Wave-attenuation characteristics of combined-vegetation wave break forests for big rivers with large flood water level changes.

For large rivers with a compound cross section, the downstream channel has a very wide water surface during the flood season. A wide water surface, high water level, and larger wind speed will cause higher waves, increasing the threat of flooding to the dike. The design of a combined-vegetation wave break forest was put forward to achieve better wave attenuation effect. The main idea of this concept is to plant different types of vegetation at different locations in front of the dike. Three single-vegetation and four combined-vegetation forest schemes were tested under seven different water depth conditions. Both physical experiments and wave numerical simulations were carried out for each scheme to study the wave attenuation effect. The results showed that the wave attenuation effect of the single-vegetation wave break forest was significantly different under different water depth conditions, and the overall effect of the combined-vegetation of wave forest was better. Combined-vegetation wave break forests combine the advantages of different types of vegetation in different water levels, which makes it more economical and reasonable to plant by rivers with large water level variation. The proposed design ideas and methods could provide theoretical support for ecological revetment engineering of large rivers and insights for practical applications.

Healthcare Data Gateways: Found Healthcare Intelligence on Blockchain with Novel Privacy Risk Control.

Healthcare data are a valuable source of healthcare intelligence. Sharing of healthcare data is one essential step to make healthcare system smarter and improve the quality of healthcare service. Healthcare data, one personal asset of patient, should be owned and controlled by patient, instead of being scattered in different healthcare systems, which prevents data sharing and puts patient privacy at risks. Blockchain is demonstrated in the financial field that trusted, auditable computing is possible using a decentralized network of peers accompanied by a public ledger. In this paper, we proposed an App (called Healthcare Data Gateway (HGD)) architecture based on blockchain to enable patient to own, control and share their own data easily and securely without violating privacy, which provides a new potential way to improve the intelligence of healthcare systems while keeping patient data private. Our proposed purpose-centric access model ensures patient own and control their healthcare data; simple unified Indicator-Centric Schema (ICS) makes it possible to organize all kinds of personal healthcare data practically and easily. We also point out that MPC (Secure Multi-Party Computing) is one promising solution to enable untrusted third-party to conduct computation over patient data without violating privacy.

Context-Awareness Based Personalized Recommendation of Anti-Hypertension Drugs.

The World Health Organization estimates that almost one-third of the world's adult population are suffering from hypertension which has gradually become a "silent killer". Due to the varieties of anti-hypertensive drugs, patients are interested in how these drugs can be selected to match their respective conditions. This study provides a personalized recommendation service system of anti-hypertensive drugs based on context-awareness and designs a context ontology framework of the service. In addition, this paper introduces a Semantic Web Rule Language (SWRL)-based rule to provide high-level context reasoning and information recommendation and to overcome the limitation of ontology reasoning. To make the information recommendation of the drugs more personalized, this study also devises three categories of information recommendation rules that match different priority levels and uses a ranking algorithm to optimize the recommendation. The experiment conducted shows that combining the anti-hypertensive drugs personalized recommendation service context ontology (HyRCO) with the optimized rule reasoning can achieve a higher-quality personalized drug recommendation service. Accordingly this exploratory study of the personalized recommendation service for hypertensive drugs and its method can be easily adopted for other diseases.

Undifferentially Expressed CXXC5 as a Transcriptionally Regulatory Biomarker of Breast Cancer.

This work hypothesizes that some genes undergo radically changed transcription regulations (TRs) in breast cancer (BC), but don't show differential expressions for unknown reasons. The TR of a gene is quantitatively formulated by a regression model between the expression of this gene and multiple transcription factors (TFs). The difference between the predicted and real expression levels of a gene in a query sample is defined as the mqTrans value of this gene, which quantitatively reflects its regulatory changes. This work systematically screens the undifferentially expressed genes with differentially expressed mqTrans values in 1036 samples across five datasets and three ethnic groups. This study calls the 25 genes satisfying the above hypothesis in at least four datasets as dark biomarkers, and the strong dark biomarker gene CXXC5 (CXXC Finger Protein 5) is even supported by all the five independent BC datasets. Although CXXC5 does not show differential expressions in BC, its transcription regulations show quantitative associations with BCs in diversified cohorts. The overlapping long noncoding RNAs (lncRNAs) may have contributed their transcripts to the expression miscalculations of dark biomarkers. The mqTrans analysis serves as a complementary view of the transcriptome-based detections of biomarkers that are ignored by many existing studies.

Lithium-Induced Optimization Mechanism for an Ultrathin-Strut Biodegradable Zn-Based Vascular Scaffold.

To reduce incidences of in-stent restenosis and thrombosis, the use of a thinner-strut stent has been clinically proven to be effective. Therefore, the contemporary trend is toward the use of ultrathin-strut (≤70 µm) designs for durable stents. However, stents made from biodegradable platforms have failed to achieve intergenerational breakthroughs due to their excessively thick struts. Here, microalloying is used to create an ultrathin-strut (65 µm) zinc (Zn) scaffold with modified biodegradation behavior and improved biofunction, by adding lithium (Li). The scaffold backbone consists of an ultrafine-grained Zn matrix (average grain diameter 2.28 µm) with uniformly distributed nanoscale Li-containing phases. Grain refinement and precipitation strengthening enable it to achieve twice the radial strength with only 40% of the strut thickness of the pure Zn scaffold. Adding Li alters the thermodynamic formation pathways of products during scaffold biodegradation, creating an alkaline microenvironment. Li2 CO3  may actively stabilize this microenvironment due to its higher solubility and better buffering capability than Zn products. The co-release of ionic zinc and lithium enhances the beneficial differential effects on activities of endothelial cells and smooth muscle cells, resulting in good endothelialization and limited intimal hyperplasia in porcine coronary arteries. The findings here may break the predicament of the next-generation biodegradable scaffolds.

Noncoplanar intensity-modulated radiation therapy for young female patients with mediastinal lymphoma.

The purpose of this study is to apply noncoplanar intensity-modulated radiation therapy (Nonco_IMRT) to young female patients with mediastinal lymphoma. Nonco_IMRT was evaluated through a planning comparison study with coplanar IMRT (Co_IMRT) and conventional anteroposterior and posteroanterior fields (AP-PA) plans. Co_IMRT was performed with five equally spaced beams starting from a gantry angle of 216°. Nonco_IMRT used two noncoplanar beams in the sagittal plane to replace the Co_IMRT beams that directly irradiated the breasts. Nineteen young female patients were enrolled in the retrospective study. Dose coverage of the planning target volume (PTV) and the dose delivered to organs at risk (OARs) were analyzed. For all patients, PTV coverage and heart V30 were similar between the two IMRT techniques (p > 0.05). Compared to Co_IMRT, the mean dose delivered and regions receiving a low radiation dose were significantly reduced for bilateral breasts and lungs in Nonco_IMRT (p < 0.05). Breast V5 and lung V5 were relatively reduced by 21% and 12%, respectively. Compared with the conventional AP-PA plan, Nonco_IMRT had better PTV coverage and OARs sparing, except for being larger in V5 to breast and lung. In IMRT for young female patients with mediastinal lymphoma, using of Nonco_IMRT significantly reduces the radiation dose to the breasts and lungs compared with Co_IMRT, and consequently reduces the risk of breast second cancer and pulmonary toxicity. Besides young female patients, Nonco_IMRT can also benefit other mediastinal lymphoma patients.

A functional PVA aerogel-based membrane obtaining sutureability through modified electrospinning technology and achieving promising anti-adhesion effect after cardiac surgery.

Pericardial barrier destruction, inflammatory cell infiltration, and fibrous tissue hyperplasia, trigger adhesions after cardiac surgery. There are few anti-adhesion materials that are both functional and sutureable for pericardial reconstruction. Besides, a few studies have reported on the mechanism of preventing pericardial adhesion. Herein, a functional barrier membrane with sutureability was developed via a modified electrospinning method. It was composed of poly(l-lactide-co-caprolactone) (PLCL) nanofibers, poly(vinyl alcohol) (PVA) aerogel, and melatonin, named PPMT. The PPMT had a special microstructure manifested as a staggered arrangement of nanofibers on the surface and a layered macroporous aerogel structure in a cross-section. Besides providing the porosity and hydrophilicity obtained from PVA, the structure also had suitable mechanical properties for stitching due to the addition of PLCL nanofibers. Furthermore, it inhibited the proliferation of fibroblasts by suppressing the activation of Fas and P53, and achieved anti-inflammatory effects by affecting the activity of inflammatory cells and reducing the release of pro-inflammatory factors, such as interleukin 8 (IL-8) and tumor necrosis factor α (TNF-α). Finally, in vivo transplantation showed that it up-regulated the expression of matrix metalloproteinase-1 (MMP1) and tissue inhibitor of metalloproteinase-1 (TIMP1), and down-regulated the expression of Vinculin and transforming growth factor ß (TGF-ß) in the myocardium, thereby reducing the formation of adhesions. Collectively, these results demonstrate a great potential of PPMT membrane for practical application to anti-adhesion.

The solvent effect modulates the formation of homogeneous polyphenol composite hydrogels with improved transparency and mechanical strength for antibacterial delayed sternal closure films.

The usage of delayed sternal closure films after thoracotomy surgery helps doctors deal with emergency conveniently. There is a growing demand to develop suturable, antibacterial and transparent films for delayed sternal closure. Although polyphenol incorporated hydrogels provide good suture ability, they lose transparency because of the heterogeneous distribution of polyphenols during the post-immersion process. Here, a solvent exchange method is proposed to fabricate homogeneous polyphenol composite hydrogels in a bottom-up manner, which utilizes the distinct solvent effect of DMSO and H2O to modulate the association and disassociation between polyphenols and the polymer backbones on demand. DMSO first provides a protective environment to turn off the intermolecular interactions and allows tannic acid (TA) to be dispersed into the polymer network PEG-lysozyme (PEG-LZM) homogeneously. The following water rehydration turns on the intermolecular interactions between titanic acid and PEG-lysozymes, and results in a homogeneous titanic acid toughened composite hydrogel (PEG-LZM-TA (DH)), which has an improved transparency and mechanical properties than those of the materials prepared by the post-immersion method. In addition, the TA integration provides antibacterial function to the hydrogels. We establish a rabbit delayed sternal closure model to demonstrate that PEG-LZM-TA (DH) films can be sutured to temporarily close the thoracic cavity of rabbits, provide a transparent window to inspect the wound at any time, and control the bacterial contamination efficiently. We further explore the solvent exchange method to other polyphenols and polymeric hydrogel composites. The results suggest that the solvent exchange method provides generic opportunities to fabricate homogeneous polyphenol strengthened hydrogel systems with high performance.

Electro-assembly of a dynamically adaptive molten fibril state for collagen.

Collagen is a biological building block that is hierarchically assembled into diverse morphological structures that, in some cases, is dynamically adaptive in response to external cues and in other cases forms static terminal structures. Technically, there is limited capabilities to guide the emergence of collagen's hierarchical organization to recapitulate the richness of biological structure and function. Here, we report an electro-assembly pathway to create a dynamically adaptive intermediate molten fibril state for collagen. Structurally, this intermediate state is composed of partially aligned and reversibly associating fibrils with limited hierarchical structure. These molten fibrils can be reversibly reconfigured to offer dynamic properties such as stimuli-stiffening, stimuli-contracting, self-healing, and self-shaping. Also, molten fibrils can be guided to further assemble to recapitulate the characteristic hierarchical structural features of native collagen (e.g., aligned fibers with D-banding). We envision that the electro-assembly of collagen fibrils will provide previously unidentified opportunities for tailored collagen-based biomedical materials.

Vascular transplantation with dual-biofunctional ePTFE vascular grafts in a porcine model.

Cardiovascular disease (CVD) poses serious health concerns worldwide. The lack of transplantable vascular grafts is an unmet clinical need in the surgical treatment of CVD. Although expanded polytetrafluoroethylene (ePTFE) vascular grafts have been used in clinical practice, a low long-term patency rate in small-diameter transplantation application is still the biggest challenge. Thus, surface modification of ePTFE is sought after. In this study, polydopamine (PDA) was used to improve the hydrophilia and provide immobilization sites in ePTFE. Bivalirudin (BVLD), a direct thrombin inhibitor, was used to enhance the anti-thrombotic activity of ePTFE. The peptides derived from extracellular matrix proteins were used to elevate the bioactivity of ePTFE. The morphology, chemical composition, peptide modified strength, wettability, and hemocompatibility of modified ePTFE vascular grafts were investigated. Then, an endothelial cell proliferation assay was used to evaluate the best co-modification strategy of the ePTFE vascular graft in vitro. Since a large animal could relatively better mimic human physiology, we chose a porcine carotid artery replacement model in the current study. The results showed that the BVLD/REDV co-modified ePTFE vascular grafts had a satisfactory patency rate (66.7%) and a higher endothelial cell coverage ratio (70%) at 12 weeks after implantation. This may offer an opportunity to produce a multi-biofunctional ePTFE vascular graft, thereby yielding a potent product to meet the clinical needs.

Enlisting a Traditional Chinese Medicine to tune the gelation kinetics of a bioactive tissue adhesive for fast hemostasis or minimally invasive therapy.

Gelation kinetics is important in tailoring chemically crosslinked hydrogel-based injectable adhesives for different applications. However, the regulation of gelation rate is usually limited to varying the gel precursor and/or crosslinker concentration, which cannot reach a fine level and inevitably alters the physical properties of hydrogels. Amidation reactions are widely used to synthesize hydrogel adhesives. In this work, we propose a traditional Chinese medicine (Borax)-input strategy to tune the gelation rate of amidation reaction triggered systems. Borax provides an initial basic buffer environment to promote the deprotonation process of amino groups and accelerate this reaction. By using a tissue adhesive model PEG-lysozyme (PEG-LZM), the gelation time can be modulated from seconds to minutes with varying Borax concentrations, while the physical properties remain constant. Moreover, the antibacterial ability can be improved due to the bioactivity of Borax. The hydrogel precursors can be regulated to solidify instantly to close the bleeding wound at emergency. Meanwhile, they can also be customized to match the flowing time in the catheter, thereby facilitating minimally invasive tissue sealing. Because this method is easily operated, we envision Borax adjusted amidation-type hydrogel has a promising prospect in clinical application.

Nitric oxide-releasing poly(ε-caprolactone)/S-nitrosylated keratin biocomposite scaffolds for potential small-diameter vascular grafts.

Rapid endothelialization and regulation of smooth muscle cell proliferation are crucial for small-diameter vascular grafts to address poor compliance, thromboembolism, and intimal hyperplasia, and achieve revascularization. As a gaseous signaling molecule, nitric oxide (NO) regulates cardiovascular homeostasis, inhibits blood clotting and intimal hyperplasia, and promotes the growth of endothelial cells. Due to the instability and burst release of small molecular NO donors, a novel biomacromolecular donor has generated increasing interest. In the study, a low toxic NO donor of S-nitrosated keratin (KSNO) was first synthesized and then coelectrospun with poly(ε-caprolactone) to afford NO-releasing small-diameter vascular graft. PCL/KSNO graft was capable to generate NO under the catalysis of ascorbic acid (Asc), so the graft selectively elevated adhesion and growth of human umbilical vein endothelial cells (HUVECs), while inhibited the proliferation of human aortic smooth muscle cells (HASMCs) in the presence of Asc. In addition, the graft displayed significant antibacterial properties and good blood compatibility. Animal experiments showed that the biocomposite graft could inhibit thrombus formation and preserve normal blood flow via single rabbit carotid artery replacement for 1 month. More importantly, a complete endothelium was observed on the lumen surface. Taken together, PCL/KSNO small-diameter vascular graft has potential applications in vascular tissue engineering with rapid endothelialization and vascular remolding.

Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery.

Nitric oxide (NO) is a short-lived signaling molecule that plays a pivotal role in cardiovascular system. Organic nitrates represent a class of NO-donating drugs for treating coronary artery diseases, acting through the vasodilation of systemic vasculature that often leads to adverse effects. Herein, we design a nitrate-functionalized patch, wherein the nitrate pharmacological functional groups are covalently bound to biodegradable polymers, thus transforming small-molecule drugs into therapeutic biomaterials. When implanted onto the myocardium, the patch releases NO locally through a stepwise biotransformation, and NO generation is remarkably enhanced in infarcted myocardium because of the ischemic microenvironment, which gives rise to mitochondrial-targeted cardioprotection as well as enhanced cardiac repair. The therapeutic efficacy is further confirmed in a clinically relevant porcine model of myocardial infarction. All these results support the translational potential of this functional patch for treating ischemic heart disease by therapeutic mechanisms different from conventional organic nitrate drugs.

A reduced polydopamine nanoparticle-coupled sprayable PEG hydrogel adhesive with anti-infection activity for rapid wound sealing.

There is a growing demand to develop sprayable hydrogel adhesives with rapid-forming and antibacterial abilities to instantly seal open wounds and combat pathogen infection. Herein, we propose to design a polydopamine nanoparticle (PDA NP) coupled PEG hydrogel that can quickly solidify via an amidation reaction after spraying as well as tightly binding PDA NPs to deliver reactive oxygen species (ROS) and induce a photothermal effect for bactericidal activity, and provide a hydrophilic surface for antifouling activity. The molecular structure of the 4-arm-PEG-NHS precursor was regulated to increase its reactivity with 4-arm-PEG-NH2, which thus shortened the gelation time of the PEG adhesive to 1 s to allow a fast solidification after being sprayed. The PEG-NHS precursor also provided covalent binding with tissue and PDA NPs. The reduced PDA NPs have redox activity to convey electrons to oxygen to generate ROS (H2O2), thus endowing the hydrogel with ROS dependent antibacterial ability. Moreover, NIR irradiation can accelerate the ROS release because of the photothermal effect of PDA NPs. In vitro tests demonstrated that H2O2 and the NIR-photothermal effect synergistically induced a fast bacterial killing, and an in vivo anti-infection test also proved the effectiveness of PEG-PDA. The sprayable PEG-PDA hydrogel adhesive, with rapid-forming performance and a dual bactericidal mechanism, may be promising for sealing large-scale and acute wound sites or invisible bleeding sites, and protect them from pathogen infection.

Coupling PEG-LZM polymer networks with polyphenols yields suturable biohydrogels for tissue patching.

Poor mechanical performances severely limit the application of hydrogels in vivo; for example, it is difficult to perform a very common suturing operation on hydrogels during surgery. There is a growing demand to improve the mechanical properties of hydrogels for broadening their clinical applications. Natural polyphenols can match the potential toughening sites in our previously reported PEG-lysozyme (LZM) hydrogel because polyphenols have unique structural units including a hydroxyl group and an aromatic ring that can interact with PEG via hydrogen bonding and form hydrophobic interactions with LZM. By utilizing polyphenols as noncovalent crosslinkers, the resultant PEG-LZM-polyphenol hydrogel presents super toughness and high elasticity in comparison to pristine PEG-LZM with no obvious changes in the initial shape, and it can even withstand the high pressure from sutures. At the same time, the mechanical properties could be widely adjusted by varying the polyphenol concentration. Interestingly, the PEG-LZM-polyphenol hydrogel has a higher water content than other polyphenol-toughened hydrogels, which may better meet the clinical needs for hydrogel materials. Besides, the introduction of polyphenols endows the hydrogel with improved antibacterial and anti-inflammatory abilities. Finally, the PEG-LZM-polyphenol (tannic acid) hydrogel was demonstrated to successfully patch a rabbit myocardial defect by suturing for 4 weeks and improve the wound healing and heart function recovery compared to autologous muscle patches.

A biodegradable multifunctional nanofibrous membrane for periodontal tissue regeneration.

Biomaterial-based membranes represent a promising therapeutic option for periodontal diseases. Although conventional periodontal membranes function greatly in preventing the ingrowth of both fibroblasts and epithelial cells as well as connective tissues, they are not capable of promoting periodontal tissue regeneration. Here, we report a multifunctional periodontal membrane prepared by electrospinning biodegradable polymers with magnesium oxide nanoparticles (nMgO). nMgO is a light metal-based nanoparticle with high antibacterial capacity and can be fully resorbed in the body. Our results showed that incorporating nMgO into poly(L-lactic acid) (PLA)/gelatin significantly improved the overall properties of membranes, including elevated tensile strength to maintain structural stability and adjusted degradation rate to fit the time window of periodontal regeneration. Acidic degradation products of PLA were neutralized by alkaline ions from nMgO hydrolysis, ameliorating pH microenvironment beneficial for cell proliferation. In vitro studies demonstrated considerable antibacterial and osteogenic properties of nMgO-incorporated membranes that are highly valuable for periodontal regeneration. Further investigations in a rat periodontal defect model revealed that nMgO-incorporated membranes effectively guided periodontal tissue regeneration. Taken together, our data indicate that nMgO-incorporated membranes might be a promising therapeutic option for periodontal regeneration. STATEMENT OF SIGNIFICANCE: Traditional clinical treatments of periodontal diseases largely focus on the management of the pathologic processes, which cannot effectively regenerate the lost periodontal tissue. GTR, a classic method for periodontal regeneration, has shown promise in clinical practice. However, the current membranes might not fully fulfill the criteria of ideal membranes. Here, we report bioabsorbable nMgO-incorporated nanofibrous membranes prepared by electrospinning to provide an alternative for the clinical practice of GTR. The membranes not only function greatly as physical barriers but also exhibit high antibacterial and osteoinductive properties. We therefore believe that this study will inspire more practice work on the development of effective GTR membranes for periodontal regeneration.

A PEG-Lysozyme hydrogel harvests multiple functions as a fit-to-shape tissue sealant for internal-use of body.

In situ formation of surgical sealants to stop internal fluids leakage is more attractive compared to the traditional suture or staple. However, commercial sealants have weak points in tissue adhesive, cell affinity, antibacterial etc., which make them remain suboptimal for internal use of body. It is required to develop multifunctional sealants that can meet clinical needs. Herein, a PEG-lysozyme (LZM) injectable sealant composed of 4-arm-PEG and lysozyme was developed. Lysozyme offers free amine groups to rapidly cross link with PEG. The hydrogel can tightly adhere to tissues and provide good mechanics to withstand high pressure. Moreover, lysozyme innately confers antibacterial and cell affinity on the hydrogel that are usually lacking in marketed sealants. The hydrogel is easily operated to seal gas or blood leakage in a rabbit trachea and artery defect. Moreover, it can close the transmural left ventricular wall defect on a beating heart. The traumatic organ functions completely recovered postoperatively. Considering the good biocompatibility and the simple fabrication process, the PEG-LZM hydrogel is promising to clinical transformation. More broadly, our work indicates that nature-occurring molecules are versatile building blocks for construction of materials and confer functions, which represents a simple tragedy to develop advanced functional biomaterials.

Evaluation of a simple off-the-shelf bi-layered vascular scaffold based on poly(L-lactide-co-ε-caprolactone)/silk fibroin in vitro and in vivo.

Purpose: In the field of small-caliber vascular scaffold research, excellent vascular remodeling is the key to ensuring anticoagulant function. We prepared an off-the-shelf bi-layered vascular scaffold with a dense inner layer and a loose outer layer and evaluated its remodeling capabilities by in vivo transplantation. Materials and Methods: Based on poly(L-lactide-co-ε-caprolactone) (PLCL), silk fibroin(SF), and heparin (Hep), PLCL/SF/Hep bi-layered scaffolds and PLCL/Hep bi-layered scaffolds were prepared by electrospinning. The inner layer was a PLCL/SF/Hep or PLCL/Hep nanofiber membrane, and the outer layer was PLCL/SF nano yarn. The in vitro tests included a hydrophilicity test, mechanical properties test, and blood and cell compatibility evaluation. The in vivo evaluation was conducted via single rabbit carotid artery replacement and subsequent examinations, including ultrasound imaging, immunoglobulin assays, and tissue section staining. Results: Compared to the PLCL/Hep nanofiber membrane, the hydrophilicity of the PLCL/SF/Hep nanofiber membrane was significantly improved. The mechanical strength met application requirements. Both the blood and cell compatibility were optimal. Most importantly, the PLCL/SF/Hep scaffolds maintained lumen patency for 3 months after carotid artery transplantation in live rabbits. At the same time, CD31 and α-SMA immunofluorescence staining confirmed bionic endothelial and smooth muscle layers remodeling. Conclusion: Using this hybrid strategy, PLCL and SF were combined to manufacture bi-layered small-caliber vascular scaffolds; these PLCL/SF/Hep scaffolds showed satisfactory vascular remodeling.

Tissue-engineered trachea from a 3D-printed scaffold enhances whole-segment tracheal repair in a goat model.

Traditional treatment therapies for tracheal stenosis often cause severe post-operative complications. To solve the current difficulties, novel and more suitable long-term treatments are needed. A whole-segment tissue-engineered trachea (TET) representing the native goat trachea was 3D printed using a poly(caprolactone) (PCL) scaffold engineered with autologous auricular cartilage cells. The TET underwent mechanical analysis followed by in vivo implantations in order to evaluate the clinical feasibility and potential. The 3D-printed scaffolds were successfully cellularized, as observed by scanning electron microscopy. Mechanical force compression studies revealed that both PCL scaffolds and TETs have a more robust compressive strength than does the native trachea. In vivo implantation of TETs in the experimental group resulted in significantly higher mean post-operative survival times, 65.00 ± 24.01 days (n = 5), when compared with the control group, which received autologous trachea grafts, 17.60 ± 3.51 days (n = 5). Although tracheal narrowing was confirmed by bronchoscopy and computed tomography examination in the experimental group, tissue necrosis was only observed in the control group. Furthermore, an encouraging epithelial-like tissue formation was observed in the TETs after transplantation. This large animal study provides potential preclinical evidence around the employment of an orthotopic transplantation of a whole 3D-printed TET.

Electrofabrication of functional materials: Chloramine-based antimicrobial film for infectious wound treatment.

Electrical signals can be imposed with exquisite spatiotemporal control and provide exciting opportunities to create structure and confer function. Here, we report the use of electrical signals to program the fabrication of a chloramine wound dressing with high antimicrobial activity. This method involves two electrofabrication steps: (i) a cathodic electrodeposition of an aminopolysaccharide chitosan triggered by a localized region of high pH; and (ii) an anodic chlorination of the deposited film in the presence of chloride. This electrofabrication process is completed within several minutes and the chlorinated chitosan can be peeled from the electrode to yield a free-standing film. The presence of active NCl species in this electrofabricated film was confirmed with chlorination occurring first on the amine groups and then on the amide groups when large anodic charges were used. Electrofabrication is quantitatively controllable as the cathodic input controls film growth during deposition and the anodic input controls film chlorination. In vitro studies demonstrate that the chlorinated chitosan film has antimicrobial activities that depend on the chlorination degree. In vivo studies with a MRSA infected wound healing model indicate that the chlorinated chitosan film inhibited bacterial growth, induced less inflammation, developed reorganized epithelial and dermis structures, and thus promoted wound healing compared to a bare wound or wound treated with unmodified chitosan. These results demonstrate the fabrication of advanced functional materials (i.e., antimicrobial wound dressings) using controllable electrical signals to both organize structure through non-covalent interactions (i.e., induce chitosan's reversible self-assembly) and to initiate function-conferring covalent modifications (i.e., generate chloramine bonds). Potentially, electrofabrication may provide a simple, low cost and sustainable alternative for materials fabrication. STATEMENT OF SIGNIFICANCE: We believe this work is novel because this is the first report (to our knowledge) that electronic signals enable the fabrication of advanced antimicrobial dressings with controlled structure and biological performance. We believe this work is significant because electrofabrication enables rapid, controllable and sustainable materials construction with reduced adverse environmental impacts while generating high performance materials for healthcare applications. More specifically, we report an electrofbrication of antimicrobial film that can promote wound healing.