A ternary composite hydrogel based on sodium alginate, carboxymethyl cellulose and copper-doped 58S bioactive glass promotes cutaneous wound healing in vitro and in vivo.

Hydrogels offer a novel approach to wound repair. In this study, we synthesized a ternary composite using sodium alginate (SA), carboxymethyl cellulose (CMC) and copper-doped 58S bioactive glass (BG). According to our mechanical testing results, the composite made of 7 wt% CMC and 7 wt% BG (SA-7CMC-7BG) showed optimal properties. In addition, our in vitro studies revealed the biocompatibility and bioactivity of SA-7CMC-7BG, with a negative zeta potential of -31.7 mV. Scanning electron microscope (SEM) images showed 273-µm-diameter pores, cell adhesion, and anchoring. The SA-7CMC-7BG closed 90.4 % of the mechanical scratch after 2 days. An in vivo wound model using Wistar rats showed that SA-7CMC-7BG promoted wound healing, with 85.57 % of the wounds healed after 14 days. Treatment with the SA-7CMC-7BG hydrogel caused a 1.6-, 65-, and 1.87-fold increase in transforming growth factor beta (TGF-ß), Col I, and vascular endothelial growth factor (VEGF) expression, respectively that prevents fibrosis and promotes angiogenesis. Furthermore, interleukin 1ß (IL-1ß) expression was downregulated by 1.61-fold, indicating an anti-inflammatory effect of SA-7CMC-7BG. We also observed an increase in epidermal thickness, the number of fibroblast cells, and collagen deposition, which represent complementary pathology results confirming the effectiveness of the SA-7CMC-7BG hydrogel in cutaneous wound healing.

Smart alginate inks for tissue engineering applications.

Amazing achievements have been made in the field of tissue engineering during the past decades. However, we have not yet seen fully functional human heart, liver, brain, or kidney tissue emerge from the clinics. The promise of tissue engineering is thus still not fully unleashed. This is mainly related to the challenges associated with producing tissue constructs with similar complexity as native tissue. Bioprinting is an innovative technology that has been used to obliterate these obstacles. Nevertheless, natural organs are highly dynamic and can change shape over time; this is part of their functional repertoire inside the body. 3D-bioprinted tissue constructs should likewise adapt to their surrounding environment and not remain static. For this reason, the new trend in the field is 4D bioprinting - a new method that delivers printed constructs that can evolve their shape and function over time. A key lack of methodology for printing approaches is the scalability, easy-to-print, and intelligent inks. Alginate plays a vital role in driving innovative progress in 3D and 4D bioprinting due to its exceptional properties, scalability, and versatility. Alginate's ability to support 3D and 4D printing methods positions it as a key material for fueling advancements in bioprinting across various applications, from tissue engineering to regenerative medicine and beyond. Here, we review the current progress in designing scalable alginate (Alg) bioinks for 3D and 4D bioprinting in a "dry"/air state. Our focus is primarily on tissue engineering, however, these next-generation materials could be used in the emerging fields of soft robotics, bioelectronics, and cyborganics.

Wound healing performance of electrospun PVA/70S30C bioactive glass/Ag nanoparticles mats decorated with curcumin: In vitro and in vivo investigations.

Biocompatible fibrous scaffold containing polyvinyl alcohol (PVA), 70S30C bioactive glass (BG), silver (Ag) nanoparticles and curcumin (Cur) was fabricated through electrospinning method. Scanning electron microscope (SEM) and Field emission scanning electron microscopy (FESEM) were employed to investigate the morphological characteristics of the scaffolds. In addition, biodegradability, hydrophilicity, and contact angle were studied as criteria for evaluating physical properties of the scaffolds. Tensile strength was reported to be 0.971 ± 0.093 MPa. Also, the viability of fibroblasts after 7 days of cell culture was 93.58 ± 1.36 %. The antibacterial activity against Escherichia coli and Staphylococcus aureus bacteria was illustrated using inhibition zones of 13.12 ± 0.69 and 14.21 ± 1.37 mm, respectively. Histological results revealed that tissue regeneration after 14 days of surgery was much higher for the dressing group compared to the blank group. According to the obtained results, the authors introduce the PVA-BG-Ag-Cur scaffold as a promising candidate for skin tissue engineering applications.

Multi-leveled Nanosilicate Implants Can Facilitate Near-Perfect Bone Healing.

Several studies have shown that nanosilicate-reinforced scaffolds are suitable for bone regeneration. However, hydrogels are inherently too soft for load-bearing bone defects of critical sizes, and hard scaffolds typically do not provide a suitable three-dimensional (3D) microenvironment for cells to thrive, grow, and differentiate naturally. In this study, we bypass these long-standing challenges by fabricating a cell-free multi-level implant consisting of a porous and hard bone-like framework capable of providing load-bearing support and a softer native-like phase that has been reinforced with nanosilicates. The system was tested with rat bone marrow mesenchymal stem cells in vitro and as a cell-free system in a critical-sized rat bone defect. Overall, our combinatorial and multi-level implant design displayed remarkable osteoconductivity in vitro without differentiation factors, expressing significant levels of osteogenic markers compared to unmodified groups. Moreover, after 8 weeks of implantation, histological and immunohistochemical assays indicated that the cell-free scaffolds enhanced bone repair up to approximately 84% following a near-complete defect healing. Overall, our results suggest that the proposed nanosilicate bioceramic implant could herald a new age in the field of orthopedics.

A Cohesive Shear-Thinning Biomaterial for Catheter-Based Minimally Invasive Therapeutics.

Shear-thinning hydrogels are suitable biomaterials for catheter-based minimally invasive therapies; however, the tradeoff between injectability and mechanical integrity has limited their applications, particularly at high external shear stress such as that during endovascular procedures. Extensive molecular crosslinking often results in stiff, hard-to-inject hydrogels that may block catheters, whereas weak crosslinking renders hydrogels mechanically weak and susceptible to shear-induced fragmentation. Thus, controlling molecular interactions is necessary to improve the cohesion of catheter-deployable hydrogels. To address this material design challenge, we have developed an easily injectable, nonhemolytic, and noncytotoxic shear-thinning hydrogel with significantly enhanced cohesion via controlling noncovalent interactions. We show that enhancing the electrostatic interactions between weakly bound biopolymers (gelatin) and nanoparticles (silicate nanoplatelets) using a highly charged polycation at an optimum concentration increases cohesion without compromising injectability, whereas introducing excessive charge to the system leads to phase separation and loss of function. The cohesive biomaterial is successfully injected with a neuroendovascular catheter and retained without fragmentation in patient-derived three-dimensionally printed cerebral aneurysm models under a physiologically relevant pulsatile fluid flow, which would otherwise be impossible using the noncohesive hydrogel counterpart. This work sheds light on how charge-driven molecular and colloidal interactions in shear-thinning physical hydrogels improve cohesion, enabling complex minimally invasive procedures under flow, which may open new opportunities for developing the next generation of injectable biomaterials.

The anticancer properties of metal-organic frameworks and their heterogeneous nanocomposites.

Herein, silver-based metal-organic framework (AgMOF) and its graphene oxide (GO)-decorated nanocomposite (GO-AgMOF) are proposed for use in emerging biomedical applications. The nanocomposites are characterized, and hence, in vitro apoptotic and antibacterial features of AgMOF and GO-AgMOF nanomaterials were investigated. An MTT cytocompatibility assay indicates that these nanomaterials have dose-dependent toxicity in contact with SW480, colon adenocarcinoma cells. In addition, the cell death mechanism was explored by analyzing flow cytometry and caspase activity. Furthermore, the expressions of pro-apoptotic and anti-apoptotic genes were investigated using quantitative polymerase chain reaction (qPCR). Comparing the control group with the groups treated by the nanomaterials indicates up-regulation of the BAX/BCl2 ratio. We also measured the minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) of these nanomaterials acting on S. mutans and S. aureus, which indicates excellent antibacterial properties. Showing inhibition effect on the viability of cancerous cells through apoptosis and antibacterial effects simultaneously, AgMOF and GO-AgMOF can be regarded as potential therapeutics for cancer.

Aloe vera incorporated starch-64S bioactive glass-quail egg shell scaffold for promotion of bone regeneration.

Simultaneous promotion of osteoconductive and osteoinductive characteristics through combining bioactive glasses with natural polymers is still a challenge in bone tissue engineering. Starch, 64S bioactive glass (BG), aloe vera (AV) and quail eggshell powder (QE) were utilized to achieve biodegradable, bioactive, biocompatible and mechanically potent multifunctional scaffolds, using freeze-drying mechanism. Cell viability for starch-BG-AV-QE scaffolds at 3 and 7 day intervals was reported to be over 95 %. Acridine orange staining was employed to study live/dead cells cultured on the scaffolds. The high sufficiency of starch-BG-AV-QE scaffolds in osteogenic differentiation and extracellular matrix mineralization was confirmed through alkaline phosphatase activity and alizarin red staining assessments after 7 and 14 days of cell culture. High compressive strength, managed biodegradability and expression of osteocalcin and osteopontin as late markers of osteogenic differentiation were also reached in the range of 30-75 % for starch-BG-AV-QE scaffolds. Hence, starch-BG-AV-QE scaffolds with ideal physico-mechanical and biological characteristics can be considered as promising candidates for promotion of bone regeneration.

Assessing the aneurysm occlusion efficacy of a shear-thinning biomaterial in a 3D-printed model.

Metallic coil embolization is a common method for the endovascular treatment of visceral artery aneurysms (VAA) and visceral artery pseudoaneurysms (VAPA); however, this treatment is suboptimal due to the high cost of coils, incomplete volume occlusion, poor reendothelialization, aneurysm puncture, and coil migration. Several alternative treatment strategies are available, including stent flow diverters, glue embolics, gelfoam slurries, and vascular mesh plugs-each of which have their own disadvantages. Here, we investigated the in vitro capability of a shear-thinning biomaterial (STB), a nanocomposite hydrogel composed of gelatin and silicate nanoplatelets, for the minimally-invasive occlusion of simple necked aneurysm models. We demonstrated the injectability of STB through various clinical catheters, engineered an in vitro testing apparatus to independently manipulate aneurysm neck diameter, fluid flow rate, and flow waveform, and tested the stability of STB within the models under various conditions. Our experiments show that STB is able to withstand at least 1.89 Pa of wall shear stress, as estimated by computational fluid dynamics. STB is also able to withstand up to 10 mL s-1 pulsatile flow with a waveform mimicking blood flow in the human femoral artery and tolerate greater pressure changes than those in the human aorta. We ultimately found that our in vitro system was limited by supraphysiologic pressure changes caused by aneurysm models with low compliance.

Multifunctional polyethylene imine hybrids decorated by silica bioactive glass with enhanced mechanical properties, antibacterial, and osteogenesis for bone repair.

Inorganic/organic hybrids and bioactive glasses demonstrate promising potential as bone substitute biomaterials. A sol-gel hybrid consisting of silica bioactive glass and biodegradable polymer can combine the high bioactivity of a glass with the toughness of a polymer. In this study, multifunctional hybrids with a combination of organic-inorganic hybrid structure class II consisting of polyethyleneimine (PEI) generation 4 (G4) and bioactive glass with enhanced mechanical properties, mineralization, antibacterial, and osteogenesis activities were synthesized by the sol-gel method. Glycidoxypropyl) trimethoxysilane (GPTMS) with different concentrations was used as a covalent bonding agent between PEI polymer and bioactive glass. The effect of GPTMS content was assessed in the presence and absence of calcium in the hybrid structures in terms of morphology, wettability, mechanical properties, antibacterial activity, cell viability, and in vitro osteogenic differentiation properties. By increasing the amount of GPTMS, the compressive strength increased from 1.95 MPa to 2.34 MPa, which was comparable to human trabecular bone. All the hybrids presented antibacterial activity against Staphylococcus aureus, forming an inhibition zone of 13-16 mm. An increase in cell viability of 82.22% in PSCaG90 was obtained after 1 day of MG-63 cell culture. Alkaline phosphatase expression and mineralization of MG-63 cells increased in the PSCaG90 hybrid in the absence of an osteogenic medium compared to PSG60 and PSG90. The PSCaG90 hybrid indicated considerable in vitro osteogenic capacity in the absence of a differentiation medium, expressing high levels of bone-specific proteins including collagen I (COL1A1), Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN), compared to calcium-free hybrids. Overall, our results suggest that the presence of calcium in the PSCaG90 leads to a significant increase in osteogenic differentiation of MG-63 cells even in the absence of differentiation medium, which suggests these hybrid structures with multifunctional properties as promising candidates for bone repair.

Use of electroconductive biomaterials for engineering tissues by 3D printing and 3D bioprinting.

Existing methods of engineering alternatives to restore or replace damaged or lost tissues are not satisfactory due to the lack of suitable constructs that can fit precisely, function properly and integrate into host tissues. Recently, three-dimensional (3D) bioprinting approaches have been developed to enable the fabrication of pre-programmed synthetic tissue constructs that have precise geometries and controlled cellular composition and spatial distribution. New bioinks with electroconductive properties have the potential to influence cellular fates and function for directed healing of different tissue types including bone, heart and nervous tissue with the possibility of improved outcomes. In the present paper, we review the use of electroconductive biomaterials for the engineering of tissues via 3D printing and 3D bioprinting. Despite significant advances, there remain challenges to effective tissue replacement and we address these challenges and describe new approaches to advanced tissue engineering.

On the role of alginate coating on the mechanical and biological properties of 58S bioactive glass scaffolds.

In this study, novel 3D porous alginate-coated 58S bioactive glass scaffolds were fabricated through a foam replication method using a combination of amorphous 58S bioactive glass structure and sodium alginate. The formation of the alginate coating on the surface of the struts of BG scaffolds was confirmed. The effect of alginate coating on the microstructure, mechanical properties, biodegradability, biomineralization, adhesion, viability, and differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) on the 58S BG scaffolds were evaluated. A 45.2% increase in hMSC's viability and a 3.4-fold increase in ALP activity of the 1AlBG scaffold in the absence of an osteogenic differentiation media compared to an uncoated BG scaffold were observed. Notably, gene expression analysis exhibited that the 1AlBG scaffold resulted in accelerated osteogenic differentiation of hMSCs, as expression of COL-1, RUNX2, and OCN increased after 14 days. Results revealed a significant increase of antibacterial inhibition in the 1AlBG scaffold in comparison to the BG scaffold. Based on the microstructural, mechanical, and biological investigations, the 1AlBG scaffold exhibited enhanced mechanical and biological properties, making it a promising candidate for bone regeneration. Overall, our findings have highlighted the potential of alginate-coated BG scaffolds to stimulate bone regeneration through stem cell osteoinduction.

A highly bioactive poly (amido amine)/70S30C bioactive glass hybrid with photoluminescent and antimicrobial properties for bone regeneration.

The field of tissue engineering constantly calls for novel biomaterials that possess intrinsically multifunctional properties such as bioactivity, bioimaging ability and antibacterial properties. In this paper, poly (amido amine) generation 5/bioactive glass inorganic-organic hybrids have been developed through direct hybridization by 3-glycidoxypropyltrimethoxysilane (GPTMS) as coupling agent. Results indicated that the degree of covalent coupling by GPTMS and the weight percent of inorganic and organic constituents highly influence hybrids properties. It was found that nanoscale integration of inorganic and organic chains by GPTMS significantly endows hybrids with high thermal stability. Furthermore, hybrids exhibited photoluminescent ability (emission 400-600nm and 700nm) without incorporating of any organic dyes or quantum dots. In addition, hydrophilicity of our hybrids indicated good cell/material interaction. The biological apatite was formed on the surface of calcium containing hybrids when soaked in simulated body fluid (SBF) for 1week. Hybrids also showed linear biodegradation behavior in SBF that could be controlled by the degree of covalent crosslinking which was indicative of their stable biodegradation ability. High inherent antibacterial properties against Staphylococcus aureus was also observed from poly (amido amine)/silica hybrids. No adverse cytotoxicity for human gingival fibroblast cell lines (HGF) was detected after 4days. It is envisaged that our novel multifunctional hybrid system will confer intriguing potential in advancing the field of tissue engineering.