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The cornea is one of the most commonly transplanted tissues worldwide. It is used to restore vision when severe visual impairment or blindness occurs in patients with corneal diseases or after trauma. Due to the global shortage of healthy donor corneas, decellularized corneal tissue has significant potential as an alternative to corneal transplantation. It preserves the native and biological ultrastructure of the cornea and, therefore, represents the most promising scaffold. This article discusses different methods of corneal decellularization based on the current literature. We searched PubMed.gov for articles from January 2009 to December 2023 using the following keywords: corneal decellularization, decellularization methods, and corneal transplantation. Although several methods of decellularization of corneal tissue have been reported, a universal standardised protocol of corneal decellularization has not yet been introduced. In general, a combination of decellularization methods has been used for efficient decellularization while preserving the optimal properties of the corneal tissue. [ABSTRACT FROM AUTHOR]

The development of biocompatible scaffolds is rapidly growing in several fields of human health, particularly for the treatment of bone defects. In this study, silver nanoparticle (AgNPs)-incorporated hydroxyapatite (HA), chitosan (Chi), and polyvinylpyrrolidone (PVP)-based scaffolds were fabricated using the freeze-drying method for bone tissue engineering. Physicochemical properties such as porosity, density, swelling ratio, and biodegradability, as well as blood biocompatibility, brine shrimp lethality, antibacterial activities, FTIR-ATR, tensile strength, cytotoxicity, and SEM, were conducted. A study on the in vitro release of ceftriaxone (Cef), a routinely prescribed medication for treating osteomyelitis, was done. The selected scaffolds had desirable porosity, density, swelling capability, and biodegradation rate, which would meet the basic prerequisites for osteogenesis. The scaffolds showed qualitative and quantitative antibacterial activities against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Scaffolds were minimally cytotoxic to brine shrimp and RBC biocompatible. FTIR analysis confirmed intermolecular interaction among components of scaffolds. Scaffold had a tensile strength of 2.9 ± 0.22 N/mm2 and a non-cytotoxic effect on Vero cell lines. Surface morphology, pore shape, and sizes (98–382 μm) were observed through SEM. The percentage of drug (Cef) loading was found to be 63.16 ± 4.85%. An initial burst release of Cef was 40.21 ± 1.50% in the first 24 h. A sustained release of Cef was observed after 4 days, and about 60.36 ± 2.38% was released within 14 days. Therefore, selected AgNPs-incorporated HA-Chi-PVP scaffold could be a potential aid for bone tissue engineering. [ABSTRACT FROM AUTHOR]

In addition to being a lipid-lowering medication, atorvastatin (ATV) is an anti-inflammatory agent. When there is a bone defect or inflammation of adjacent tissues, it aids in bone repair. This study aimed to develop a chitosan–alginate (CS/ALG)–tripolyphosphate (TPP)–ATV hybrid hydrogel as a drug delivery system, using a tissue engineering scaffold for the first time. For this purpose, a CS/ALG hydrogel crosslinked with TPP was developed. The delivery profile of ATV and its physicochemical properties such as particle size and hydrogel swelling percentage were determined. The structure and morphology of the hydrogels were analyzed using Fourier transform infrared spectroscopy and scanning electron microscopy. As a result, an alginate–chitosan hydrogel with a TPP crosslinker was prepared. The results revealed that drug loading was nearly complete, and the first hour revealed a 25% explosive release. The drug was gradually released over 10 hr at approximately 35%. The amount of crosslinker used significantly influenced the encapsulation gain and release profiles. Owing to its high porosity and swelling, the CS/ALG hydrogel crosslinked with PPT is an ideal scaffold for loading drugs, macromolecules, and cells. [ABSTRACT FROM AUTHOR]

Biomaterials are feasible resources that aids to replace damaged structures in our bodies. The most biologically active flora is Aloe vera which has many bioactive compounds that are anti-inflammatory, antimicrobial, and have ECM mimicking protein content which helps in the healing of wounds and also acts as an ECM factor for stem cell homing and differentiation. The Aloe vera containing 10 w / v of gelatin was lyophilized. Scaffolds had sharper morphology, greater hydrophilic properties, and a Young's modulus of 6.28 MPa and 15.9 MPa of higher tensile strength are desirable. In tissue engineering and regenerative medicine, biologically active scaffolds have been producing hopeful outcomes in both restoration and replacement, respectively. The objective of the present investigation is to test the idea that incorporating gelatin to Aloe vera scaffolds might enhance their structure, good biocompatibility, and possibly even bioactivity. The SEM picture of the composite scaffold revealed pore walls. The scaffolds had linked pores with diameters ranging from 93 to 296 μm. Aloe vera and the matrix interact well, according to the FTIR study, which could lead to a reduction in the amount of water-binding sites and a reduction in the material's ability to absorb water. Aloe vera with 10% gelatin (AV/G) scaffold was investigated for different biological reactions of human gingival tissue mesenchymal stem cells (MSCs) in terms of cell proliferation, morphology, and cell migration. The results demonstrated the potential of the AV/G scaffold as a biomaterial that offers new insight in the field of tissue engineering. [ABSTRACT FROM AUTHOR]

Stem cell therapy has emerged as the most vibrant area of research, due to the capacity of stem cells for self-renewal and differentiation into different types of cell lines upon their culture. But lately, scientists become increasingly aware of the limitations of conventional 2D culture and stem cell culture media, due to several key drawbacks associated with this model, such as immune response upon transplantation, animal pathogen contamination, and complication, during developmental studies due to undefined factors in the cultural media. In this study, an attempt has been made to develop a new type of polymeric 3D scaffold based on the self-assembly of a star-like amphiphilic copolymer of poly(caprolactone)–poly(ethylene oxide) unit into nanowires (nanofibers), that have a scale similar to the native extracellular matrix and are capable of mimicking the extracellular microenvironment where the functional properties of stem cells can be observed and manipulated. The obtained data showed that polymeric-based nanofibers can be used as a 3D scaffold for mouse embryonic stem cells (mESCs) growth without losing their stem cell phenotype. The results obtained suggest that the polymeric 3D scaffolds (nanofibers) not only support stem cells' growth and proliferation but also preserve the mESC pluripotency. [ABSTRACT FROM AUTHOR]

One promising treatment for degenerative retinal diseases such as age-related macular degeneration (AMD) is the delivery of retinal pigment epithelial (RPE) cells using degradable scaffolds. Tough-aligned scaffolds are promising candidates for some applications of tissue engineering, such as peripheral nerve regeneration. However, aligned scaffolds have not been investigated in retinal tissue engineering so far. Here, a comparison was made between aligned and random scaffolds fabricated from polycaprolactone (PCL) and human amniotic membrane powder (HAMP) as a scaffold for RPE cells. The effects of alignment on mechanical properties, porosity, hydrophilicity, degradation of the scaffolds, and the cellular interaction of RPE cells were investigated. The results revealed that the aligned scaffold has a lower average fiber diameter, porosity, hydrophilicity, and Young's modulus and also a higher maximum strain in failure compared with the random scaffold. However, the proliferation of RPE cells increased on the random scaffold compared to the aligned scaffold. Hence, the rest of the specialized cellular evaluations, such as immunohistochemistry, real-time PCR, and functional assessments were performed on random scaffolds. The seeded cells showed an expression of RPE signature genes and functionally secreted VEGF and PEDF. Therefore, a HAMP-based substrate was fabricated for potential use as a scaffold for RPE cell transplantation. [ABSTRACT FROM AUTHOR]

Millions of people around the world have bone-tissue defects. Autologous and allogeneic bone grafting are frequent therapeutic techniques; however, none has produced the best therapeutic results. This has inspired researchers to investigate novel bone-regeneration technologies. In recent years, the development of bone tissue engineering (BTE) scaffolds has been at the forefront of this discipline. Due to their limitless supply and lack of disease transmission, engineered bone tissue has been advanced for the repair and reconstruction of bone deformities. Bone tissue is a highly vascularized, dynamic tissue that constantly remodels during an individual's lifetime. Bone tissue engineering is aimed at stimulating the creation of new, functional bone by combining biomaterials, cells, and factor treatment synergistically. This article provides a review of wollastonite's biomaterial application in bone tissue engineering. This work includes an explanation of wollastonite minerals including mining, raw materials for the synthesis of artificial wollastonite with various methods, its biocompatibility, and biomedical applications. Future perspectives are also addressed, along with topics like bone tissue engineering, the qualities optimal bone scaffolds must have, and the way a scaffold is designed can have a big impact on how the body reacts. [ABSTRACT FROM AUTHOR]

Due to their particular water absorption capacity, hydrogels are the most widely used scaffolds in biomedical studies to regenerate damaged tissue. Hydrogels can be used in tissue engineering to design scaffolds for three-dimensional cell culture, providing a novel alternative to the traditional two-dimensional cell culture as hydrogels have a three-dimensional biomimetic structure. This material property is crucial in regenerative medicine, especially for the nervous system, since it is a highly complex and delicate structure. Hydrogels can move quickly within the human body without physically disturbing the environment and possess essential biocompatible properties, as well as the ability to form a mimetic scaffold in situ. Therefore, hydrogels are perfect candidates for biomedical applications. Hydrogels represent a potential alternative to regenerating tissue lost after removing a brain tumor and/or brain injuries. This reason presents them as an exciting alternative to highly complex human physiological problems, such as injuries to the central nervous system and neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Background. The microenvironment of bone defects displayed that M2 polarization of macrophagocyte could promote the osteoblast growth and benefit the wound healing. Bone scaffold transplantation is considered to be one of the most promising methods for repairing bone defects. The present research was aimed at constructing a kind of novel bone scaffold nanomaterial of MSN@IL-4 for treating bone defects responding to the wound microenvironment of bone defects and elucidating the mechanics of MSN@IL-4 treating bone defect via controlling release of IL-4, inducing M2 polarization and active factor release of macrophagocyte, and eventually relieving osteoblast injury. Methods. MSN@IL-4 was firstly fabricated and its release of IL-4 was assessed in vitro. Following, the effects of MSN@IL-4 nanocomplex on the release of active factors of macrophage were examined using Elisa assay and promoting M2 polarization of the macrophage by immunofluorescence staining. And then, the effects of active factors from macrophage supernatant induced by MSN@IL-4 on osteoblast growth were examined by CCK-8, flow cytometry, and western blot assay. Results. The release curve of IL-4 in vitro displayed that there was more than 80% release ratio for 30th day with a sustained manner in pH 5.5. Elisa assay data showed that MSN@IL-4 nanocomplex could constantly promote the release of proproliferative cytokine IL-10, SDF-1α, and BMP-2 in macrophagocyte compared to only IL-4 treatment, and immunofluorescent image showed that MSN@IL-4 could promote M2 polarization of macrophagocytes via inducing CD206 expression and suppressing CD86 expression. Osteoblast injury data showed that the supernatant from macrophagocyte treated by MSN@IL-4 could promote the osteoblast proliferation by MTT assay. Flow cytometry data showed that the supernatant from macrophagocyte treated by MSN@IL-4 could suppress the osteoblast apoptosis from 22.1% to 14.6%, and apoptosis-related protein expression data showed that the supernatant from macrophagocyte treated by MSN@IL-4 could suppress the expression of Bax, cleaved caspase 3, and cleaved caspase 8. Furthermore, the immunofluorescent image showed that the supernatant from macrophagocyte treated by MSN@IL-4 could inhibit nucleus location of p65, and western blot data showed that the supernatant from macrophagocyte treated by MSN@IL-4 could suppress the phosphorylation of IKK and induce the expression of IκB. Conclusion. MSN@IL-4 could control the sustaining release of IL-4, and it exerts the protective effect on osteoblast injury via inducing M2 polarization and proproliferative cytokine of macrophagocyte and following inhibiting the apoptosis and NF-κB pathway-associated inflammation of osteoblast. [ABSTRACT FROM AUTHOR]

The effect of titanium scaffold geometry on the bone regeneration ability of the scaffold remains unclear. Here, selective laser melting as a 3D printing technology was used to create porous titanium alloy scaffolds with two unit structures: a hollow hexagonal prism (group A) and a hollow triangular prism (group B). The structures and morphologies of the scaffolds were characterized before mechanical properties were simulated. Cell adhesion behaviors, osteoblast activity and proliferation, and alkaline phosphatase (ALP) activity were evaluated, in addition to in vivo testing in an animal model. The results showed that the two scaffolds made of Ti6Al4V had compression moduli similar to that of human cortical bone (116.91 ± 0.01 and 174.29 ± 2.21 MPa vs. 89–164 MPa). The two scaffolds were nontoxic to cells and had good biocompatibility, while group A scaffolds facilitated cell adhesion. The number of cells increased gradually in culture. The ALP activity of cells on group A scaffolds demonstrated higher osteogenic ability than that of group B scaffolds. The in vivo tests showed that all scaffolds retained their shape well after implantation, and no obvious inflammatory reaction or infection in surrounding tissues was found. Based on fluorescence staining, mature new bone formation was found at week 12. Group A scaffolds showed better bone integration ability compared with group B scaffolds. The percentage of new bone area in group A (7.5%) was higher than that in group B (6.5%). This research suggests that the hollow hexagonal prism structure of porous scaffolds can promote osteogenic differentiation and osseointegration better than the triangular prism structure. [ABSTRACT FROM AUTHOR]

Geotechnical engineering is a new technical system established by European and American countries in the practice of civil engineering in the 1960s. There are many methods to manufacture nanofibers, such as stretching, template synthesis, self-assembly, microphase separation, and electrospinning. Among them, electrospinning is widely used because of its simple operation, wide application range, and relatively high production efficiency. This paper aims to study how to analyze and study the properties of engineering scaffolds along the way based on nanofiber polymers. In this paper, the performance of geotechnical scaffolds is proposed, which is based on nanofibers. This paper focuses on the concept of nanofibers and geotechnical physical mechanics. In this paper, the performance of geotechnical support is designed and analyzed. The experimental results show that the initial thermal decomposition temperature of the pure SF collagen nanofiber membrane is about 250°C and that of the pure PLLA nanofiber membrane is about 330°C. When SF collagen/PLLA = 70 : 30, the initial thermal decomposition temperature of the material is about 260°C. When the mass ratio is 50 : 50, the initial thermal decomposition temperature increases to about 270°C. When the mass ratio is 30 : 70, the initial thermal decomposition temperature increases to about 280°C. This is because PLLA is a semi-crystalline polymer with certain thermal stability. Its heat resistance is better than that of pure SF collagen. With the increase in the amount of PLLA, it can effectively improve the thermal stability of blended composite nanofiber scaffolds. [ABSTRACT FROM AUTHOR]

A nanoscaffold is a porous scaffold. It injects antibiotics, cells, and polymer particles into damaged cavities in the form of injectables and forms hydrogels after the molecules self-assemble at the injection site. Sports rehabilitation is a new frontier field integrating sports, health, and medicine, also known as physical therapy. It is the use of various sports methods for the injured or disabled, so that they can fully recover their physical functions and spirits, and can make them reintegrate into society. It mainly studies the relationship between sports and health. Among the tissue engineering scaffolds used as seed cell carriers, nanomaterials are playing an increasingly important role in the study of joint injury and repair due to their unique effects such as cell adhesion and proliferation. The purpose of this paper is to study a reliable nanoscaffold material for the treatment of patients with hip injuries in athletes and to observe its actual effect in combination with sports rehabilitation therapy. In this paper, an electrospinning method was proposed to prepare nanoscaffold materials, and the nanoscaffold materials were applied to the exercise rehabilitation process of two groups of hip patients, and the data of the patients' rehabilitation were calculated. The results showed that the OD value of the cells in the exercise rehabilitation therapy using nanofiber scaffolds increased significantly, and the average daily growth rate of the OD value was 0.112. And the rehabilitation after 5 months was 19.8 points higher in hip range of motion score, 11.3 points higher in overall function score, and 6.2% lower in complication rate compared with ordinary exercise rehabilitation therapy. Therefore, it can be concluded that the therapy of the nanofiber scaffold material combined with exercise rehabilitation can more efficiently help patients with hip joint injury to recover, and the probability of complications is lower compared with the traditional exercise rehabilitation therapy. [ABSTRACT FROM AUTHOR]

Sports ligament injury refers to muscle or joint injury caused by excessive use of limbs or long-term use of wrong training methods. This is a very common sports disease, and the body's ability to heal itself is poor. At present, the clinical methods to treat this disease mainly include autologous structure transplantation, allogeneic structure transplantation, and artificial ligament reconstruction. Nanomaterials refer to materials made of them as basic units. Transplantation of homologous and allogeneic structures may cause immune rejection in the human body. Therefore, the use of nanomaterials to reconstruct artificial ligaments is the current research hotspot of sports injury repair. This article mainly studies the repair effect of nanomaterials on basketball sports ligament injuries. In this paper, by implanting nanofiber scaffolds in sports-injured rabbits, observing and comparing the healing, growth, and proliferation of damaged cells after implantation, and the compatibility of nanofibers with cell tissues, so as to determine that nanomaterials have an impact of lion sports injury repair and the interaction between nanomaterials and cells. According to the experimental results, the implantation of nanofiber scaffolds can greatly accelerate cell proliferation and differentiation and promote the healing of sports-damaged tissues; nanofiber scaffolds have good histocompatibility, so the use of nanomaterials can promote the repair of sports ligament injury in basketball sports. [ABSTRACT FROM AUTHOR]

An appropriate and reliable sterilization technique is crucial for tissue engineering scaffolds. Skeletal muscle scaffolds are often fabricated using microfilaments of a wide variety of polymers. One method for sterilization is 25 kGy of gamma irradiation. In addition, sterilization through irradiation should administer a dose within a specific range. Radiation directly affects the chemical and mechanical properties of scaffolds. The accuracy and effects of irradiation are often not considered during sterilization procedures; however, these are important since they provide insight on whether the sterilization procedure is reliable and reproducible. This study focused on the chemical and mechanical characterization of 25 kGy gamma-irradiated scaffold. The accuracy and uncertainty of the irradiation procedure were also obtained. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses were performed to determine whether the crystallinity of the polymer changed after irradiation and whether gamma rays influenced its thermal properties. The tensile parameters of the microfilaments were analyzed by comparing irradiated and nonirradiated scaffolds to determine whether gamma radiation changed their elastic behavior. Dose distribution and uncertainty were recorded with several dosimeters. The results showed that the irradiation process slightly affected the mechanical parameters of the scaffold; however, it did not modify its crystallinity or thermal properties. The irradiation was uniform, since the measured uncertainty was low. The scaffold was pathogen-free after 7 days; this meant sterilization was achieved. These results indicated that gamma-sterilized scaffolds were a promising material for use as a skeletal muscle analog material for tissue-engineering applications because they can be sterilized with gamma rays without changing their chemical structure and mechanical properties. This study provided the dose distribution measurement and uncertainty calculations for the sterilization procedure. [ABSTRACT FROM AUTHOR]

Development of large, clinically sized tissue constructs with efficient mass transport is a tremendous need in tissue engineering. One major challenge in large tissue-engineered constructs is to support homogeneous delivery of oxygen and nutrients throughout the tissue scaffold while eliminating induced hypoxic regions in depth. To address this goal, we introduced an especial channeled architecture on porous silk-based tissue scaffolds to improve supplying of oxygen to the cells in central regions of the scaffolds. Oxygen gradients were measured and evaluated in three scaffold prototypes, namely, one unchanneled and two channeled scaffolds with different channel diameters (500 μm and 1000 μm). The channels were introduced into the constructs using stainless-steel rods arranged uniformly in stainless-steel mold, a fabrication method that enables precise control over channel diameter and the distance between channels. During 2-week culture of G292 cells, the 1000 μm channeled scaffolds demonstrated higher oxygen concentration at the center compared to 500 μm channeled prototype; however, the oxygen concentration approached the same level around the last days of culture. Nevertheless, homogenous oxygen distribution throughout the 1000 μm channeled constructs and the consequence of higher cell proliferation at day 14 postseeding corroborate the efficient elimination of induced hypoxic regions; and therefore, it holds promise for clinically relevant sized scaffold especially in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Introduction. Chitosan is a natural biopolymer that attracted enormous attention in biomedical fields. The main components of regenerative endodontic procedures (REPs), as well as tissue engineering, are scaffolds, stem cells, and growth factors. As one of the basic factors in the REPs is maintaining vascularization, this study was aimed at developing basic fibroblast growth factor- (bFGF-) loaded scaffolds and investigating their effects on the angiogenic induction in human dental pulp stem cells (hDPSCs). Methods. Poly (ε-caprolactone) (PCL)/chitosan- (CS-) based highly porous scaffold (PCL/CS) was prepared and evaluated by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) analyses. The adhesion and survival potency of seeded cells were assessed by SEM and MTT assays, respectively. The amount of angiogenic markers was investigated in gene and protein levels by real-time PCR and western blotting assays, respectively. Results. Based on our findings, the SEM and FTIR tests confirmed the appropriate structure of synthesized scaffolds. Besides, the adhesion and survival rate of cells and the levels of VEGFR-2, Tie2, and Angiopoietin-1 genes were increased significantly in the PCL/CS/bFGF group. Also, the western blotting results showed the upregulation of these markers at protein levels, which were considerably higher at the PCL/CS/bFGF group (P < 0.05). Conclusions. On a more general note, this study demonstrates that the bFGF-loaded PCL/CS scaffolds have the potential to promote angiogenesis of hDPSCs, which could provide vitality of dentin-pulp complex as the initial required factor for regenerative endodontic procedures. [ABSTRACT FROM AUTHOR]

In the last decades, cell-based approaches for bone tissue engineering (BTE) have relied on using models that cannot replicate the complexity of the bone microenvironment. There is an ongoing amount of research on scaffold development responding to the need for feasible materials that can mimic the bone extracellular matrix (ECM) and aid bone tissue regeneration (BTR). In this work, a porous cellulose acetate (CA) fiber mat was developed using the electrospinning technique and the mats were chemically modified to bioactivate their surface and promote osteoconduction and osteoinduction. The mats were characterized using FTIR and SEM/EDS to validate the chemical modifications and assess their structural integrity. By coupling adhesive peptides KRSR, RGD, and growth factor BMP-2, the fiber mats were bioactivated, and their induced biological responses were evaluated by employing immunocytochemical (ICC) techniques to study the adhesion, proliferation, and differentiation of premature osteoblast cells (hFOB 1.19). The biological assessment revealed that at short culturing periods of 48 hours and 7 days, the presence of the peptides was significant for proliferation and adhesion, whereas at longer culture times of 14 days, it had no significant effect on differentiation and maturation of the osteogenic progenitor cells. Based on the obtained results, it is thus concluded that the CA porous fiber mats provide a promising surface morphology that is both biocompatible and can be rendered bioactive upon the addition of osteogenic peptides to favor osteoconduction leading to new tissue formation. [ABSTRACT FROM AUTHOR]

Montmorillonite (MMT) has attracted widespread attention in the field of bone tissue engineering in recent years because of its interlayer domain structure. The progress of MMT application was reviewed in this article. Concretely, the application of MMT was mainly explained from the structural characteristics, mechanical strengthening mechanism, organic functionalization, and drug loading and release. Firstly, the polar polymer molecular chains are easily induced into the interlayer domain of MMT to form an interlock and achieve the mechanical strengthening of scaffold. Secondly, the "sandwich" sheet structure of MMT can be exfoliated into graphene-like MMT nanosheets, providing a nanostrengthening effect for polymer matrix. In addition, MMT's interlayer domain provides a favorable environment for the loading and slow release of drugs, and it is an ideal platform for the functionalization of bone scaffolds. More importantly, MMT can be easily modified by cation exchange and chemical reaction to further improve the compatibility of composites: such as strengthening mechanical interlocking and nanostrengthening effects and achieving controllable loading and release of drugs. It is expected to provide a reference for improving the application of bone tissue engineering scaffolds. [ABSTRACT FROM AUTHOR]

Electrospinning has become a popular nanotechnology for the fabrication of tissue engineering scaffolds, which can precisely regulate fiber diameter and microstructure. Herein, we have prepared a three-dimensional polyacrylonitrile (PAN) nanofiber by liquid-assisted electrospinning. The spacing between PAN nanofibers can reach to 15-20 μm, as the uniform internally connected pore structure can be formed, through the regulation of parameters. Furthermore, the chitosan attached to the as-prepared nanofibers gives the material antibacterial effect and increases its biocompatibility. Meanwhile, the special structure of chitosan also provides the possibility for further loading drugs in dressings in the future. This newly developed nanocomposite seems to be highly suitable for wound healing due to its unique properties of biodegradability, biocompatibility, and antimicrobial effectiveness. [ABSTRACT FROM AUTHOR]

Animal models play an important role in preclinical studies, especially in tissue engineering scaffolds for cartilage repair, which require large animal models to verify the safety and effectiveness for clinical use. The small ruminant models are most widely used in this field than other large animals because they are cost-effective, easy to raise, not to mention the fact that the aforementioned animal presents similar anatomical features to that of humans. This review discusses the experimental study of tissue engineering scaffolds for knee articular cartilage regeneration in small ruminant models. Firstly, the selection of these scaffold materials and the preparation process in vitro that have been already used in vivo are briefly reviewed. Moreover, the major factors influencing the rational design and the implementation as well as advantages and limitations of small ruminants are also demonstrated. As regards methodology, this paper applies principles and methods followed by most researchers in the process of experimental design and operation of this kind. By summarizing and comparing different therapeutic concepts, this paper offers suggestions aiming to increase the effectiveness of preclinical research using small ruminant models and improve the process of developing corresponding therapies. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) bioprinting is a revolutionary technology that replicates 3D functional living tissue scaffolds in vitro by controlling the layer-by-layer deposition of biomaterials and enables highly precise positioning of cells. With the development of this technology, more advanced research on the mechanisms of tissue morphogenesis, clinical drug screening, and organ regeneration may be pursued. Because of their self-renewal characteristics and multidirectional differentiation potential, induced pluripotent stem cells (iPSCs) have outstanding advantages in stem cell research and applications. In this review, we discuss the advantages of different bioinks containing human iPSCs that are fabricated by using 3D bioprinting. In particular, we focus on the ability of these bioinks to support iPSCs and promote their proliferation and differentiation. In addition, we summarize the applications of 3D bioprinting with iPSC-containing bioinks and put forward new views on the current research status. [ABSTRACT FROM AUTHOR]

Silk porous scaffold possesses 3D space structure for cell adhesion and tissue growth and demonstrates promising applications in biomedical engineering. In this study, a porous silk scaffold was prepared from formic acid, and its morphology, structure, mechanical properties, and biocompatibility were characterized. The preparation process involved silk dissolution in formic acid and salt leaching in water, avoiding widely used organic solvent-induced crystallization including methanol or ethanol. The resulting porous silk scaffolds showed good pore structure, stable silk II crystalline structure, good mechanical properties, and enhanced cell biocompatibility. Therefore, these findings demonstrate that porous silk scaffold derived from formic acid has great potential applications as 3D scaffold for cell culture and tissue repair. [ABSTRACT FROM AUTHOR]

With the continued development of sports in China, sports sometimes cause cartilage damage. The purpose of this research is to study the tissue engineering scaffold material for sports cartilage damage repair. In this study, mesenchymal rat bone marrow stem cells (to put it simply, stem cells are a type of cell with unlimited or immortal self-renewal capacity, capable of producing at least one type of highly differentiated progeny cells) were obtained by the total bone wash method. The cells were inoculated into the cell culture bottle. When the primary cultured cells proliferated to about 80% of the culture bottle area, the cells were digested with trypsin to open the cell link, then the medium containing 10% serum was added to terminate the cell digestion, and then the passage expansion was carried out according to the cell density. PLGA/NHA and PLGA were heated to 65°C under ultrasonic vibration until uniform PLGA/NHA and PLGA solutions were obtained. Then, the samples were added to the tube mold and then heated and cooled to obtain the composite porous scaffold of mesenchymal stem cells. 10 μl MSCs cell suspension was extracted with a microinjector, and the needle was injected from the inside of the scaffold, and the cell suspension was added outside the scaffold to ensure that there were composite cells inside and outside the scaffold. The subcutaneous tissue of the skin was cut along the medial side of the knee joint and the capsule of the switch segment was cut. The scaffold materials were filled into the osteochondral defect to observe the cartilage healing. The mechanical strength of 0.5% PLGA-MSCs composite porous scaffold was increased to 1.1 MPa, and the cell density was high. The repair of cartilage in rats was the best. The results showed that the porous scaffolds designed in this study have good compatibility and are beneficial to repair sports cartilage injury. [ABSTRACT FROM AUTHOR]

Electrospun nanofibers have been frequently used for tissue engineering due to their morphological similarities with the extracellular matrix (ECM) and tunable chemical and physical properties for regulating cell behaviors and functions. However, most of the existing electrospun nanofibers have a closely packed two-dimensional (2D) membrane with the intrinsic shortcomings of limited cellular infiltration, restricted nutrition diffusion, and unsatisfied thickness. Three-dimensional (3D) electrospun nanofiber-based scaffolds can provide stem cells with 3D microenvironments and biomimetic fibrous structures. Thus, they have been demonstrated to be good candidates for in vivo repair of different tissues. This review summarizes the recent developments in 3D electrospun nanofiber-based scaffolds (ENF-S) for tissue engineering. Three types of 3D ENF-S fabricated using different approaches classified into electrospun nanofiber 3D scaffolds, electrospun nanofiber/hydrogel composite 3D scaffolds, and electrospun nanofiber/porous matrix composite 3D scaffolds are discussed. New functions for these 3D ENF-S and properties, such as facilitated cell infiltration, 3D fibrous architecture, enhanced mechanical properties, and tunable degradability, meeting the requirements of tissue engineering scaffolds were discovered. The applications of 3D ENF-S in cartilage, bone, tendon, ligament, skeletal muscle, nerve, and cardiac tissue regeneration are then presented with a discussion of current challenges and future directions. Finally, we give summaries and future perspectives of 3D ENF-S in tissue engineering and clinical transformation. [ABSTRACT FROM AUTHOR]

The current review aims to systematically assess the osteogenic capacity of gingiva-derived mesenchymal stem cells (GMSCs) in preclinical studies. A comprehensive electronic search of PubMed, Embase, Web of Science, and Scopus databases, as well as a manual search of relevant references, was performed in June 2020 without date or language restrictions. Eligibility criteria were the following: studies that compared mesenchymal stem cells (MSCs) derived from the gingiva with other MSC sources (in vitro or in vivo) or cell-free scaffold (in vivo) and studies that reported at least one of the following outcomes: osteogenic potential and new bone formation for in vitro and in vivo, respectively. Moreover, the assessment of included studies was conducted using appropriate guidelines. From 646 initial retrieved studies, 35 full-text articles were subjected to further screening and 26 studies were selected (20 in vitro studies and 6 in vivo studies). GMSCs showed great proliferation capacity and expressed recognized mesenchymal stem cell markers, particularly CD90. In vitro, MSC sources including GMSCs were capable of undergoing osteogenic differentiation with less ability in GMSCs, while most in vivo studies confirmed the capacity of GMSCs to regenerate bony defects. Concerning the assessment of methodological quality, in vitro studies met the relevant guideline except in five areas: the sample size calculation, randomization, allocation concealment, implementation, and blinding, and in vivo publications had probably low risk of bias in most domains except in three areas: allocation concealment, attrition, and blinding items. [ABSTRACT FROM AUTHOR]

Tissue decellularization has rapidly developed to be a practical approach in tissue engineering research; biological tissue is cleared of cells resulting in a protein-rich husk as a natural scaffold for growing transplanted cells as a donor organ therapy. Minimally processed, acellular extracellular matrix reproduces natural interactions with cells in vitro and for tissue engineering applications in animal models. There are many decellularization techniques that achieve preservation of molecular profile (proteins and sugars), microstructure features such as organization of ECM layers (interstitial matrix and basement membrane) and organ level macrofeatures (vasculature and tissue compartments). While structural and molecular cues receive attention, mechanical and material properties of decellularized tissues are not often discussed. The effects of decellularization on an organ depend on the tissue properties, clearing mechanism, chemical interactions, solubility, temperature, and treatment duration. Physical characterization by a few labs including work from the authors provides evidence that decellularization protocols should be tailored to specific research questions. Physical characterization beyond histology and immunohistochemistry of the decellularized matrix (dECM) extends evaluation of retained functional features of the original tissue. We direct our attention to current technologies that can be employed for structure function analysis of dECM using underutilized tools such as atomic force microscopy (AFM), cryogenic electron microscopy (cryo-EM), dynamic mechanical analysis (DMA), Fourier-transform infrared spectroscopy (FTIR), mass spectrometry, and rheometry. Structural imaging and mechanical functional testing combined with high-throughput molecular analyses opens a new approach for a deeper appreciation of how cellular behavior is influenced by the isolated microenvironment (specifically dECM). Additionally, the impact of these features with different decellularization techniques and generation of synthetic material scaffolds with desired attributes are informed. Ultimately, this mechanical profiling provides a new dimension to our understanding of decellularized matrix and its role in new applications. [ABSTRACT FROM AUTHOR]

β-Tricalcium phosphate (TCP) is a type of bioceramic material which is commonly used for hard tissue repair and famous of its remarkable biocompatibility and osteoconductivity with similar composition to natural bone. However, TCP lacks osteoindcutive properties. Stromal-derived factor 1α (SDF-1α) can promote bone regeneration with excellent osteoinduction effect. In this study, SDF-1α was loaded into TCP to investigate the in vitro effects of SDF-1α on the osteoinductive properties of TCP. In vitro studies showed that SDF-1α/TCP scaffold significantly stimulated the expression of osteopontin and osteocalcin. As to the in vivo studies, the rabbit bone defect model showed that SDF-1α stimulated more new bone formation. In conclusion, SDF-1α/TCP bioceramic scaffolds could further promote bone regeneration compared to pure TCP bioceramics. [ABSTRACT FROM AUTHOR]

This study explored the effects of a silk fibroin-RGD-stem cell factor (SF-RGD-SCF) scaffold on the migration, proliferation, and attachment of stem cells of apical papilla (SCAPs). SF, SF-RGD, SF-SCF, and SF-RGD-SCF scaffolds were prepared, and laser confocal microscopy was used to observe the adhesion and growth status of SCAPs on the scaffolds. Furthermore, the numbers of SCAPs on the scaffolds were counted by a digestion counting method to evaluate their proliferation. Cells on the SF-RGD-SCF scaffold proliferated more than those on the other scaffolds and showed a more obvious tendency to migrate to the scaffold's deep porous structure after 7 d seeding. Live/dead cell staining results showed that almost all the adhered cells were alive after 7 d. Furthermore, cell counting showed that the number of cells on the SF-RGD-SCF scaffold was highest after both 1 and 7 d (P < 0.05). Thus, the SF-RGD-SCF composite is biocompatible and promotes the migration, adhesion, and proliferation of SCAPs, making it of potential use as a scaffold for cell-homing pulp regeneration. [ABSTRACT FROM AUTHOR]

β-Tricalcium phosphate (TCP) is a type of bioceramic material which is commonly used for hard tissue repair and famous of its remarkable biocompatibility and osteoconductivity with similar composition to natural bone. However, TCP lacks osteoindcutive properties. Stromal-derived factor 1α (SDF-1α) can promote bone regeneration with excellent osteoinduction effect. In this study, SDF-1α was loaded into TCP to investigate the in vitro effects of SDF-1α on the osteoinductive properties of TCP. In vitro studies showed that SDF-1α/TCP scaffold significantly stimulated the expression of osteopontin and osteocalcin. As to the in vivo studies, the rabbit bone defect model showed that SDF-1α stimulated more new bone formation. In conclusion, SDF-1α/TCP bioceramic scaffolds could further promote bone regeneration compared to pure TCP bioceramics. [ABSTRACT FROM AUTHOR]

Mesenchymal stemXin cells (MSCs) are a great cell source for bone regeneration. Although combining MSCs with growth factors and scaffolds provides a useful clinical strategy for bone tissue engineering, the efficiency of MSC osteogenic differentiation remains to be improved. Epigenetic modification is related to the differentiation ability of MSCs during osteogenic induction. In this study, we evaluate the effect of Chaetocin, an inhibitor of lysine-specific histone methyltransferases, on the differentiation of MSCs. We found that MSCs treated with Chaetocin demonstrated increased osteogenic ability and reduced adipogenic ability. The expression of osteogenic markers (Runx2 and OPN) was induced in MSCs by Chaetocin during osteogenic induction. Moveover, treatment of Chaetocin in MSCs improves Wnt/β-catenin signaling pathways and its downstream targets. Finally, we showed increased bone formation of MSC and Wnt/β-catenin signaling activity by treatment of Chaetocin using in vivo bone formation assays. Our data uncovered a critical role of Chaetocin in MSC osteogenic differentiation and provide new insights into bone tissue regeneration and repair. [ABSTRACT FROM AUTHOR]

Platelet aggregates, such as PRP, PRF, and CGF, have been used alone or in combination with other grafting materials to enhance restoration outcomes. The process for preparing these autografting materials requires two-step centrifugation or specific centrifuges. In this study, we obtained an injectable fibrin scaffold (IFS) rich in growth factors by one-step centrifugation of whole blood from rabbits. The purpose of this study is to introduce some characteristics of IFS. This scaffold was characterized using various techniques, including Masson's trichrome staining, scanning electron microscopy, porosity measurements, and cell counting. The sustained release of growth factors, including PDGF, VEGF, TGF-β1, IGF, FGF, and EGF, was quantified using ELISA assay. The obtained IFS was tested for its effects on cell proliferation, extracellular matrix deposition, and full-thickness skin defect repair. The prepared IFS is characterized by a loose fibrin network structure with white blood cells and platelets that slowly release growth factors and can promote the healing of skin defects via the promotion of cell proliferation, collagen deposition, and tissue revascularization. In addition, its liquid properties and porous structure are conducive to its application as a therapeutic component in tissue engineering. [ABSTRACT FROM AUTHOR]

For many cells used in tissue engineering applications, the scaffolds upon which they are seeded do not entirely mimic their native environment, particularly in the case of excitable tissues. For instance, muscle cells experience contraction and relaxation driven by the electrical input of an action potential. Electroactive materials can also deform in response to electrical input; however, few such materials are currently suitable as cell scaffolds. We previously described the development of poly(ethyelene glycol) diacrylate-poly(acrylic acid) as an electroactive scaffold. Although the scaffold itself supported cell growth and attachment, the voltage (20 V) required to actuate these scaffolds was cytotoxic. Here, we describe the further development of our hydrogels into scaffolds capable of actuation at voltages (5 V) that were not cytotoxic to seeded cells. This study describes the critical next steps towards the first functional electroactive tissue engineering scaffold. [ABSTRACT FROM AUTHOR]

Tissue engineering scaffolds with nanofibrous structures provide positive support for cell proliferation and differentiation in biomedical fields. These scaffolds are widely used for defective tissue repair and drug delivery. However, the degradation performance and mechanical properties of scaffolds are often unsatisfactory. Here, we successfully prepared a novel poly(3-hydroxybutyrate-4-hydroxybutyrate)/polypyrrole (P34HB-PPy) core-shell nanofiber structure scaffold with electrospinning and in situ surface polymerization technology. The obtained composite scaffold showed good mechanical properties, hydrophilicity, and thermal stability based on the universal material testing machine, contact angle measuring system, thermogravimetric analyzer, and other methods. The results of the in vitro bone marrow-derived mesenchymal stem cells (BMSCs) culture showed that the P34HB-PPy composite scaffold effectively mimicked the extracellular matrix (ECM) and exhibited good cell retention and proliferative capacity. More importantly, P34HB is a controllable degradable polyester material, and its degradation product 3-hydroxybutyric acid (3-HB) is an energy metabolite that can promote cell growth and proliferation. These results strongly support the application potential of P34HB-PPy composite scaffolds in biomedical fields, such as tissue engineering and soft tissue repair. [ABSTRACT FROM AUTHOR]

Background. The regeneration of dental pulp, especially in cases of pulp death of immature teeth, is the goal of the regenerative endodontic procedures (REPs) that are based on tissue engineering principles, consisting of stem cells, growth factors, and scaffolds. Photobiomodulation therapy (PBMT) showed to improve dental pulp regeneration through cell homing approaches in preclinical studies and has been proposed as the fourth element of tissue engineering. However, when a blood clot was used as a scaffold in one of these previous studies, only 30% of success was achieved. The authors pointed out the instability of the blood clot as the regeneration shortcoming. Then, to circumvent this problem, a new scaffold was developed to be applied with the blood clot. The hypothesis of the present study was that an experimental injectable chitosan hydrogel would facilitate the three-dimensional spatial organization of endogenous stem cells in dental pulp regeneration with no interference on the positive influence of PBMT. Methods. For the in vitro analysis, stem cells from the apical papilla (SCAPs) were characterized by flow cytometry and applied in the chitosan scaffold for evaluating adhesion, migration, and proliferation. For the in vivo analysis, the chitosan scaffold was applied in a rodent orthotopic dental pulp regeneration model under the influence of PBMT (660 nm; power output of 20 mW, beam area of 0.028 cm2, and energy density of 5 J/cm2). Results. The scaffold tested in this study allowed significantly higher viability, proliferation, and migration of SCAPs in vitro when PBMT was applied, especially with the energy density of 5 J/cm2. These results were in consonance to those of the in vivo data, where pulp-like tissue formation was observed inside the root canal. Conclusion. Chitosan hydrogel when applied with a blood clot and PBMT could in the future improve previous results of dental pulp regeneration through cell homing approaches. [ABSTRACT FROM AUTHOR]

Purpose. Our previous research has confirmed that the addition of nano-amorphous calcium phosphate (ACP) materials can improve the support of poly-L-lactic acid (PLLA) vascular scaffolds. Based on this, we continued to explore the effect of novel bioresorbable scaffold composed of PLLA and ACP nanoparticles on inflammation and calcification of surrounding tissues after scaffold implantation in porcine coronary artery. Methods. PLLA/ACP scaffolds in the experimental group and PLLA scaffolds in the control group were implanted into the coronary arteries of small pigs. Serum levels of C-reactive protein (CRP), calcium (Ca), and alkaline phosphatase (ALP) were measured before implantation and at 1, 6, 12, and 24 months after operation. Intravascular ultrasonography (IVUS) was performed to evaluate the vascular calcification score. The scaffold and surrounding tissues were hematoxylin-eosin staining for inflammation score. The scaffold and surrounding tissues were stained with NF-κB and ALP, and the positive expression index was calculated. Western blot was used to detect the expression of IL-6 and BMP-2 in the tissues around the scaffold. Results. There was no statistically significant difference between the two groups in CRP, calcium, and ALP at preimplant, 1 month, 6 months, 12 months, and 24 months (P > 0.05). The inflammation score, NF-κB positive expression index, and calcification score in the PLLA/ACP group were lower than that in the PLLA group at 12 months and 24 months (P < 0 05). The ALP positive expression index in the PLLA/ACP group was lower than that in the PLLA group at 6 months, 12 months, and 24 months (P < 0 05). Western blot results showed that the IL-6 expression level in the PLLA/ACP group was significantly lower than that in the control group at 6 months, 12 months, and 24 months (P < 0.05). The expression of BMP-2 in the PLLA/ACP group was significantly lower than that in the control group at 12 months and 24 months (P < 0.05). Conclusion. The PLLA/ACP composite scaffold has good biocompatibility. The incorporation of nanoscale ACP can reduce the inflammatory response caused by the acid metabolites of PLLA scaffolds, reduce the expression of procalcification factors in the body, and inhibit tissue calcification. The PLLA/ACP composite scaffold provides reliable guidance for the application and development of degradable vascular scaffold. [ABSTRACT FROM AUTHOR]

Supramolecular biopolymers (SBPs) are those polymeric units derived from macromolecules that can assemble with each other by noncovalent interactions. Macromolecular structures are commonly found in living systems such as proteins, DNA/RNA, and polysaccharides. Bioorganic chemistry allows the generation of sequence-specific supramolecular units like SBPs that can be tailored for novel applications in tissue engineering (TE). SBPs hold advantages over other conventional polymers previously used for TE; these materials can be easily functionalized; they are self-healing, biodegradable, stimuli-responsive, and nonimmunogenic. These characteristics are vital for the further development of current trends in TE, such as the use of pluripotent cells for organoid generation, cell-free scaffolds for tissue regeneration, patient-derived organ models, and controlled delivery systems of small molecules. In this review, we will analyse the 3 subtypes of SBPs: peptide-, nucleic acid-, and oligosaccharide-derived. Then, we will discuss the role that SBPs will be playing in TE as dynamic scaffolds, therapeutic scaffolds, and bioinks. Finally, we will describe possible outlooks of SBPs for TE. [ABSTRACT FROM AUTHOR]

The present investigation is aimed at systematically analyzing the recent literature about the innovative scaffold involved in the reconstructive surgeries by applying growth factors and tissue engineering. An extensive review of the contemporary literature was conducted according to the PRISMA guidelines by accessing the PubMed, Embase, and Scopus Elsevier databases. Authors performed the English language manuscript research published from 2003 to 2020. A total of 13 relevant studies were included in the present review. The present systematic review included only papers with significant results about correlation between scaffold, molecular features of growth factor, and reconstructive surgeries in oral maxillofacial district. The initial research with filters recorded about 1023 published papers. Beyond reading and considering of suitability, only 42 and then 36 full-text papers were recorded for the revision. All the researches recorded the possibility of using growth factors on rebuilding atrophic jaws. Different growth factors like morphogenetic factors, cytokines, and inflammatory ones and their application over different scaffold materials were recorded. Further investigations should be required in order to state scientific evidence about a clear advantage of applying tissue engineering for therapeutic purpose. [ABSTRACT FROM AUTHOR]

Functional engineered muscles are still a critical clinical issue to be addressed, although different strategies have been considered so far for the treatment of severe muscular injuries. Indeed, the regenerative capacity of skeletal muscle (SM) results inadequate for large-scale defects, and currently, SM reconstruction remains a complex and unsolved task. For this aim, tissue engineered muscles should provide a proper biomimetic extracellular matrix (ECM) alternative, characterized by an aligned/microtopographical structure and a myogenic microenvironment, in order to promote muscle regeneration. As a consequence, both materials and fabrication techniques play a key role to plan an effective therapeutic approach. Tissue-specific decellularized ECM (dECM) seems to be one of the most promising material to support muscle regeneration and repair. 3D printing technologies, on the other side, enable the fabrication of scaffolds with a fine and detailed microarchitecture and patient-specific implants with high structural complexity. To identify innovative biomimetic solutions to develop engineered muscular constructs for the treatment of SM loss, the more recent (last 5 years) reports focused on SM dECM-based scaffolds and 3D printing technologies for SM regeneration are herein reviewed. Possible design inputs for 3D printed SM dECM-based scaffolds for muscular regeneration are also suggested. [ABSTRACT FROM AUTHOR]

Fabrication of an appropriate scaffold is critical in order to recapitulate the architecture and functionality of the native tissue. In this study, we attempted to create favorable collagen fiber alignment and multilamellar with uniaxially oriented layers, using a disc collector by turning mats 90 degrees horizontally at specific times. Different concentrations of rat tail-derived type I collagen (3, 6, 8% w/v) in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) are used for electrospinning affairs. The 6% w/v collagen at an applied voltage of 20 kV and collector rotation of 2500 rpm was selected to exhibit bead-free homogeneous nanofiber with fiber thickness of 0.14 ± 0.4 µm, maximum thickness of 0.5 ± 0.08 µm, and 60% porosity. Also, scanning electron microscope images of electrospun fibers showed 3D multilamellar scaffold with the goodness of 96.5% ± 0.8 in each aligned uniaxially oriented fiber layer. Cross-linking of collagen fibers with N-(3-dimethylaminopropyl)-N0-ethylcarbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) reduced the fiber degradation rate and preserved the fiber morphology and alignment. The multilamellar mat showed significant increase in tensile strength and average breaking elongation in comparison with unilamellar mat. In vitro cell culture, using human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) on cross-linked scaffold, showed improvement in cell proliferation, attachment, migration, and intercellular junction with a flattened morphology. Raman spectra revealed the preservation of collagen structure. In addition, Raman spectra of the cell containing scaffold were the same as those of an intact intervertebral disc as a sample to be used in engineering tissues. In conclusion, our results showed that the 3D multilamellar collagen nanofibrous scaffold is more appropriate for the tissues that have multilamellar structure. [ABSTRACT FROM AUTHOR]

Introduction. In our days, several approaches reported the use of natural compounds in medical applications. Among them, pectin and allantoin are nontoxic, biocompatible, and biodegradable; however, its use for possible wound healing therapeutics is still limited. Pectin and allantoin have been applied in pharmaceutical industry and beauty cosmetic and could be also applied as scaffolds for tissue regeneration, wound healing, and so on. The aim of this study was to combine by the first time two natural ingredients to develop a new biomaterial to treat skin injuries in a rat model. Methods. For the hydrogel development, new synthesis parameters were established for the obtaining of the film such as temperature, mixing velocity and time, and drying temperatures as well. To enrich the film, the allantoin concentrations were set at 90 wt% and 100 wt% of pectin used. By in vivo assay, films were tested in wound healing in female Wistar rats, 190 ± 10 g in weight and 2 months aged. Results. The obtained films comprise 2 well-differentiated layers, one layer rich in allantoin, which will be the regenerative layer, and one rich in pectin, which will work as an antimicrobial and protective layer to the wound. These were characterized by swelling kinetics, Fourier transform of the infrared spectrum of absorption (FTIR) spectroscopy, and contact angle. The morphology and topography were determined by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). In vivo assay showed remarkable reduce in a time period in a wound healing process when the film was used. The results show that the use of PA (Pectin-Allantoin) hydrogel reduces the total healing time by 25% approximately. Conclusions. Pectin-Allantoin (PA) film has potential use in medical applications as wound healing material promoting healthy tissue renewal. [ABSTRACT FROM AUTHOR]

Introduction. The aim of this study was to investigate the ability of anti-bone morphogenetic protein 2 monoclonal antibody (anti-BMP-2 mAb) to functionalize scaffolds to mediate bone regeneration in a canine model. Materials and Methods. The mandibular right premolar 4 (PM4) was extracted in eight beagle dogs and grafted with anti-BMP-2 mAb+anorganic bovine bone mineral with 10% collagen (ABBM-C) and porcine bilayer native collagen membrane (CM). The ABBM-C and CM were functionalized with either anti-BMP-2 mAb (test group) or an isotype matched control mAb (control group). Animals were euthanized at 12 weeks for radiographic, histologic, and histomorphometric analyses. Outcomes were compared between groups. Results. 3D imaging using cone beam computed tomography (CBCT) revealed that sites treated with ABBM-C and CM functionalized with anti-BMP-2 mAb exhibited significantly more remaining bone width near the alveolar crest, as well as buccal bone height, compared with control groups. Histologic and histomorphometric analyses demonstrated that in anti-BMP-2 mAb-treated sites, total tissue volume was significantly higher in the coronal part of the alveolar bone crest compared with control sites. In anti-BMP-2 mAb-treated sites, bone formation was observed under the barrier membrane. Conclusion. Functionalization of the ABBM-C scaffold and CM appeared to have led to bone formation within healing alveolar bone sockets. [ABSTRACT FROM AUTHOR]

Studies have been directed towards the production of new titanium alloys, aiming for the replacement of Ti-6 Aluminium-4 Vanadium (TiAlV) alloy in the future. Many mechanisms related to biocompatibility and chemical characteristics have been studied in the field of implantology, but enzymatic defenses against oxidative stress remain underexplored. Bone marrow stromal cells have been explored as source of cells, which have the potential to differentiate into osteoblasts and therefore could be used as cells-based therapy. The objective of this study was to evaluate the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in porous scaffolds of Ti-6 Aluminium-4 Vanadium (TiAlV), Ti-35 Niobium (TiNb), and Ti-35 Niobium-7 Zirconium-5 Tantalum (TiNbZrTa) on mouse bone marrow stromal cells. Porous titanium alloy scaffolds were prepared by powder metallurgy. After 24 hours, cells plated on the scaffolds were analyzed by scanning electron microscopy (SEM). The antioxidant enzyme activity was measured 72 hours after cell plating. Quantitative real time PCR (qRT-PCR) was performed after 3, 7, and 14 days, and Runx2 (Runt-related transcription factor2) expression was evaluated. The SEM images showed the presence of interconnected pores and growth, adhesion, and cell spreading in the 3 scaffolds. Although differences were noted for SOD and CAT activity for all scaffolds analyzed, no statistical differences were observed (p > 0.05). The osteogenic gene Runx2 presented high expression levels for TiNbZrTa at day 7, compared to the control group (TiAlV day 3). At day 14, all scaffolds had more than 2-fold induction for Runx2 mRNA levels, with statistically significant differences compared to the control group. Even though we were not able to confirm statistically significant differences to justify the replacement of TiAlV regarding antioxidant enzymes, TiNbZrTa was able to induce faster bone formation at early time points, making it a good choice for biomedical and tissue bioengineering applications. [ABSTRACT FROM AUTHOR]

Background. Bone regeneration is a frequent research topic in clinical studies, but macroscopic studies on the clinical application of bone regeneration are rare. We conducted a bibliometric analysis, using international databases, to explore the clinical application and mechanism of bone regeneration, to highlight the relevant research hotspots and prospects. Material and Methods. Scientific reports on bone regeneration published during 2009–2019 were retrieved from PubMed. VOSviewer for cooccurrence keywords and authorship analysis. BICOMB software was used to retrieve high-frequency words and construct a text/coword matrix. The matrix was inputted into gCLUTO software, managed by biclustering analysis, in order to identify hotspots, which could achieve mountain and matrix visualizations. The matrix was also analyzed by using Ucinet 6 software for social network analysis. A strategic diagram was used for further analysis of the research hotspots of bone regeneration by "SCIMAT" software. We searched the Web of Science for relevant articles. Results. Eighty-nine high-frequency major MeSH terms were obtained from 10237 articles and were divided into 5 clusters. We generated a network visualization map, an overlay visualization mountain map, and a social network diagram. Then, the MeSH terms were subdivided into 7 categories according to each diagram; current research hotspots were identified as scaffold, drug effect, osseointegration in dental implant, guided bone regeneration, factors impacting bone regeneration, treatment of bone and tissue loss, and bone regeneration in dental implants. Conclusion. BICOMB, VOSviewer, and other bibliometric tools revealed that dental implants, scaffolds, and factors impacting bone regeneration are hot research topics, while scaffolds also hold promise from the perspective of bone tissue regeneration. [ABSTRACT FROM AUTHOR]

Introduction. Tissue engineering is an elementary necessity for several applications in the biomedical field through the use of several biopolymers derived from plants. Larrea tridentata (LT) is a very used plant for various medicinal applications with interesting properties; however, its use into cellulose hydrogels for possible regenerative therapeutics is still limited. Cellulose films could be applied in medical field as wound healing, scaffold for connective tissue for periodontal applications, and so on. The aim of this study was to evaluate the mechanical properties and in vivo and in vitro biocompatibility of cellulose hydrogels that have been enriched with LT in a rat model. Methods. By in vivo and in vitro assays, the concentration of LT was varied from 1 to 5 wt%, respectively. Hydrogel films were implanted intramuscularly into female Wistar rats, 250 g in weight and aged 2 months, to analyze their cytocompatibility and biocompatibility. Results. No case showed any evidence of inflammation or toxicity. Regarding cell morphology and adhesion, the prepared LT cellulose films had better cytocompatibility values than when polystyrene (PS) dishes were used as the control. In all cases, the results suggest that the addition of LT to the hydrogel films did not affect their cytocompatibility or biocompatibility properties and increases their clinical application due to the reported uses of LT. Conclusions. Cellulose hydrogel films enriched with LT have the potential to be used in the biomedical field acting as regenerative scaffolds. [ABSTRACT FROM AUTHOR]

Objectives. To prepare the conductive MWCNT (multiwall carbon nanotube)-agarose scaffolds with multi-microchannel for neuron growth under electrical stimulation. Methods. The scaffolds were produced by gradient freeze and lyophilization methods. The synthesized materials were characterized by SEM and near-infrared spectroscopy, and their microstructure, swelling-deswelling, conductivity, biocompatibility, and shape memory behavior were measured. A three-dimensional culture model by implanting cells into scaffolds was built, and the behaviors of RSC96 cells on scaffolds under electrical stimulation were evaluated. Results. The addition of MWCNT did not affect the pore composition ratio and shape memory of agarose scaffolds, but 0.025% wt MWCNT in scaffolds improved the swelling ratio and water retention at the swelling equilibrium state. Though MWCNTs in high concentration had slight effect on proliferation of RSC96 cells and PC12 cells, there was no difference that the expressions of neurofilament of RSC96 cells on scaffolds with MWCNTs of different concentration. RSC96 cells arranged better along the longitudinal axis of scaffolds and showed better adhesion on both 0.025% MWCNT-agarose scaffolds and 0.05% MWCNT-agarose scaffolds compared to other scaffolds. Conclusions. Agarose scaffolds with MWCNTs possessed promising applicable prospect in peripheral nerve defects. [ABSTRACT FROM AUTHOR]

Objective. Bone defects or atrophy may arise as a consequence of injury, inflammation of various etiologies, and neoplastic or traumatic processes or as a result of surgical procedures. Sometimes the regeneration process of bone loss is impaired, significantly slowed down, or does not occur, e.g., in congenital defects. For the bone defect reconstruction, a piece of the removed bone from ala of ilium or bone transplantation from a decedent is used. Replacement of the autologous or allogenic source of the bone-by-bone substitute could reduce the number of surgeries and time in the pharmacological coma during the reconstruction of the bone defect. Application of mesenchymal stem cells in the reconstruction surgery may have positive influence on tissue regeneration by secretion of angiogenic factors, recruitment of other MSCs, or differentiation into osteoblasts. Materials and Methods. Mesenchymal stem cells derived from the umbilical cord (Wharton's jelly (WJ-MSC)) were cultured in GMP-grade DMEM low glucose supplemented with heparin, 10% platelet lysate, glucose, and antibiotics. In vitro WJ-MSCs were seeded on the bone substitute Bio-Oss Collagen® and cultured in the StemPro® Osteogenesis Differentiation Kit. During the culture on the 1st, 7th, 14th, and 21st day (day in vitro (DIV)), we analyzed viability (confocal microscopy) and adhesion capability (electron microscopy) of WJ-MSC on Bio-Oss scaffolds, gene expression (qPCR), and secretion of proteins (Luminex). In vivo Bio-Oss® scaffolds with WJ-MSC were transplanted to trepanation holes in the cranium to obtain their overgrowth. The computed tomography was performed 7, 14, and 21 days after surgery to assess the regeneration. Results. The Bio-Oss® scaffold provides a favourable environment for WJ-MSC survival. WJ-MSCs in osteodifferentiation medium are able to attach and proliferate on Bio-Oss® scaffolds. Results obtained from qPCR and Luminex® indicate that WJ-MSCs possess the ability to differentiate into osteoblast-like cells and may induce osteoclastogenesis, angiogenesis, and mobilization of host MSCs. In animal studies, WJ-MSCs seeded on Bio-Oss® increased the scaffold integration with host bone and changed their morphology to osteoblast-like cells. Conclusions. The presented construct consisted of Bio-Oss®, the scaffold with high flexibility and plasticity, approved for clinical use with seeded immunologically privileged WJ-MSC which may be considered reconstructive therapy in bone defects. [ABSTRACT FROM AUTHOR]

Background. Abdominal wall weakness occurs when the strength of muscle decreases due to physiological reason or iatrogenic injury. However, the treatment of this disease is complicated. Aim. To study the therapeutic effect of acellular tissue matrix (ACTM), compared with the polypropylene mesh. Methods. An abdominal wall weakness model was established in rabbits through motor nerves cutting. The polypropylene mesh and ACTM were implanted in the left and right abdomen sides, respectively. Mechanical testing of abdominal wall muscle and histology and scanning electron microscopy (SEM) evaluation of abdominal tissue explants were performed. Results. In animal model establishment, the abdominal length of healthy and weakened abdominal wall was 17.0 ± 0.7 cm and 19.0 ± 1.2 cm, respectively (P = 0.022), and the weak abdominal wall group showed a significant decrease of 1.116 ± 0.221 MPa in tensile stress (P < 0.001) and 9.126 ± 2.073% in tensile strain (P < 0.001). In materials implantation experiment, compared with polypropylene group, ACTM group decreased 2.409 ± 0.806 MPa after 24 weeks (P < 0.001) and 2.319 ± 0.486 MPa after 48 weeks (P < 0.001) in tensile stress and increased 15.259% after 24 weeks (P < 0.001) and 15.845% after 48 weeks (P < 0.001) remarkably in tensile strain. Conclusion. The abdominal wall weakness model in rabbits was successfully established. ACTM is a promising biological material to be possibly further applied in clinical surgery in patients with abdominal wall weakness. [ABSTRACT FROM AUTHOR]

Bone marrow-derived stem/progenitor cells have been utilized for cardiac or vascular repair after ischemic injury, but they are subject to apoptosis and immune rejection in the ischemic site. Multiple scaffolds were used as delivery tools to transplant stem/progenitor cells; however, these scaffolds did not show intrinsically antiapoptotic or anti-inflammatory properties. Decellularized aortic scaffolds that facilitate cell delivery and tissue repair were prepared by removing cells of patient-derived aortic tissues. Scanning electron microscopy (SEM) showed cells attached well to the scaffold after culturing for 5 days. Live/dead staining showed most seeded cells survived at day 7 on a decellularized aortic scaffold. Ki67 staining demonstrated that decellularized aortic scaffold promoted proliferation of bone marrow-derived CD34+ progenitor cells. Apoptosis of CD34+ progenitor cells induced by H2O2 at high concentration was significantly alleviated in the presence of decellularized aortic scaffolds, demonstrating a protective effect against oxidative stress-induced apoptosis. Furthermore, decellularized aortic scaffolds significantly reduced the expression of proinflammatory cytokines (IL-8, GM-CSF, MIP-1β, GRO-α, Entoxin, and GRO) concurrently with an increase in anti-inflammatory cytokines (IL-2 and TGF-β) released from CD34+ progenitor cells when exposed to H2O2 at low concentration. Finally, neovascularization was observed by H&E and immunohistochemical staining 14 days after the decellularized aortic scaffolds were subcutaneously implanted in nude mice. This preclinical study demonstrates that the use of a decellularized aortic scaffold possessing antiapoptotic and anti-inflammatory properties may represent a promising strategy for cardiovascular repair after ischemic injury. [ABSTRACT FROM AUTHOR]

Poly-ε-caprolactone (PCL) is a promising synthetic material in bone tissue engineering (BTE). Particularly, the introduction of rapid prototyping (RP) represents the possibility of manufacturing PCL scaffolds with customized appearances and structures. Bio-Oss is a natural bone mineral matrix with significant osteogenic effects; however, it has limitations in being constructed and maintained into specific shapes and sites. In this study, we used RP and fabricated a hollow-structured cage-shaped PCL scaffold loaded with Bio-Oss to form a hybrid scaffold for BTE. Moreover, we adopted NaOH surface treatment to improve PCL hydrophilicity and enhance cell adhesion. The results showed that the NaOH-treated hybrid scaffold could enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells (hBMMSCs) both in vitro and in vivo. Altogether, we reveal a novel hybrid scaffold that not only possesses osteoinductive function to promote bone formation but can also be fabricated into specific forms. This scaffold design may have great application potential in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Highly open, porous polymer or poly(high internal phase emulsion) (polyHIPE) obtained from polymerized high internal phase emulsions (HIPE) have recently attracted much attention and increasing interest in tissue engineering applications because of their excellent properties. This research is aimed at preparing and developing a process for producing polyHIPE for use as a scaffold in tissue engineering applications. Poly(styrene/ethylene glycol dimethacrylate) (poly(S/EGDMA)) loaded with hydroxyapatite was used to prepare the polyHIPE. Further improvement on hydrophilicity and biological response to tissue fluids of the polyHIPE porous polymer was carried out using a nanolayer coating via the layer-by-layer polyelectrolyte multilayer (PEM) technique. Three types of chemicals were used for coating on the surface of the polyHIPE porous polymer such as poly(sodium 4-styrene sulfonate) (PSS), gelatin (GEL), and alginic acid (ALG). The change in surface properties of the modified poly(S/EGDMA)HIPE was characterized by UV-visible spectroscopy and contact angle measurement. Further assessments consisted of cytotoxicity testing, cell attachment, and proliferation of L929, fibroblast-like cells that were seeded on the surface of the polyHIPE porous polymer. A three-dimensional structure poly(S/EGDMA)HIPE porous polymer with high porosity was successfully prepared. Moreover, it was found that surface modification encouraged poly(S/EGDMA)HIPE with a hydrophilic nanolayer, as observed by the decrease in contact angle degree and cell adhesion of L929 fibroblast-like cells, indicating that the poly(S/EGDMA)HIPE porous polymer was effectively improved by using the layer-by-layer technique. It was revealed by MTT assay that the poly(S/EGDMA)HIPE porous polymer coated with a nanolayer of a polyelectrolyte multilayer led to an enhancement in the amount of cell adhesion and proliferation on the modified poly(S/EGDMA)HIPE porous polymer. Additionally, the most effective polyelectrolyte solution for improving cell adhesion of the poly(S/EGDMA)HIPE was PSS. [ABSTRACT FROM AUTHOR]