Additive manufacturing of bioactive glass biomaterials

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

A novel intervention technology for cerebral palsy: Brain stimulation

A common pediatric disorder with posture and motor dysfunction in neurological diseases is known as cerebral palsy (CP). Recently, a series of effective techniques have been developed for treatment of CP. These promising methods need high-tech equipment for brain stimulation and mainly classified into invasive and no-invasive approaches. This study aimed to introduce these techniques for treatment of patients who suffer from CP. The potential and performance of currently available brain stimulation techniques have been mentioned in detail. Moreover, the clinical application, safety, efficacy and challenges of these methods have been discussed. Here we review the recent advances in the CP treatment with an emphasis on brain stimulation techniques. © 2019, Iranian Child Neurology Society. All rights reserved

Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study.

Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay

3D-printed barium strontium titanate-based piezoelectric scaffolds for bone tissue engineering

In order to promote bone healing, new generations of biomaterials are under development. These biomaterials should demonstrate proper biological and mechanical properties preferably similar to the natural bone tissue. In this research, 3D-printed barium strontium titanate (BST)/β-tricalcium phosphate (β-TCP) composite scaffolds have been synthesized as an alternative strategy for bone regeneration to not only induce appropriate bioactive characteristics but also piezoelectric behavior. The physical, chemical and biological performance of the scaffolds have been examined in terms of mechanical, dielectric properties, apatite-forming ability, Alizarin Red Staining (ARS), Alkaline Phosphatase activity (ALP), and cytotoxicity. The samples composed of 60 BST and 40 β-TCP showed the highest compressive strength, bending module, elastic modulus and the Young's modulus. The dielectric constant increased with further addition of the BST phase in the constructs. Scanning Electron Microscope (SEM) and energy dispersive X-ray (EDX) analyses showed that 60 BST/40 β-TCP sample had the highest amount of bone-like apatite formation after 28 days in simulated body fluid (SBF). Moreover, the results of ARS proved that 60 BST/40 β-TCP composite could present higher quantities of mineral deposition. The ALP activity of osteosarcoma cells on 60 BST/40 β-TCP sample showed higher activities compare with the other composites. None of the samples demonstrated any sign of toxicity using MTT test. It can be suggested that BST/β-TCP composite scaffolds can be potentially used as the next generation of bone tissue engineering scaffold materials. © 2019 Elsevier Ltd and Techna Group S.r.l

Additively manufactured small-diameter vascular grafts with improved tissue healing using a novel SNAP impregnation method

The vascular network has a complex architecture such as branches, curvatures, and bifurcations which is even more complicated in view of individual patients' defect anatomy requiring custom-specifically designed vascular implants. In this work, 3D printing is used to overcome these challenges and a new shorter impregnation method was developed to incorporate S-nitroso-N-acetyl-d-penicillamine (SNAP) as a nitric oxide (NO) donor to printed grafts. The 3D-printed small-diameter vascular grafts (SDVGs) were impregnated with SNAP solution during SNAP synthesis (S1) or with SNAP dissolved in methanol (S2). The advantage of the newly developed S1 impregnation method is the elimination of the synthesis step by direct impregnation inside the S1 solution. Scanning electron microscopy imaging reveals the successful crystal formation in both methods. The results demonstrate that both S1- and S2-impregnated grafts, after covering with polycaprolactone topcoat, can release NO in a controlled manner and in the physiological range (0.5�4.0 � 10�10 mol cm�2 min�1) over a 15 days period. The created grafts with a NO-releasing surface have also shown bactericidal effect while the healing properties of the implant were improved by promoting migration and proliferation of endothelial cells (ECs). These results suggest that incorporation of 3D printing technology with the newly developed S1 impregnation of SNAP can optimize and shorten the manufacturing process of the next generation of patient-based antibacterial SDVGs with a higher attraction for ECs. © 2019 Wiley Periodicals, Inc

Nitric oxide-releasing vascular grafts: A therapeutic strategy to promote angiogenic activity and endothelium regeneration

Small-diameter vascular grafts (SDVGs) are associated with a high incidence of failure due to infection and obstruction. Although several vascular grafts are commercially available, specific anatomical differences of defect sites require patient-based design and fabrication. Design and fabrication of such custom-tailored grafts are possible with 3d-printing technology. The aim of this study is to develop 3d-printed SDVGs with a nitric oxide (NO)-releasing coating to improve the success rate of implantation. The SDVGs were printed from polylactic acid and coated with blending of 10 wt S-nitroso-N-acetyl-D-penicillamine into the polymeric substrate consisting of poly (ethylene glycol) and polycaprolactone. Our results show that NO is released in the physiological range (0.5�4 � 10�10 mol·cm�2·min�1) for 14 days and NO-releasing coating showed significant antibacterial potential against Gram-positive and Gram-negative strains. It was shown that both NO-releasing and control grafts are biocompatible in-vitro and in-vivo. Interestingly, the NO-releasing SDVGs dramatically enhanced ECs proliferation and significantly enhanced ECs migration in-vitro compared to control grafts. In addition, the NO-releasing SDVGs showed angiogenic potential in-vivo which can further prove the results of our in-vitro study. These findings are expected to facilitate tissue regeneration and integration of custom-made vascular implants with enhanced clinical success. Statement of significance: A series of 3d-printed small-diameter vascular grafts (SDVGs, <6 mm) with controlled release of nitric oxide (NO) were prepared to combine the advantages of 3D printing technology and NO-releasing systems. The resulting NO-releasing grafts were promisingly showing sustained NO release in the physiological range over a two weeks period. In addition to the evaluation of endothelial cell migration in-vitro, we implanted for the first time the NO-releasing vascular grafts in a chick chorioallantoic membrane (CAM) to investigate the effect of the prepared grafts on the angiogenesis in-vivo. The fabricated grafts also exhibited bactericidal properties which prevent the formation of a biofilm layer and can thereby enhance the chance of endothelialization on the surface. Taken together, the innovative combination of rapid and highly accurate 3d-printing technology as a patient-specific fabrication method with NO-releasing coating represents a promising approach to develop bactericidal SDVGs with improved endothelialization. © 2019 Acta Materialia Inc

Decellularization and preservation of human skin: A platform for tissue engineering and reconstructive surgery

A matrix derived from natural tissue functions as a highly biocompatible and versatile scaffold for tissue engineering applications. It can act as a supportive construct that provides a niche for colonization by host cells. In this work, we describe a cost-effective, reliable and reproducible protocol for decellularization and preservation of human skin as a potential soft tissue replacement. The decellularized human skin is achieved using purely chemical agents without any enzymatic steps. The suitability of the proposed method for the preservation of the extracellular matrix (ECM) structure and its main components and integrity were evaluated using histological and immunohistochemical analysis. Cryopreservation and final sterility were conducted using programmable freeze-drying and gamma irradiation. The architecture, basement membrane and 3D structure of ECM can be successfully preserved after decellularization. Our protocol was found to be appropriate to maintain key proteins such as collagen type I, III, IV and laminin in the structure of final scaffold. This protocol offers a novel platform for the preparation of a dermal substitute for potential clinical applications. Statement of Significance: Clinical application of naturally-based scaffolds for verity of health problems obliges development of a reproducible and effective technology that does not change structural and compositional material properties during scaffold preparation and preservation. Lack of an effective protocol for the production of biological products using decellularization method is still remaining. This effort is directing to solve this challenge in order to accomplish the off-the �shelf availability of decellularized dermal scaffold in market for clinical application. © 2019 Elsevier Inc

Thermo-responsive chitosan hydrogel for healing of full-thickness wounds infected with XDR bacteria isolated from burn patients: In vitro and in vivo animal model

Treatment of non-healing skin wounds infected with extensively drug-resistant (XDR) bacteria remains as a big challenge. To date, different biomaterials have been applied for treatment of post-wound infections, nevertheless their efficacy for treatment of the wounds infected with XDR isolates has not been determined yet. In this study, the potential of the thermo-responsive chitosan (TCTS) hydrogel for protection of full-thickness wounds XDR bacteria isolated from burn patients was evaluated both in vitro and in vivo in a rat model. Antibacterial activity of the TCTS hydrogel against standard strain and clinical isolates of Acinetobacter baumannii, cytobiocompatibility for Hu02 fibroblast cells, degradation rate and swelling ratio were determined in vitro. MTT assay and disk diffusion test indicated no detectable cytotoxicity and antibacterial activity in vitro, respectively. In vivo study showed significant acceleration of wound healing, re-epithelialization, wound closure, and decreased colony count in the TCTS hydrogel group compared with control. This study suggests TCTS hydrogel as an excellent wound dressing for management of the wounds infected with XDR bacteria, and now promises to proceed with clinical investigations. © 201

Osteogenic potential of stem cells-seeded bioactive nanocomposite scaffolds: A comparative study between human mesenchymal stem cells derived from bone, umbilical cord Wharton's jelly, and adipose tissue

Bone regeneration is considered as an unmet clinical need, the aim of this study is to investigate the osteogenic potential of three different mesenchymal stem cells (MSCs) derived from human bone marrow (BM-MSCs), umbilical cord Wharton's jelly (UC-MSCs), and adipose (AD-MSCs) seeded on a recently developed nanocomposite scaffold (bioactive glass/gelatin) implanted in rat animal models with critical size calvarial defects. In this study, after isolation, culture, and characterization, the MSCs were expanded and seeded on the scaffolds for in vitro and in vivo studies. The adhesion, proliferation, and viability of the cells on the scaffolds evaluated in vitro, showed that the scaffolds were biocompatible for further examinations. In order to evaluate the scaffolds in vivo, rat animal models with critical size calvarial defects were randomly categorized in four groups and treated with the scaffolds. The animals were sacrificed at the time points of 4 and 12 weeks of post-implantation, bone healing process were investigated. The histological and immunohistological observations showed (p < 0.01) higher osteogenesis capacity in the group treated with BM-MSCs/scaffolds compared to the other groups. However, the formation of new angiogenesis was evidently higher in the defects filled with UC-MSCs/scaffolds. This preliminary study provides promising data for further clinical trials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 61�72, 2018. © 2016 Wiley Periodicals, Inc