the PVA scaffolds proved to be a promising approach for synthesis of a neural-friendly polymeric blend.Keywords: polyvinyl alcohol, chitosan, polymer blending, nanofibrous scaffolds, neural tissue engineering

Current tissue-engineering approaches require improved biomaterials to balance microstructural and mechanical design criteria. We investigated the effect of adding a naturally occurring polymer, collagen, to a synthetic scaffold made of poly(ε-caprolactone) (PCL). Hybrid PCL-collagen scaffolds with different collagen concentrations were prepared by solvent casting and freeze-drying techniques that included a subsequent chemical cross-linking. Scanning electron microscopy and Fourier transform infrared spectroscopy were used to characterise the microstructure and chemical interactions of the scaffolds. We found that the porous structure of the scaffolds can be tailored by changing the collagen concentration. In addition, we concluded that the scaffolds with 40% collagen exhibit remarkable enhancement in physicochemical and biological characteristics for tendon regeneration. The regenerated tissues were oriented longitudinally in relation to the long axis of the natural tendon, with a substantial number of blood vessels appearing deep within the scaffolds. [ABSTRACT FROM PUBLISHER]

Background: Dental caries is a global public health concern, and early detection is essential. Traditional methods, particularly visual examination, face access and cost challenges. Teledentistry, as an emerging technology, offers the possibility to overcome such barriers, and it must be given high priority for assessment to optimize the performance of oral healthcare systems. The aim of this study was to systematically review the literature evaluating the diagnostic accuracy of teledentistry using photographs taken by Digital Single Lens Reflex (DSLR) and smartphone cameras against visual clinical examination in either primary or permanent dentition., Methods: The review followed PRISMA-DTA guidelines, and the PubMed, Scopus, and Embase databases were searched through December 2022. Original in-vivo studies comparing dental caries diagnosis via images taken by DSLR or smartphone cameras with clinical examination were included. The QUADAS-2 was used to assess the risk of bias and concerns regarding applicability. Meta-analysis was not performed due to heterogeneity among the studies. Therefore, the data were analyzed narratively by the research team., Results: In the 19 studies included, the sensitivity and specificity ranged from 48 to 98.3% and from 83 to 100%, respectively. The variability in performance was attributed to factors such as study design and diagnostic criteria. Specific tooth surfaces and lesion stages must be considered when interpreting outcomes. Using smartphones for dental photography was common due to the convenience and accessibility of these devices. The employment of mid-level dental providers for remote screening yielded comparable results to those of dentists. Potential bias in patient selection was indicated, suggesting a need for improvements in study design., Conclusion: The diagnostic accuracy of teledentistry for caries detection is comparable to that of traditional clinical examination. The findings establish teledentistry's effectiveness, particularly in lower income settings or areas with access problems. While the results of this review is promising, conducting several more rigorous studies with well-designed methodologies can fully validate the diagnostic accuracy of teledentistry for dental caries to make oral health care provision more efficient and equitable., Registration: This study was registered with PROSPERO (CRD42023417437)., (© 2024. The Author(s).)

To reduce and prevent postsurgical adhesions, a variety of scientific approaches have been suggested and applied. This includes the use of advanced therapies like tissue-engineered (TE) biomaterials and scaffolds. Currently, biocompatible antiadhesive constructs play a pivotal role in managing postoperative adhesions and several biopolymer-based products, namely hyaluronic acid (HA) and polyethylene glycol (PEG), are available on the market in different forms (e.g., sprays, hydrogels). TE polymeric constructs are usually associated with critical limitations like poor biocompatibility and mechanical properties. Hence, biocompatible nanocomposites have emerged as an advanced therapy for postoperative adhesion treatment, with hydrogels and electrospun nanofibers among the most utilized antiadhesive nanocomposites for in vitro and in vivo experiments. Recent studies have revealed that nanocomposites can be engineered to generate smart three-dimensional (3D) scaffolds that can respond to different stimuli, such as pH changes. Additionally, nanocomposites can act as multifunctional materials for the prevention of adhesions and bacterial infections, as well as tissue healing acceleration. Still, more research is needed to reveal the clinical potential of nanocomposite constructs and the possible success of nanocomposite-based products in the biomedical market.

Bioactive glasses (BGs) arewell known for their successful applications in tissue engineering and regenerative medicine. Recent experimental studies have shown their potential usability in oncology, either alone or in combination with other biocompatible materials, such as biopolymers. Direct contact with BG particles has been found to cause toxicity and death in specific cancer cells (bone-derived neoplastic stromal cells) in vitro. Nanostructured BGs (NBGs) can be doped with anticancer elements, such as gallium, to enhance their toxic effects against tumor cells. However, the molecular mechanisms and intracellular targets for anticancer compositions of NBGs require further clarification. NBGs have been successfully evaluated for use in various well-established cancer treatment strategies, including cancer hyperthermia, phototherapy, and anticancer drug delivery. Existing results indicate that NBGs not only enhance cancer cell death, but can also participate in the regeneration of lost healthy tissues. However, the application of NBGs in oncology is still in its early stages, and numerous unanswered questions must be addressed. For example, the impact of the composition, biodegradation, size, and morphology of NBGs on their anticancer efficacy should be defined for each type of cancer and treatment strategy. Moreover, it should be more clearly assessed whether NBGs can shrink tumors, slow/stop cancer progression, or cure cancer completely. In this regard, the use of computational studies (in silico methods) is highly recommended to design the most effective glass formulations for cancer therapy approaches and to predict, to some extent, the relevant properties, efficacy, and outcomes. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease., (© 2023 Wiley Periodicals LLC.)

There is an increasing trend toward the application of bioactive glasses in different areas of biomedicine, including tissue engineering and oncology. The reason for this increase is mostly attributed to the inherent properties of BGs, such as excellent biocompatibility, and the ease of tailoring their properties by changing, for example, the chemical composition. Previous experiments have demonstrated that the interactions between BGs and their ionic dissolution products, and mammalian cells, can affect and change cellular behaviors, and thereby govern the performance of living tissues. However, limited research exists on their critical role in the production and secretion of extracellular vesicles (EVs) such as exosomes. Exosomes are nanosized membrane vesicles that carry various therapeutic cargoes such as DNA, RNA, proteins, and lipids, and thereby can govern cell-cell communication and subsequent tissue responses. The use of exosomes is currently considered a cell-free approach in tissue engineering strategies, due to their positive roles in accelerating wound healing. On the other hand, exosomes are known as key players in cancer biology (e.g., progression and metastasis), due to their capability to carry bioactive molecules between tumor cells and normal cells. Recent studies have demonstrated that the biological performance of BGs, including their proangiogenic activity, is accomplished with the help of exosomes. Indeed, therapeutic cargos (e.g., proteins) produced in BG-treated cells are transferred by a specific subset of exosomes toward target cells and tissues, and lead to a biological phenomenon. On the other hand, BGs are suitable delivery vehicles that can be utilized for the targeted delivery of exosomes to cells and tissues of interest. Therefore, it seems necessary to have a deeper understanding of the potential effects of BGs in the production of exosomes in cells that are involved in tissue repair and regeneration (mostly mesenchymal stem cells), as well as in those that play roles in cancer progression (e.g., cancer stem cells). This review aims to present an updated report on this critical issue, to provide a roadmap for future research in the fields of tissue engineering and regenerative medicine.

Skin tissue engineering has progressed from simple wound dressings to biocompatible materials with desired physico-chemical properties that can deliver regenerative biomolecules. This study describes using a novel biomimetic hybrid scaffold of decellularized dermis/collagen fibers that can continuously deliver stromal cell-derived factor-1 alpha (SDF-1α) for skin regeneration. In diabetic rat models, the idea that sustained SDF-1α infusion could increase the recruitment of CXCR4-positive cells at the injury site and improve wound regeneration was investigated. The morphology of the scaffold, its biocompatibility, and the kinetics of SDF-1 release were all assessed. SDF-1α was successfully incorporated into collagen nanofibers, resulting in a 200-h continuous release profile. The microscopic observations exhibited that cells are attached and proliferated on proposed scaffolds. As evaluated by in vivo study and histological examination, fabricated scaffold with SDF-1α release capacity exhibited a remarkably more robust ability to accelerate wound regeneration than the control group. Besides, the SDF-1α-loaded scaffold demonstrated functional effects on the proliferation and recruitment of CD31 and CXCR4-positive cells in the wound bed. Additionally, no adverse effects such as hyperplasia or scarring were found during the treatment period. It may be concluded that the fabricated hybrid scaffold based on natural polymer opens up a new option for topical administration of bioactive molecules. We believe the SDF-1α-loaded hybrid scaffold has promise for skin tissue engineering., (© 2023. Controlled Release Society.)

In this study, zinc (Zn)- and copper (Cu)-doped 13-93B3 borate mesoporous bioactive glasses (MBGs) were successfully synthesized using nitrate precursors in the presence of Pluronic P123. We benefited from computational approaches for predicting and confirming the experimental findings. The changes in the dynamic surface tension (SFT) of simulated body fluid (SBF) were investigated using the Du Noüy ring method to shed light on the mineralization process of hydroxyapatite (HAp) on the glass surface. The obtained MBGs were in a glassy state before incubation in SBF. The formation of an apatite-like layer on the SBF-incubated borate glasses was investigated by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The incorporation of Zn and Cu into the basic composition of 13-93B3 glass led to changes in the glass transition temperature (Tg) (773 to 556 °C), particle size (373 to 64 nm), zeta potential (−12 to −26 mV), and specific surface area (SBET) (54 to 123 m2/g). Based on the K-means algorithm and chi-square automatic interaction detection (CHAID) tree, we found that the SFT of SBF is an important factor for the prediction and confirmation of the HAp mineralization process on the glasses. Furthermore, we proposed a simple calculation, based on SFT variation, to quantify the bioactivity of MBGs. The doped and dopant-free borate MBGs could enhance the proliferation of mouse fibroblast L929 cells at a concentration of 0.5 mg/mL. These glasses also induced very low hemolysis (<5%), confirming good compatibility with red blood cells. The results of the antibacterial test revealed that all the samples could significantly decrease the viability of Pseudomonas aeruginosa. In summary, we showed that Cu-/Zn-doped borate MBGs can be fabricated using a cost-effective method and also show promise for wound healing/skin tissue engineering applications, as especially supported by the cell test with fibroblasts, good compatibility with blood, and antibacterial properties.

Promoting bone healing is a key challenge in our society that can be tackled by developing new implantable biomaterials provided with regenerative properties. In this work, the coating of three-dimensional porous glass-derived scaffolds with hyaluronic acid (HA)-fatty acids was investigated for the first time. The starting scaffolds, based on bioactive silicate glass, were produced by foam replication followed by sintering; then, HA-palmitate and HA-oleate conjugate coatings were deposited on the scaffold struts through a dipping procedure. FT-IR analysis confirmed the successful deposition of the coatings on the surface and struts of the scaffolds, the foam-like architecture of which was maintained as assessed by SEM investigations. The in vitro bioactivity of the HA-fatty-acid-coated scaffolds was studied by immersion tests in simulated body fluid and the subsequent evaluation of hydroxyapatite formation. The deposition of the polymeric coating did not inhibit the apatite-forming ability of scaffolds, as revealed by the formation of nanostructured hydroxyapatite agglomerates 48 h from immersion. These promising results motivate further investigation of these novel bioactive systems, which are expected to combine the bone-bonding properties of the glass with the wound-healing promotion carried out by the polymeric conjugates.

Tissue engineering (TE) and regenerative medicine have held great promises for the repair and regeneration of damaged tissues and organs. Additive manufacturing has recently appeared as a versatile technology in TE strategies that enables the production of objects through layered printing. By applying 3D printing and bioprinting, it is now possible to make tissue-engineered constructs according to desired thickness, shape, and size that resemble the native structure of lost tissues. Up to now, several organic and inorganic materials were used as raw materials for 3D printing; bioactive glasses (BGs) are among the most hopeful substances regarding their excellent properties (e.g., bioactivity and biocompatibility). In addition, the reported studies have confirmed that BG-reinforced constructs can improve osteogenic, angiogenic, and antibacterial activities. This review aims to provide an up-to-date report on the development of BG-containing raw biomaterials that are currently being employed for the fabrication of 3D printed scaffolds used in tissue regeneration applications with a focus on their advantages and remaining challenges., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Elevated levels of oxidative stress are usually observed following injuries, leading to impaired tissue repair due to oxidation-related chronic inflammation. Several attempts have been made to manage this unfavorable situation, and the use of biomaterials with antioxidant activity is showing great promise in tissue engineering and regenerative medicine approaches. Bioactive glasses (BGs) are a versatile group of inorganic substances that exhibit an outstanding regenerative capacity for both hard and soft damaged tissues. The chemical composition of BGs provides a great opportunity for imparting specific biological activities to them. On this point, BGs may easily become antioxidant substances through simple physicochemical modifications. For example, particular antioxidant elements (mostly cerium (Ce)) can be added to the basic composition of the glasses. On the other hand, grafting natural antioxidant substances (e.g., polyphenols) on the BG surface is feasible for making antioxidant substitutes with promising results in vitro. Mesoporous BGs (MBGs) were demonstrated to have unique merits compared with melt-derived BGs since they make it possible to load antioxidants and deliver them to the desired locations. However, there are actually limited in vivo experimental studies on the capability of modified BGs for scavenging free radicals (e.g., reactive oxygen species (ROS)). Therefore, more research is required to determine the actual potential of BGs in decreasing oxidative stress and subsequently improving tissue repair and regeneration. The present work aims to highlight the potential of different types of BGs in modulating oxidative stress and subsequently improving tissue healing.

In this study, we successfully utilized nitrate precursors for the synthesis of silver (Ag)-doped borate-based mesoporous bioactive glass (MBGs) based on the 1393B3 glass formulation in the presence of a polymeric substrate (polyvinyl alcohol (PVA)) as a stabilizer of boric acid. The X-ray diffraction (XRD) analysis confirmed the glassy state of all the MBGs. The incorporation of 7.5 mol% Ag into the glass composition led to a decrease in the glass transition temperature (T g ). Improvements in the particle size, zeta potential, surface roughness, and surface area values were observed in the Ag-doped MBGs. The MBGs (1 mg/mL) had no adverse effect on the viability of fibroblasts. In addition, Ag-doped MBGs exhibited potent antibacterial activity against gram-positive and gram-negative species. In summary, a modified sol-gel method was confirmed for producing the Ag-doped 1393B3 glasses, and the primary in vitro outcomes hold promise for conducting in vivo studies for managing burns.

Skin defects are among the most prevalent and serious problems worldwide; it is necessary to provide appropriate coverage in order to reduce possible mortality risk and accelerate wound healing. In this study, we have designed a series of extracellular matrix (ECM)-mimicking nanofibrous scaffolds composed of both natural (gelatin (GEL) and chitosan (CS)) and synthetic (poly(ε-caprolactone) (PCL) and poly (vinyl alcohol) (PVA)) polymers. The 3D constructs (PCL/GEL-PVA/CS) were reinforced with 5% (w/w) of platelet lysate (PL) for promoting cells viability and mobility. The physicochemical characterizations of nanofibers confirmed suitable hydrophilicity, controlled degradability, and water uptake of 250.31 ± 62.74%, and 222.425 ± 86.37% for the PCL/GEL-PVA/CS and PCL/GEL-PVA/CS + PL nanofibers, respectively. The scanning electron microscopy (SEM) images exhibited the mean diameter of the fabricated fibers (PCL/GEL-PVA/CS) in the range of 454 ± 257 nm. The blended samples (PCL/GEL-PVA/CS) were also confirmed to have higher ultimate tensile stress (UTS) (3.71 ± 0.32 MPa). From a biological point of view, the fabricated scaffolds showed appropriate blood compatibility and great potential to avoid bacterial invasion. Altogether, the tailored fabrication of PCL/GEL-PVA/CS nanofibers may be considered a suitable construct for epidermal wound healing., Competing Interests: Conflict of Interest The authors declare no conflict of interest regarding the publication of this work, (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Beyond their well-known applications in bone tissue engineering, hydroxyapatite nanoparticles (HAp NPs) have also been showing great promise for improved cancer therapy. The chemical structure of HAp NPs offers excellent possibilities for loading and delivering a broad range of anticancer drugs in a sustained, prolonged, and targeted manner and thus eliciting lower complications than conventional chemotherapeutic strategies. The incorporation of specific therapeutic elements into the basic composition of HAp NPs is another approach, alone or synergistically with drug release, to provide advanced anticancer effects such as the capability to inhibit the growth and metastasis of cancer cells through activating specific cell signaling pathways. HAp NPs can be easily converted to smart anticancer agents by applying different surface modification treatments to facilitate the targeting and killing of cancer cells without significant adverse effects on normal healthy cells. The applications in cancer diagnosis for magnetic and nuclear in vivo imaging are also promising as the detection of solid tumor cells is now achievable by utilizing superparamagnetic HAp NPs. The ongoing research emphasizes the use of HAp NPs in fabricating three-dimensional scaffolds for the treatment of cancerous tissues or organs, promoting the regeneration of healthy tissue after cancer detection and removal. This review provides a summary of HAp NP applications in cancer theranostics, highlighting the current limitations and the challenges ahead for this field to open new avenues for research.

The timely management of skin wounds has been an unmet clinical need for centuries. While there have been several attempts to accelerate wound healing and reduce the cost of hospitalisation and the healthcare burden, there remains a lack of efficient and effective wound healing approaches. In this regard, stem cell-based therapies have garnered an outstanding position for the treatment of both acute and chronic skin wounds. Stem cells of different origins (e.g., embryo-derived stem cells) have been utilised for managing cutaneous lesions; specifically, mesenchymal stem cells (MSCs) isolated from foetal (umbilical cord) and adult (bone marrow) tissues paved the way to more satisfactory outcomes. Since angiogenesis plays a critical role in all four stages of normal wound healing, recent therapeutic approaches have focused on utilising stem cells for inducing neovascularisation. In fact, stem cells can promote angiogenesis via either differentiation into endothelial lineages or secreting pro-angiogenic exosomes. Furthermore, particular conditions (e.g., hypoxic environments) can be applied in order to boost the pro-angiogenic capability of stem cells before transplantation. For tissue engineering and regenerative medicine applications, stem cells can be combined with specific types of pro-angiogenic biocompatible materials (e.g., bioactive glasses) to enhance the neovascularisation process and subsequently accelerate wound healing. As such, this review article summarises such efforts emphasising the bright future that is conceivable when using pro-angiogenic stem cells for treating acute and chronic skin wounds., (© 2022 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

The human amniotic membrane (HAM) is widely used as a natural scaffold in tissue engineering due to its excellent biological characteristics, including anti-microbial, anti-inflammatory, low immunogenicity, and pro-angiogenic properties. This study aimed to develop simple and cost-effective protocols for the decellularization of HAM (d-HAM) using detergent-free methods, i.e., mechanical force (brushing) and physical treatment (heating 45-55 °C). The effectiveness of the methods of interest was compared with a chemical-based approach (EDTA + NaOH + NH 4 Cl). The prepared d-HAMs were characterized using a series of physico-chemical, mechanical, and biological evaluations. The results from DAPI staining revealed that the chemical method could completely remove epithelial cells from HAM, while the two other approaches only reduced the number of epithelial cells. All three decellularization methods led to a sharp reduction (P < 0.001) in the DNA content of the tissue samples (< 50 ng/mg). Histological evaluations showed the preservation of the d-HAMs' integrity along with the conservation of collagen and glycosaminoglycans (GAGs). Although the chemical method caused the lowest mechanical deterioration (3.55 MPa in ultimate tensile stress), the mechanical method preserved the highest hydroxyproline levels (3.13 mg/mL). On the other hand, the physical method (heating to 45 and 50 °C) encouraged cell proliferation more than the chemical and mechanical approaches. All of the samples proved to be suitable for cell attachment and could induce cell migration. In conclusion, the present study showed that the use of detergent-free protocols is applicable for the decellularization of HAM, and the obtained tissues may be considered as inexpensive dressings for numerous tissue engineering applications., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The utilization of bioactive glasses (BGs) in cancer therapy has recently become quite promising; herein, a series of Fe-doped mesoporous 45S5-based BGs (MBGs) were synthesized via the sol-gel method in the presence of Pluronic P123 as a soft template. The physico-chemical and biological properties of the prepared glasses were well-characterized through structural assessments, thermal analyses, and electron microscopic studies. Electrochemical analyses, including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), were also performed to investigate the actual potential of the Fe 2 O 3 -containing MBGs in modulating the Fenton's reaction. The XRD results confirmed the glassy state of the Fe-doped samples before immersion in simulated body fluid (SBF). The prepared Fe-doped MBGs exhibited a particle size in the range of 11-86 nm, surface charge of 27-30 mV, S BET of 95-306 m 2 /g, and M s of 0.08 to 0.2 emu/g. The incorporation of Fe 2 O 3 led to a negligible decrease in the bioactivity of the glasses. The CV analysis indicated that the Fe-doped MBGs could generate H 2 O 2 in a cathodic potential higher than -0.2 V (vs. Ag/AgCl) in the O 2 -saturated Na 2 SO 4 solution. Additionally, the data of the EIS test revealed that the Fe 2 O 3 -doped MBGs could increase the standard rate constant of Electro-Fenton's (EF) reaction up to 38.44 times as compared with the Fe-free glasses. In conclusion, Fe-doped 45S5-derived glasses may be useful in cancer therapy strategies due to their capability of activating Fenton's reaction and subsequent production of reactive oxygen species (ROS) such as • OH free radicals., (Copyright © 2022. Published by Elsevier Inc.)

The use of bioactive glasses (BGs) has been quite fruitful in hard tissue engineering due to the capability of these materials to bond to living bone. In this work, a melt-derived magnesium (Mg)-doped BG (composition: 45SiO 2 -3P 2 O 5 -26CaO-15Na 2 O-7MgO-4K 2 O (mol.%)) was synthesized for being used in bone reconstruction. The prepared BGs were then manufactured as three-dimensional (3D) scaffolds by using the sponge replica approach. The microstructure of the samples was assessed by X-ray diffraction (XRD) and the surface morphology was observed by using scanning electron microscopy (SEM). The in vitro bioactivity and the release of osteo-stimulatory Mg 2+ ions from the prepared samples were investigated over 7 days of incubation in simulated body fluids (SBF). In vitro cellular analyses revealed the compatibility of the Mg-doped BGs with human osteosarcoma cells (MG-63 cell line). Moreover, the Mg-doped BGs could induce bone nodule formation in vitro and improve the migratory ability of human umbilical vein endothelial cells (HUVECs). In vivo osteogenic capacity was further evaluated by implanting the BG-derived scaffolds into surgically-created critical-size bone defects in rats. Histological and immunohistological observations revealed an appropriate bone regeneration in the animals receiving the glass-based scaffolds after 12 weeks of surgery. In conclusion, our study indicates the effectiveness of the Mg-doped BGs in stimulating osteogenesis in both in vitro and in vivo conditions.

Objective: Meniscus injuries in the inner avascular zone have weak intrinsic self-healing capacity and often progress to osteoarthritis. This study focused on evaluating the effects of polycaprolactone/silk fibroin/gelatin/ascorbic acid (PCL/SF/Gel/AA) composite scaffolds seeded with adipose-derived mesenchymal stem cells (ASCs), in the meniscus repair., Design: To this end, composite scaffolds were cross-linked using N -hydroxysuccinimide and 1-ethyl-3-(3-dimethyl-aminopropyl)-1-carbodiimide hydrochloride. Scaffolds were then characterized by scanning electron microscope, mechanical tests, total antioxidant capacity, swelling, and toxicity tests., Results: The PCL/SF/Gel/AA scaffolds exhibited suitable mechanical properties. Furthermore, vitamin C rendered them the highest antioxidant capacity. The PCL/SF/Gel/AA scaffolds also showed good biocompatibility and proliferation for chondrocytes. Moreover, the PCL/SF/Gel/AA scaffold seeded with allogeneic ASCs was engrafted in New Zealand rabbits who underwent unilateral punch defect in the medial meniscus of the right knee. After 2 months postimplantation, macroscopic and histologic studies for new meniscus cartilage were performed., Conclusions: Our results indicated that the PCL/SF/Gel/AA composite scaffolds seeded with allogeneic ASCs could successfully improve meniscus healing in damaged rabbits.

Exploring new therapies for managing skin wounds is under progress and, in this regard, mesoporous silica nanoparticles (MSNs) and mesoporous bioactive glasses (MBGs) offer great opportunities in treating acute, chronic, and malignant wounds. In general, therapeutic effectiveness of both MSNs and MBGs in different formulations (fine powder, fibers, composites etc.) has been proved over all the four stages of normal wound healing including hemostasis, inflammation, proliferation, and remodeling. The main merits of these porous substances can be summarized as their excellent biocompatibility and the ability of loading and delivering a wide range of both hydrophobic and hydrophilic bioactive molecules and chemicals. In addition, doping with inorganic elements (e.g., Cu, Ga, and Ta) into MSNs and MBGs structure is a feasible and practical approach to prepare customized materials for improved skin regeneration. Nowadays, MSNs and MBGs could be utilized in the concept of targeted therapy of skin malignancies (e.g., melanoma) by grafting of specific ligands. Since potential effects of various parameters including the chemical composition, particle size/morphology, textural properties, and surface chemistry should be comprehensively determined via cellular in vitro and in vivo assays, it seems still too early to draw a conclusion on ultimate efficacy of MSNs and MBGs in skin regeneration. In this regard, there are some concerns over the final fate of MSNs and MBGs in the wound site plus optimal dosages for achieving the best outcomes that deserve careful investigation in the future.

Surface treatment of biomaterials could enable reliable and quick cellular responses and accelerate the healing of the host tissue. Here, a series of calcium phosphates (CaPs) were surface treated by hydrogen peroxide (H 2 O 2 ) and the treatment effects were physicochemically and biologically evaluated. For this aim, as-synthesized CaPs doped with strontium (Sr 2+ ), iron (Fe 2+ ), silicon (Si 4+ ), and titanium (Ti 4+ ) ions were sonicated in H 2 O 2 media. The results showed that the specific surface area and zeta potential values of the surface-treated CaPs were increased by ~50% and 25%, respectively. Moreover, the particle size and the band-gap (Eg) values of the surface-treated CaPs were decreased by ~25% and ~2-10%, respectively. The concentration of oxygen vacancies was increased in the surface-treated samples, which was confirmed by the result of ultraviolet (UV), photoluminescence (PL), Commission Internationale de l'éclairage (CIE 1931), and X-ray photoelectron spectroscopy (XPS) analyses. In vitro cellular assessments of surface-treated CaPs exhibited an improvement in cytocompatibility, reactive oxygen species generation (ROS) capacity, bone nodule formation, and the migration of cells up to ~8%, 20%, 35%, and 13%, respectively. Based on the obtained data, it can be stated that improved physicochemical properties of H 2 O 2 -treated CaPs could increase the ROS generation and subsequently enhance the biological activities. In summary, the results demonstrate the notable effect of the H 2 O 2 surface treatment method on improving surface properties and biological performance of CaPs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Finding effective treatments for cardiac diseases is among the hottest subjects in medicine; cell-based therapies have brought great promises for managing a broad range of life-threatening heart complications such as myocardial infarction. After clarifying the critical role of angiogenesis in tissue repair and regeneration, various stem/progenitor cell were utilized to accelerate the healing of injured cardiac tissue. Embryonic, fetal, adult, and induced pluripotent stem cells have shown the appropriate proangiogenic potential for tissue repair strategies. The capability of stem cells for differentiating into endothelial lineages was initially introduced as the primary mechanism involved in improving angiogenesis and accelerated heart tissue repair. However, recent studies have demonstrated the leading role of paracrine factors secreted by stem cells in advancing neo-vessel formation. Genetically modified stem cells are also being applied for promoting angiogenesis regarding their ability to considerably overexpress and secrete angiogenic bioactive molecules. Yet, conducting further research seems necessary to precisely identify molecular mechanisms behind the proangiogenic potential of stem cells, including the signaling pathways and regulatory molecules such as microRNAs. In conclusion, stem cells' pivotal roles in promoting angiogenesis and consequent improved cardiac healing and remodeling processes should not be ignored, especially in the case of stem cell-derived extracellular vesicles., (© 2021 International Union of Biochemistry and Molecular Biology.)

The use of naturally occurring materials in biomedicine has been increasingly attracting the researchers' interest and, in this regard, gum tragacanth (GT) is recently showing great promise as a therapeutic substance in tissue engineering and regenerative medicine. As a polysaccharide, GT can be easily extracted from the stems and branches of various species of Astragalus. This anionic polymer is known to be a biodegradable, non-allergenic, non-toxic, and non-carcinogenic material. The stability against microbial, heat and acid degradation has made GT an attractive material not only in industrial settings (e.g., food packaging) but also in biomedical approaches (e.g., drug delivery). Over time, GT has been shown to be a useful reagent in the formation and stabilization of metal nanoparticles in the context of green chemistry. With the advent of tissue engineering, GT has also been utilized for the fabrication of three-dimensional (3D) scaffolds applied for both hard and soft tissue healing strategies. However, more research is needed for defining GT applicability in the future of biomedical engineering. On this object, the present review aims to provide a state-of-the-art overview of GT in biomedicine and tries to open new horizons in the field based on its inherent characteristics.

The fight against cancer is an old challenge for mankind. Apart from surgery and chemotherapy, which are the most common treatments, use of radiation represents a promising, less invasive strategy that can be performed both from the outside or inside the body. The latter approach, also known as brachytherapy, relies on the use of implantable beta-emitting seeds or microspheres for killing cancer cells. A set of radioactive glasses have been developed for this purpose but their clinical use is still mainly limited to liver cancer. This review paper provides a picture of the biomedical glasses developed and experimented for brachytherapy so far, focusing the discussion on the production methods and current limitations of the available options to their diffusion in clinical practice. Highly-durable neutron-activatable glasses in the yttria-alumina-silica oxide system are typically preferred in order to avoid the potentially-dangerous release of radioisotopes, while the compositional design of degradable glass systems suitable for use in radiotherapy still remains a challenge and would deserve further investigation in the near future., Competing Interests: The authors declare no conflict of interest.

Copper is one of the most used therapeutic metallic elements in biomedicine, ranging from antibacterial approaches to cancer theranostics. This element could be easily incorporated into different types of biomaterials; specifically, copper-doped bioactive glasses (BGs) provide great opportunities for biomedical engineers and clinicians as regards their excellent biocompatibility and regenerative potential. Although copper-incorporated BGs are mostly used in bone tissue engineering, accelerated soft tissue healing is achievable, too, with interesting potentials in wound treatment and skin repair. Copper can modulate the physico-chemical properties of BGs (e.g., reactivity with bio-fluids) and improve their therapeutic potential. Improving cell proliferation, promoting angiogenesis, reducing or even prohibiting bacterial growth are counted as prominent biological features of copper-doped BGs. Recent studies have also suggested the suitability of copper-doped BGs in cancer photothermal therapy (PTT). However, more research is needed to determine the extent to which copper-doped BGs are actually applicable for tissue engineering and regenerative medicine strategies in the clinic. Moreover, copper-doped BGs in combination with polymers may be considered in the future to produce relatively soft, pliable composites and printable inks for use in biofabrication., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Quantum dots (QDs) are semiconductor materials that have gained great interest due to their unique characteristics like optical properties. They are extensively being used in different areas, including solar cells, light-emitting diodes, laser technology, as well as biological and biomedical applications. In this review, comprehensive information about different aspects of QDs is provided, including their types and classifications, synthesis approaches, in vitro and in vivo toxicity, biological applications, and potentials in clinical applications. With a focus on the biological aspects, the respective in vitro and in vivo studies are collected and presented. Various surface modifications on QDs are discussed as directly influencing their properties like toxicity and optical abilities. Given the promising results, these materials are clinically used for targeted molecular therapy and imaging. However, there are a large number of questions that should be addressed before the wide application of QDs in a clinical setting. Regarding the existing barriers to QDs, suggestions are given and discussed to present an appropriate route for the clinical use of these materials., (© 2020 Wiley-VCH GmbH.)

Several biocompatible materials have been applied for managing soft tissue lesions; cerium oxide nanoparticles (CNPs, or nanoceria) are among the most promising candidates due to their outstanding properties, including antioxidant, anti-inflammatory, antibacterial, and angiogenic activities. Much attention should be paid to the physical properties of nanoceria, since most of its biological characteristics are directly determined by some of these relevant parameters, including the particle size and shape. Nanoceria, either in bare or functionalized forms, showed the excellent capability of accelerating the healing process of both acute and chronic wounds. The skin, heart, nervous system, and ophthalmic tissues are the main targets of nanoceria-based therapies, and the other soft tissues may also be evaluated in upcoming experimental studies. For the repair and regeneration of soft tissue damage and defects, nanoceria-incorporated film, hydrogel, and nanofibrous scaffolds have been proven to be highly suitable replacements with satisfactory outcomes. Still, some concerns have remained regarding the long-term effects of nanoceria administration for human tissues and organs, such as its clearance from the vital organs. Moreover, looking at the future, it seems necessary to design and develop three-dimensional (3D) printed scaffolds containing nanoceria for possible use in the concepts of personalized medicine.

Tissue engineering provides great possibilities to manage tissue damages and injuries in modern medicine. The involvement of hard biocompatible materials in tissue engineering-based therapies for the healing of soft tissue defects has impressively increased over the last few years: in this regard, different types of bioceramics were developed, examined and applied either alone or in combination with polymers to produce composites. Bioactive glasses, carbon nanostructures, and hydroxyapatite nanoparticles are among the most widely-proposed hard materials for treating a broad range of soft tissue damages, from acute and chronic skin wounds to complex injuries of nervous and cardiopulmonary systems. Although being originally developed for use in contact with bone, these substances were also shown to offer excellent key features for repair and regeneration of wounds and "delicate" structures of the body, including improved cell proliferation and differentiation, enhanced angiogenesis, and antibacterial/anti-inflammatory activities. Furthermore, when embedded in a soft matrix, these hard materials can improve the mechanical properties of the implant. They could be applied in various forms and formulations such as fine powders, granules, and micro- or nanofibers. There are some pre-clinical trials in which bioceramics are being utilized for skin wounds; however, some crucial questions should still be addressed before the extensive and safe use of bioceramics in soft tissue healing. For example, defining optimal formulations, dosages, and administration routes remain to be fixed and summarized as standard guidelines in the clinic. This review paper aims at providing a comprehensive picture of the use and potential of bioceramics in treatment, reconstruction, and preservation of soft tissues (skin, cardiovascular and pulmonary systems, peripheral nervous system, gastrointestinal tract, skeletal muscles, and ophthalmic tissues) and critically discusses their pros and cons (e.g., the risk of calcification and ectopic bone formation as well as the local and systemic toxicity) in this regard. STATEMENT OF SIGNIFICANCE: Soft tissues form a big part of the human body and play vital roles in maintaining both structure and function of various organs; however, optimal repair and regeneration of injured soft tissues (e.g., skin, peripheral nerve) still remain a grand challenge in biomedicine. Although polymers were extensively applied to restore the lost or injured soft tissues, the use of bioceramics has the potential to provides new opportunities which are still partially unexplored or at the very beginning. This reviews summarizes the state of the art of bioceramics in this field, highlighting the latest evolutions and the new horizons that can be opened by their use in the context of soft tissue engineering. Existing results and future challenges are discussed in order to provide an up-to-date contribution that is useful to both experienced scientists and early-stage researchers of the biomaterials community., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest in publishing this work., (Copyright © 2020. Published by Elsevier Ltd.)

Angiogenesis (or the development of new blood vessels) is a key event in tissue engineering and regenerative medicine; thus, a number of biomaterials have been developed and combined with stem cells and/or bioactive molecules to produce three-dimensional (3D) pro-angiogenic constructs. Among the various biomaterials, electrospun nanofibrous scaffolds offer great opportunities for pro-angiogenic approaches in tissue repair and regeneration. Nanofibers made of natural and synthetic polymers are often used to incorporate bioactive components (e.g., bioactive glasses (BGs)) and load biomolecules (e.g., vascular endothelial growth factor (VEGF)) that exert pro-angiogenic activity. Furthermore, seeding of specific types of stem cells (e.g., endothelial progenitor cells) onto nanofibrous scaffolds is considered as a valuable alternative for inducing angiogenesis. The effectiveness of these strategies has been extensively examined both in vitro and in vivo and the outcomes have shown promise in the reconstruction of hard and soft tissues (mainly bone and skin, respectively). However, the translational of electrospun scaffolds with pro-angiogenic molecules or cells is only at its beginning, requiring more research to prove their usefulness in the repair and regeneration of other highly-vascularized vital tissues and organs. This review will cover the latest progress in designing and developing pro-angiogenic electrospun nanofibers and evaluate their usefulness in a tissue engineering and regenerative medicine setting.

Biomedical waste management is getting significant consideration among treatment technologies, since insufficient management can cause danger to medicinal service specialists, patients, and their environmental conditions. The improvement of waste administration protocols, plans, and policies are surveyed, despite setting up training programs on legitimate waste administration for all healthcare service staff. Most biomedical waste substances do not degrade in the environment, and may also not be thoroughly removed through treatment processes. Therefore, the long-lasting persistence of biomedical waste can effectively have adverse impact on wildlife and human beings, as well. Hence, photocatalysis is gaining increasing attention for eradication of pollutants and for improving the safety and clearness of the environment due to its great potential as a green and eco-friendly process. In this regard, nanostructured photocatalysts, in contrast to their regular counterparts, exhibit significant attributes such as non-toxicity, low cost and higher absorption efficiency in a wider range of the solar spectrum, making them the best candidate to employ for photodegradation. Due to these unique properties of nanophotocatalysts for biomedical waste management, we aim to critically evaluate various aspects of these materials in the present review and highlight their importance in healthcare service settings.

Angiogenesis plays a critical role within the human body, from the early stages of life (i.e., embryonic development) to life-threatening diseases (e.g., cancer, heart attack, stroke, wound healing). Many pharmaceutical companies have expended huge efforts on both stimulation and inhibition of angiogenesis. During the last decade, the nanotechnology revolution has made a great impact in medicine, and regulatory approvals are starting to be achieved for nanomedicines to treat a wide range of diseases. Angiogenesis therapies involve the inhibition of angiogenesis in oncology and ophthalmology, and stimulation of angiogenesis in wound healing and tissue engineering. This review aims to summarize nanotechnology-based strategies that have been explored in the broad area of angiogenesis. Lipid-based, carbon-based and polymeric nanoparticles, and a wide range of inorganic and metallic nanoparticles are covered in detail. Theranostic and imaging approaches can be facilitated by nanoparticles. Many preparations have been reported to have a bimodal effect where they stimulate angiogenesis at low dose and inhibit it at higher doses.

Natupolymer-based scaffolds can increase cell affinity to biomaterials and improve cell responses. Silk fibroin, chitosan and gelatin that mimic the properties of natural extra-cellular matrix (ECM) were chosen due to their biocompatibility, biodegradability and less immunogenic reactions. We prepared composite scaffolds with different blending ratios of silk fibroin-chitosan-gelatin by freeze-drying technique. Silk fibroin was extracted from the Bombyx mori silkworm. The scaffolds were characterized by scanning electron microscopy (SEM), surface wettability, swelling measurements, In Vitro enzymatic degradation measurements and tensile test. The composite scaffolds showed pore sizes from 125 μm to 175 μm, good interconnectivity between pores and suitable porosity which are desirable for cell growth. The addition of chitosan-gelatin to silk fibroin increased water uptake and degradation rate and reduced mechanical strength but silk fibroin affect reversely on the degradation and mechanical strength of composite scaffolds. Biocompatibility of scaffolds was demonstrated by MTT-assay and hematoxylin-eosin (H&E) staining which lead to the growth and adhesion of endothelial cells. In this study, the fabricated composite scaffolds have the potential for tissue engineering applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Therapeutic advancements in the treatment of various ocular diseases is often linked to the development of efficient drug delivery systems (DDSs), which would allow a sustained release while maintaining therapeutic drug levels in the target tissues. In this way, ocular tissue/cell response can be properly modulated and designed in order to produce a therapeutic effect. An ideal ocular DDS should encapsulate and release the appropriate drug concentration to the target tissue (therapeutic but non-toxic level) while preserving drug functionality. Furthermore, a constant release is usually preferred, keeping the initial burst to a minimum. Different materials are used, modified, and combined in order to achieve a sustained drug release in both the anterior and posterior segments of the eye. After giving a picture of the different strategies adopted for ocular drug release, this review article provides an overview of the biomaterials that are used as drug carriers in the eye, including micro- and nanospheres, liposomes, hydrogels, and multi-material implants; the advantages and limitations of these DDSs are discussed in reference to the major ocular applications.

The purpose of this study was to describe the distinct regional distribution patterns of expression of the α7 and α4 subunits of nicotinic acetylcholine receptors (nAChRs) and their left-right lateralisation in the rat hippocampus during the first 2 weeks of postnatal (P) development. Eighteen male pups were randomly divided into three groups: P0, P7, and P14. After removing the newborn brains, real-time polymerase chain reaction, western blot, and immunohistochemistry techniques were used to evaluate expression of the receptors. Results indicated that the expression profile of these receptors were time- and spatially dependent. A significant increase was observed in the distribution of α7 and α4 nAChR subunits in the developing rat hippocampus from P0 to P7 (p < .001); however, there was a significant decrease from P7 to P14 (p < .05). As a spatial effect, the highest optical density (OD) was observed in the CA3 and CA2 regions of the hippocampus, while the lowest OD was in the dentate gyrus. Moreover, the distribution of α7 and α4 nAChR subunits in the left hippocampus was significantly higher than their counterparts in the right (p < .05). From these data, the expression patterns of α7 and α4 nAChR subunits exhibited left-right asymmetry in the developing rat hippocampus., (© 2020 International Society for Developmental Neuroscience.)