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Abstract Treating psoriasis presents a major clinical challenge because of the limitations associated with traditional topical glucocorticoid therapy. This study introduced a drug delivery system utilizing zinc-doped mesoporous silica nanoparticle (Zn-MSN) and microneedle (MN), designed to enhance drug utilization for prolonged anti-inflammatory and anti-itch effects. The MN system facilitated the transdermal delivery of betamethasone dipropionate (BD), allowing its slow release. The BD@Zn-MSN-MN system promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype, achieving superior anti-inflammatory effects compared to the clinically used BD cream. Additionally, this study demonstrated that BD@Zn-MSN-MN could further alleviate itching in psoriasis-afflicted mice by decreasing the excitability of the transient receptor potential vanilloid V1 (TRPV1) ion channel positive neurons and reducing the release of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG). These findings offer new insights and effective therapeutic options for the future design of transdermal drug delivery for psoriasis.

Despite numerous studies on chondrogenesis, the repair of cartilage—particularly the reconstruction of cartilage lacunae through an all-in-one advanced drug delivery system remains limited. In this study, we developed a cartilage lacuna-like hydrogel microsphere system endowed with integrated biological signals, enabling sequential immunomodulation and endogenous articular cartilage regeneration. We first integrated the chondrogenic growth factor transforming growth factor-β3 (TGF-β3) into mesoporous silica nanoparticles (MSNs). Then, TGF-β3@MSNs and insulin-like growth factor 1 (IGF-1) were encapsulated within microspheres made of polydopamine (pDA). In the final step, growth factor-loaded MSN@pDA and a chitosan (CS) hydrogel containing platelet-derived growth factor-BB (PDGF-BB) were blended to produce growth factors loaded composite microspheres (GFs@μS) using microfluidic technology. The presence of pDA reduced the initial acute inflammatory response, and the early, robust release of PDGF-BB aided in attracting endogenous stem cells. Over the subsequent weeks, the continuous release of IGF-1 and TGF-β3 amplified chondrogenesis and matrix formation. μS were incorporated into an acellular cartilage extracellular matrix (ACECM) and combined with a polydopamine-modified polycaprolactone (PCL) structure to produce a tissue-engineered scaffold that mimicked the structure of the cartilage lacunae evenly distributed in the cartilage matrix, resulting in enhanced cartilage repair and patellar cartilage protection. This research provides a strategic pathway for optimizing growth factor delivery and ensuring prolonged microenvironmental remodeling, leading to efficient articular cartilage regeneration.

Abstract Methylmercury (MeHg) in aquatic systems poses a serious public health risk through bioaccumulation in the aquatic food web. In recent years, MeHg has been observed to increase to concerning levels globally in rivers near cities; however, the causes of this increase are not well understood. Here, we demonstrate the significant role of sewage contamination by analyzing over 1,300 publicly available metagenomes in urban rivers worldwide, and conducting experiments with water samples across China. We find that sewage contamination significantly increases the abundance of mercury (Hg)-methylating microorganisms in urban rivers globally. This increase is primarily attributed to the high abundance of active Hg-methylating microorganisms in sewage, which migrate to rivers via direct discharge or combined sewer overflows (CSOs), becoming key contributors to elevated riverine MeHg levels. Our findings underscore the importance of effectively eliminating Hg-methylating microorganisms from sewage to mitigate the public health risks associated with MeHg in urban rivers.

Wastewater treatment plants produce large amounts of sludge requiring stabilization before safe disposal. Traditional biological stabilization approaches are cost-effective but generally require either an extended retention time (10–40 days), or elevated temperatures (40–80 °C) for effective pathogens inactivation. This study overcomes these limitations via a novel acidic aerobic digestion process, leveraging an acid-tolerant ammonia-oxidizing bacterium (AOB) Candidatus Nitrosoglobus. To retain this novel but slowly growing AOB, we proposed the first-ever application of a classical wastewater configuration—moving bed biofilm reactor (MBBR)—for sludge treatment. The AOB in biofilm maintains acidic pH and high nitrite levels in sludge, generating free nitrous acid in situ to expedite sludge stabilization. This process was tested in two laboratory-scale aerobic digesters processing full-scale anaerobically digested sludge. At an ambient temperature of 20 °C, pathogens were reduced to levels well below the threshold specified for the highest stabilization level (Class A), within a retention time of 3.5 days. A high volatile solids reduction of 27.4 ± 5.2% was achieved. Through drastically accelerating stabilization and enhancing reduction, this process substantially saves capital and operational costs for sludge disposal.

Mathematical modeling plays a crucial role in understanding and managing urban water systems (UWS), with mechanistic models often serving as the foundation for their design and operations. Despite the wide adoptions, mechanistic models are challenged by the complexity of dynamic processes and high computational demands. Data-driven models bring opportunities to capture system complexities and reduce computational cost, by leveraging the abundant data made available by recent advance in sensor technologies. However, the interpretability and data availability hinder their wider adoption. This paper advocates for a paradigm shift in the application of data-driven models within the context of UWS. Integrating existing mechanistic knowledge into data-driven modeling offers a unique solution that reduces data requirements and enhances model interpretability. The knowledge-informed approach balances model complexity with dataset size, enabling more efficient and interpretable modeling in UWS. Furthermore, the integration of mechanistic and data-driven models offers a more accurate representation of UWS dynamics, addressing lingering uncertainties and advancing modelling capabilities. This paper presents perspectives and conceptual framework on developing and implementing knowledge-informed data-driven modeling, highlighting their potential to improve UWS management in the digital era.

The biological nitrogen removal process in wastewater treatment inevitably produces nitrous oxide (N2O), a potent greenhouse gas. Coarse bubble mixing is widely employed in wastewater treatment processes to mix anoxic tanks; however, its impacts on N2O emissions are rarely reported. This study investigates the effects of coarse bubble mixing on N2O emissions in a pilot-scale mainstream nitrite shunt reactor over a 50-day steady-state period. Online and offline N2O monitoring campaigns show that coarse bubble mixing in the anoxic zones significantly elevates N2O emissions, yielding an extremely high emission factor of 15.5 ± 3.5 %. Intensive sampling and isotopic analyses suggest that the elevated emissions are primarily due to the inhibition of the N2O denitrification process by oxygen in the anoxic phase introduced by coarse bubbling. Substituting coarse bubble mixing with submersible pump mixing resulted in a substantial reduction of N2O emissions, decreasing the emission factor by an order of magnitude to 1.2 ± 0.8 %. The findings reveal that a previously overlooked factor, coarse bubble mixing, can significantly stimulate N2O emissions. The use of coarse bubble mixing in anoxic tanks of biological nitrogen removal warrants caution.

Accurate diagnosis of sewer inflow and infiltration (I/I) is crucial for ensuring the safe transportation of sewage and the stability of wastewater treatment processes. Identifying periods impacted by I/I is essential for I/I diagnosis, but current methods lack a standard criterion and require adaptation to specific conditions, resulting in low accuracy, complexity, and limited generalizability. This paper proposes a novel approach to distinguish I/I periods from time series of sewer measurements based on anomaly detection theory through an iterative use of a time-series reconstruction model. This method eliminates the need for external data such as rainfalls and avoids intensive manual data analysis. Operating directly on in-sewer data, it enhances accuracy compared to existing approaches and is applicable to various external factors such as rainfall, snowmelt, and seawater intrusion. The method can be applicable to a broad range of monitoring data, including flow rate, temperature, and conductivity. Validated through simulation studies and demonstrated via real-life applications, this method offers an efficient solution for I/I detection, facilitating further I/I diagnosis, including I/I quantification and location identification.

Abstract Integrated urban water management is a well-accepted concept for managing urban water. It requires efficient and integrated technological solutions that enable system-wide gains via a whole-of-system approach. Here, we create a solid link between the manufacturing of an iron salt, its application in an urban water system, and high-quality bioenergy recovery from wastewater. An iron-oxidising electrochemical cell is used to remove CO2 (also H2S and NH3) from biogas, thus achieving biogas upgrading, and simultaneously producing FeCO3. The subsequent dose of the electrochemically produced FeCO3 to wastewater and sludge removes sulfide and phosphate, and enhances sludge settleability and dewaterability, with comparable or superior performance compared to the imported and hazardous iron salts it substitutes (FeCl2, and FeCl3). The process enables water utilities to establish a self-reliant and more secure supply chain to meet its demand for iron salts, at lower economic and environmental costs, and simultaneously achieve recovery of high-quality bioenergy.

Abstract Anaerobic methanotrophic archaea (ANME) carry out anaerobic oxidation of methane, thus playing a crucial role in the methane cycle. Previous genomic evidence indicates that multi-heme c-type cytochromes (MHCs) may facilitate the extracellular electron transfer (EET) from ANME to different electron sinks. Here, we provide experimental evidence supporting cytochrome-mediated EET for the reduction of metals and electrodes by ‘Candidatus Methanoperedens nitroreducens’, an ANME acclimated to nitrate reduction. Ferrous iron-targeted fluorescent assays, metatranscriptomics, and single-cell imaging suggest that ‘Ca. M. nitroreducens’ uses surface-localized redox-active cytochromes for metal reduction. Electrochemical and Raman spectroscopic analyses also support the involvement of c-type cytochrome-mediated EET for electrode reduction. Furthermore, several genes encoding menaquinone cytochrome type-c oxidoreductases and extracellular MHCs are differentially expressed when different electron acceptors are used.

Abstract Successful biomaterial implantation requires appropriate immune responses. Macrophages are key mediators involved in this process. Currently, exploitation of the intrinsic properties of biomaterials to modulate macrophages and immune responses is appealing. In this study, we prepared hydrophilic nanofibers with an aligned topography by incorporating polyethylene glycol and polycaprolactone using axial electrospinning. We investigated the effect of the nanofibers on macrophage behavior and the underlying mechanisms. With the increase of hydrophilicity of aligned nanofibers, the inflammatory gene expression of macrophages adhering to them was downregulated, and M2 polarization was induced. We further presented clear evidence that the inflammasome NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was the cellular sensor by which macrophages sense the biomaterials, and it acted as a regulator of the macrophage-mediated response to foreign bodies and implant integration. In vivo, we showed that the fibers shaped the implant-related immune microenvironment and ameliorated peritendinous adhesions. In conclusion, our study demonstrated that hydrophilic aligned nanofibers exhibited better biocompatibility and immunological properties.

Anaerobic microorganisms can oxidize short-chain gaseous alkanes such as ethane, propane and butane using sulfate as electron acceptor. Here, the authors show that a bioreactor enrichment of a wastewater microbial community can perform anaerobic propane oxidation coupled to nitrate reduction.

As the wastewater sector moves towards achieving net zero greenhouse gas (GHG) emissions, quantifying and understanding fugitive emissions from various sewage treatment steps is crucial for developing effective GHG abatement strategies. Methane (CH4) emissions from a sludge drying pan (SDP) were measured at a wastewater treatment plant in Australia for more than a year, using a micrometeorological technique paired with open-path lasers. The emission rate was tightly associated with sludge additions, climatology, and operational processes. The mean emission rate during the 90 weeks after initial sludge addition was 2.3 (± 0.8) g m−2 d−1, with cumulative emissions of approximately 32 t of CH4. A dynamic temporal pattern of emissions was observed, highlighting the importance of continuous (or near-continuous) measurements for quantifying SDP emissions. A Methane Correction Factor (MCF) expressed as a fraction of the measured chemical oxygen demand of the sludge, was determined to be 0.17 after 63 weeks (the median operational cycle duration at the facility). This is broadly consistent with, albeit slightly less than, the IPCC default value of 0.2 for shallow anaerobic lagoons. These emission measurements will support wastewater utilities that employ open air sludge drying processes to develop effective GHG abatement strategies.

Mainstream nitrogen removal via anammox is widely recognized as a promising wastewater treatment process. However, its application is challenging at large scale due to unstable suppression of nitrite-oxidizing bacteria (NOB). In this study, a pilot-scale mainstream anammox process was implemented in an Integrated Fixed-film Activated Sludge (IFAS) configuration. Stable operation with robust NOB suppression was maintained for over one year. This was achieved through integration of three key control strategies: i) low dissolved oxygen (DO = 0.4 ± 0.2 mg O2/L), ii) regular free nitrous acid (FNA)-based sludge treatment, and iii) residual ammonium concentration control (NH4+ with a setpoint of ∼8 mg N/L). Activity tests and FISH demonstrated that NOB barely survived in sludge flocs and were inhibited in biofilms. Despite receiving organic-deficient wastewater from a pilot-scale High-Rate Activated Sludge (HRAS) system as the feed, the system maintained a stable effluent total nitrogen concentration mostly below 10 mg N/L, which was attributed to the successful retention of anammox bacteria. This study successfully demonstrated large-scale long-term mainstream anammox application and generated new practical knowledge for NOB control and anammox retention.

Objective: The treatment of cartilage lesions has always been a difficult problem. Although cartilage tissue engineering provides alternative treatment options for cartilage lesions, biodegradable tissue engineering scaffolds have limitations. Methods: In this study, we constructed a porous PEEK scaffold via 3D printing, surface-engineered with concentrated sulfuric acid for 15 s (SPK-15), 30 s (SPK-30), and 60 s (SPK-60). We systematically evaluated the physical and chemical characteristics and biofunctionalities of the scaffolds, and then evaluated the macrophage polarization modulating ability and anti-inflammatory effects of the sulfonated PEEK, and observed the cartilage-protective effect of SPK using a co-culture study. We further evaluated the repair effect of PEEK and SPK by implanting the prosthetic scaffold into a cartilage defect in a rabbit model. Results: Compared to the PEEK, SPK-15 and SPK-60 scaffolds, SPK-30 has a good micro/nanostructure, appropriate biomechanical properties (compressive modulus, 43 ± 5 MPa; Shaw hardness, 20.6 ± 1.3 HD; close to native cartilage, 30 ± 8 MPa, 17.8 ± 0.8 HD), and superior biofunctionalities. Compared to PEEK, sulfonated PEEK can favor macrophage polarization to the M2 phenotype, which increases anti-inflammatory cytokine secretion. Furthermore, SPK can also prevent macrophage-induced cartilage degeneration. The in-vivo animal experiment demonstrates that SPK can favor new tissue ingrowth and integration, prevent peri-scaffold cartilage degeneration and patellar cartilage degeneration, inhibit inflammatory cytokine secretion, and promote cartilage function restoration. Conclusion: The present study confirmed that the 3D printed porous sulfonated PEEK scaffold could promote cartilage functional repair, and suggests a new promising strategy for treating cartilage defects with a functional prosthesis that spontaneously inhibits nearby cartilage degeneration. Translational potential of this article: In the present study, we propose a new cartilage repair strategy based on a porous, non-biodegradable polyetheretherketone (PEEK) scaffold, which may bring up a new treatment route for elderly patients with cartilage lesions in the future.

Tendon injuries often result in significant pain and disability and impose severe clinical and financial burdens on our society. Despite considerable achievements in the field of regenerative medicine in the past several decades, effective treatments remain a challenge due to the limited natural healing capacity of tendons caused by poor cell density and vascularization. The development of tissue engineering has provided more promising results in regenerating tendon-like tissues with compositional, structural and functional characteristics comparable to those of native tendon tissues. Tissue engineering is the discipline of regenerative medicine that aims to restore the physiological functions of tissues by using a combination of cells and materials, as well as suitable biochemical and physicochemical factors. In this review, following a discussion of tendon structure, injury and healing, we aim to elucidate the current strategies (biomaterials, scaffold fabrication techniques, cells, biological adjuncts, mechanical loading and bioreactors, and the role of macrophage polarization in tendon regeneration), challenges and future directions in the field of tendon tissue engineering.

The potential of artificial intelligence (AI) in water management is widely recognised by research and practice communities alike, with an increasing number of applications showed tackling water supply, stormwater and wastewater management challenges. However, there is a critical knowledge gap in understanding the fundamental role of AI in the development of urban water infrastructure (UWI). This review aimed to provide an analysis of how AI could be aligned to support the future development of UWI systems. Four types of AI analytics – descriptive, diagnostic, predictive and prescriptive – are discussed and linked to the improvement in the performance of UWI systems from three categories: reliability, resilience and sustainability. It is envisioned that AI technology will play a pivotal role in UWI transitioning to the future through underpinning the five development pathways: decentralisation, circular economy, greening, decarbonisation and automation. The barriers in improving AI adoption in the real world are also highlighted from four dimensions: cyber-physical infrastructure, institutional governance, social-economic systems and technological development in wider society. Embedding AI in the development pathways and tackling the barriers can ensure that AI-empowered systems are deployed in an equitable and responsible way to improve the resilience and sustainability of future UWI systems.

Despite intensive effort was made to regenerate injured meniscus by cell-free strategies through recruiting endogenous stem/progenitor cells, meniscus regeneration remains a great challenge in clinic. In this study, we found decellularized meniscal extracellular matrix (MECM) preserved native meniscal collagen and glycosaminoglycans which could be a good endogenous regeneration guider for stem cells. Moreover, MECM significantly promoted meniscal fibrochondrocytes viability and proliferation, increased the expression of type II collagen and proteoglycans in vitro. Meanwhile, we designed 3D-printed polycaprolactone (PCL) scaffolds which mimic the circumferential and radial collagen orientation in native meniscus. Taken these two advantages together, a micro-structure and micro-environment dually biomimetic cell-free scaffold was manipulated. This cell-free PCL-MECM scaffold displayed superior biocompatibility and yielded favorable biomechanical capacities closely to native meniscus. Strikingly, neo-menisci were regenerated within PCL-MECM scaffolds which were transplanted into knee joints underwent medial meniscectomy in rabbits and sheep models. Histological staining confirmed neo-menisci showed meniscus-like heterogeneous staining. Mankin scores showed PCL-MECM scaffold could protect articular cartilage well, and knee X-ray examination revealed same results. Knee magnetic resonance imaging (MRI) scanning also showed some neo-menisci in PCL-MECM scaffold group. In conclusion, PCL-MECM scaffold appears to optimize meniscus regeneration. This could represent a promising approach worthy of further investigation in preclinical applications.

Implant-associated infection (IAI) and insufficient implant osseointegration are two primary concerns of implant failure. Polyetheretherketone (PEEK), though widely used in orthopedic implants, has been limited in clinical applications by its poor osteogenic activity, inferior antibacterial ability, and improper immunological reactions. In this study, copper (Cu), a multi-functional bioactive ion, is incorporated into the polydopamine (PDA) coating on PEEK surfaces using a metal-catecholamine assembling strategy. This DA-CuII coating induces a spatial distribution of Cu, exerting biological functions simultaneously through passive contact and active release of Cu. DA-CuII coated PEEK surfaces exhibit not only superior abilities of osteogenesis, angiogenesis, and antibiosis but also possess immunomodulatory effects to enhance macrophages-mediated osteogenesis and antibacterial activity. Moreover, the DA-CuII coated PEEK induces a mild and necessary inflammatory response, exhibiting excellent antibacterial ability and superior osseointegration. Our findings suggest that DA-CuII coated PEEK has excellent potential for orthopedic implants and provides new insight into novel modification strategies of PEEK materials.

In China, the sewerage system plays an essential role in antibiotic removal; however, the fate profiles of antibiotics in sewers are not well understood, and risk identification throughout the sewerage system is inadequate. Based on the extensive detection results for typical groups of antibiotics in the discharge sources, influent and effluent from wastewater treatment plants (WWTPs), and excess sludge, a comprehensive evaluation was conducted to reveal the elimination profiles of the antibiotics, identify the fate characteristics in both sewers and WWTPs, assess the exposure risk levels, and propose a control strategy. The total concentration (based on the median concentrations of the target antibiotics) in aqueous waters was estimated to decrease from 7383.4 ng/L at the discharge source to 886.6 ng/L in the WWTP effluent, among which 69.6% was reduced by sewers and 18.4% was reduced by WWTPs. Antibiotic reduction in sewers was a combined effect of dilution, physiochemical reactions, sorption, biodegradation, and retransformation, and the A2O-MBR + ozonation process in the WWTPs exhibited superior performance in diminishing antibiotics. Notably, accumulated antibiotics in the excess sludge posed a high risk to natural environments (with a risk quotient of approximately 13.0), and the potential risk during combined sewer overflows (CSOs) was undetermined. Thus, enhanced sludge treatment techniques, accurate risk prediction, and proper precautions at CSOs are required to mitigate potential risk. A novel scheme involving an accurate estimation of discharge loads, preliminary treatment of highly concentrated discharge sources, and synergic control in sewers was proposed to eliminate antibiotics at the front end of pipes.

Abstract Reconstruction of the knee meniscus remains a significant clinical challenge owing to its complex anisotropic tissue organization, complex functions, and limited healing capacity in the inner region. The development of in situ tissue‐engineered meniscal scaffolds, which provide biochemical signaling to direct endogenous stem/progenitor cell (ESPC) behavior, has the potential to revolutionize meniscal tissue engineering. In this study, a fiber‐reinforced porous scaffold was developed based on aptamer Apt19S‐mediated mesenchymal stem cell (MSC)‐specific recruitment and dual growth factor (GF)‐enhanced meniscal differentiation. The aptamer, which can specifically recognize and recruit MSCs, was first chemically conjugated to the decellularized meniscus extracellular matrix (MECM) and then mixed with gelatin methacrylate (GelMA) to form a photocrosslinkable hydrogel. Second, connective tissue growth factor (CTGF)‐loaded poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) and transforming growth factor‐β3 (TGF‐β3)‐loaded PLGA microparticles (MPs) were mixed with aptamer‐conjugated MECM to simulate anisotropic meniscal regeneration. These three bioactive molecules were delivered sequentially. Apt19S, which exhibited high binding affinity to synovium‐derived MSCs (SMSCs), was quickly released to facilitate the mobilization of ESPCs. CTGF incorporated within PLGA NPs was released rapidly, inducing profibrogenic differentiation, while sustained release of TGF‐β3 in PLGA MPs remodeled the fibrous matrix into fibrocartilaginous matrix. The in vitro results showed that the sequential release of Apt19S/GFs promoted cell migration, proliferation, and fibrocartilaginous differentiation. The in vivo results demonstrated that the sequential release system of Apt/GF‐scaffolds increased neomeniscal formation in rabbit critical‐sized meniscectomies. Thus, the novel delivery system shows potential for guiding meniscal regeneration in situ.

Tissue engineering provides a promising avenue for treating cartilage defects. However, great challenges remain in the development of structurally and functionally optimized scaffolds for cartilage repair and regeneration. In this study, decellularized cartilage extracellular matrix (ECM) and waterborne polyurethane (WPU) were employed to construct WPU and WPU-ECM scaffolds by water-based 3D printing using low-temperature deposition manufacturing (LDM) system, which combines rapid deposition manufacturing with phase separation techniques. The scaffolds successfully achieved hierarchical macro‐microporous structures. After adding ECM, WPU scaffolds were markedly optimized in terms of porosity, hydrophilia and bioactive components. Moreover, the optimized WPU-ECM scaffolds were found to be more suitable for cell distribution, adhesion, and proliferation than the WPU scaffolds. Most importantly, the WPU-ECM scaffold could facilitate the production of glycosaminoglycan (GAG) and collagen and the upregulation of cartilage-specific genes. These results indicated that the WPU-ECM scaffold with hierarchical macro‐microporous structures could recreate a favorable microenvironment for cell adhesion, proliferation, differentiation, and ECM production. In vivo studies further revealed that the hierarchical macro‐microporous WPU-ECM scaffold combined with the microfracture procedure successfully regenerated hyaline cartilage in a rabbit model. Six months after implantation, the repaired cartilage showed a similar histological structure and mechanical performance to that of normal cartilage. In conclusion, the hierarchical macro‐microporous WPU-ECM scaffold may be a promising candidate for cartilage tissue engineering applications in the future.

The treatment of bone defects in weight-bearing areas is mainly to transplant filling materials into the defect area, to provide immediate and strong support for weight-bearing. At present, the commonly used filling material is bone cement, which can only provide physical support without bone regeneration effect. The long-term stress at the interface may cause the loosening of bone cement. The ideal filling material should provide not only strong mechanical support but also promote bone regeneration. We introduce a 3D printing frame-filling structure in this study. The structure was printed with polylactic acid/bioactive glass as the frame, and bone cement as the filler. In this system, bone cement was used to provide immediate fixation, and the frame provided long-term fixation by promoting osteogenic induction and conduction between the interface. The results showed that the degradation of bioactive glass in the frame promoted osteogenic metabolism, induced M2 polarization of macrophages, and inhibited local inflammatory response. The in vivo study revealed that implantation of the frame-filling structure significantly promoted bone regeneration in the femoral bone defect area of New Zealand white rabbits. For a bone defect in a weight-bearing area, long-term stability could be obtained by bone integration through this frame-filling structure.

Fibrocartilaginous regeneration at the tendon-to-bone interface is a major challenge for rotator cuff tear repair. We fabricated a decellularized umbilical cord Wharton’s jelly (DUCWJ) scaffold by decellularization method and performed histological and proteomic analyses. We then synthesized a kartogenin-conjugated DUCWJ (DUCWJ-KGN) scaffold using an EDC/NHS catalyst. 1H NMR, Fluorescence staining, and FTIR confirmed that the carboxyl group of KGN was covalently coupled with the free amine groups in the Wharton’s jelly (WJ) matrix, and the in vitro release profiles of KGN from the DUCWJ-KGN scaffold showed sustained release for 6 weeks. Both the DUCWJ and DUCWJ-KGN scaffolds had excellent biocompatibility and biofunctionality, supporting cell attachment, migration, and proliferation, and DUCWJ-KGN scaffolds the KGN-loaded scaffold could induce higher chondrogenic markers expression. The DUCWJ-KGN scaffold could also promote fibrocartilaginous regeneration at the rotator cuff tendon-to-bone interface, which indicates that the DUCWJ-KGN scaffold is a promising enthesis to enhance fibrocartilaginous interface regeneration.

Background: The use of partial articular resurfacing surgery with a mini-implant has been gradually increasing; the implant is mainly made of cobalt–chromium metal material, and cartilage changes cannot be monitored after implantation. Thus, we aimed to develop a novel local articular resurfacing polyetheretherketone (PEEK) mini-implant and investigate its feasibility for postoperative magnetic resonance imaging (MRI) monitoring of implant location, bone changes, and cartilage degeneration without artefacts. Methods: Nine skeletally mature female standardised goats were used and divided into the sham, PEEK, and cobalt–chromium–molybdenum alloy (Co–Cr–Mo) groups. The animals underwent local articular resurfacing operation with Co–Cr–Mo alloy (Co–Cr–Mo group) and PEEK (PEEK group) mini-implants. X-ray, computed tomography, and MRI examinations were performed at 12 weeks postoperatively. The sham group underwent a similar surgical procedure to expose the femoral head but without implantation. Gross necropsy and surface topography measurement of the articular cartilage of the acetabulum were performed after sacrificing the animals. Imaging artefacts and opposing cartilage degeneration in the acetabulum were also examined. Results: Cartilage damage occurred in both the Co–Cr–Mo and PEEK groups, and the damaged cartilage area was markedly larger in the Co–Cr–Mo group than in the PEEK group, as assessed by gross necropsy and histological staining. The mean surface roughness of the opposing cartilage was approximately 65.3, 117.4, and 188.4 ​μm ​at 12 weeks in the sham, PEEK, and Co–Cr–Mo groups, respectively. The Co–Cr–Mo mini-implant was visualised on radiographs, but computed tomography and MR images were markedly affected by artefacts, whereas the opposing cartilage and surrounding tissue were clear on MR images in the PEEK group. Opposing cartilage damage and subchondral bone marrow oedema could be detected by MRI in the PEEK group. Conclusions: The PEEK mini-implant can be a novel alternative to the Co–Cr–Mo mini-implant in articular resurfacing to treat focal osteochondral defects with less cartilage damage. It is feasible to postoperatively monitor the PEEK implant location, surrounding bone changes, and opposing cartilage degeneration by MRI without artefacts. The translational potential of this article: The use of MRI to monitor changes in the opposing cartilage after prosthesis implantation has not been widely applied because MR images are generally affected by artefacts generated by the metal prosthesis. This study revealed that the PEEK mini-implant can be a novel alternative to the Co–Cr–Mo mini-implant in articular resurfacing to treat focal osteochondral defects, and it is feasible to monitor the PEEK implant location, surrounding bone changes, and opposing cartilage damage/degeneration by MRI without artefacts postoperatively.

Anaerobic methanotrophic (ANME) archaea can drive anaerobic oxidation of methane (AOM) using solid iron or manganese oxides as the electron acceptors, hypothetically via direct extracellular electron transfer (EET). This study investigated the response of Candidatus “Methanoperedens nitroreducens TS” (type strain), an ANME archaeon previously characterized to perform nitrate-dependent AOM, to an Fe(III)-amended condition over a prolonged period. Simultaneous consumption of methane and production of dissolved Fe(II) were observed for more than 500 days in the presence of Ca. “M. nitroreducens TS,” indicating that this archaeon can carry out Fe(III)-dependent AOM for a long period. Ca. “M. nitroreducens TS” possesses multiple multiheme c-type cytochromes (MHCs), suggesting that it may have the capability to reduce Fe(III) via EET. Intriguingly, most of these MHCs are orthologous to those identified in Candidatus “Methanoperedens ferrireducens,” an Fe(III)-reducing ANME archaeon. In contrast, the population of Ca. “M. nitroreducens TS” declined and was eventually replaced by Ca. “M. ferrireducens,” implying niche differentiation between these two ANME archaea in the environment.

Abstract Background Bioelectrochemical methane oxidation catalysed by anaerobic methanotrophic archaea (ANME) is constrained by limited methane bioavailability as well as by slow kinetics of extracellular electron transfer (EET) of ANME. In this study, we tested a combination of two strategies to improve the performance of methane-driven bioelectrochemical systems that includes (1) the use of hollow fibre membranes (HFMs) for efficient methane delivery to the ANME organisms and (2) the amendment of ferricyanide, an effective soluble redox mediator, to the liquid medium to enable electrochemical bridging between the ANME organisms and the anode, as well as to promote EET kinetics of ANME. Results The combined use of HFMs and the soluble mediator increased the performance of ANME-based bioelectrochemical methane oxidation, enabling the delivery of up to 196 mA m−2, thereby outperforming the control system by 244 times when HFMs were pressurized at 1.6 bar. Conclusions Improving methane delivery and EET are critical to enhance the performance of bioelectrochemical methane oxidation. This work demonstrates that by process engineering optimization, energy recovery from methane through its direct oxidation at relevant rates is feasible.

Osteochondral lesions represent a major clinical challenge, especially in the elderly. Traditional treatment strategies, such as arthroplasty or tissue engineering, have limitations and drawbacks. In this study, we presented a new treatment concept for the application of an innovative porous bioactive prosthesis with regenerative activity for the treatment of osteoarticular lesions. For regenerative activity, we fabricated chitosan/mesoporous silica nanoparticles (CS/MSNs) composite microspheres via the microfluidic method as a dual-factor carrier for the sequential release of platelet-derived growth factor BB (PDGF-BB) and kartogenin (KGN). We then integrated the factor carrier and a nondegradable polyetheretherketone (PEEK) scaffold through a surface modification technique to construct the porous sulfonated PEEK (SPK) @polydopamine (polydopamine)-CS/MSNs scaffold. We systematically evaluated the biocompatibility and biofunctionality of the SPK@PDA-CS/MSNs scaffold and implanted the scaffold in an in vivo cartilage defect model in rabbits. These results suggest that the SPK@PDA-CS/MSNs scaffold is biocompatible, promotes cell migration, enhances chondrogenic differentiation of BMSCs in vitro, and promotes cartilage regeneration in vivo. The porous bioactive prosthesis with regenerative activity presented first in this study may comprise a new therapeutic concept for osteoarticular lesions.

BackgroundTotal knee arthroplasty (TKA) is now frequently performed and is highly successful. However, patient satisfaction after TKA is often difficult to achieve. Because of the presence of metallic prosthetic knee joints, there is a lack of imaging tools that can accurately assess the patient's postoperative prosthetic position, soft tissue impingement, and periprosthetic bone density after TKA. We conducted a clinical trial of the world's first totally modular polyetheretherketone (PEEK) TKA and determined the bone density values in the stress concentration area around the prosthesis based on postoperative computed tomography data to reconstruct a three-dimensional model of the PEEK prosthetic knee joint after implantation. Based on the model, the overhang of the prosthesis was measured at various locations on the prosthesis.MethodsAll patients who underwent PEEK-based TKA were postoperatively assessed with radiography and computed tomography (CT). Hounsfield units (HUs) for the different components of the quantitative CT assessment were measured separately.ResultsTen patients (nine female and one male) aged 59–74 (mean 66.9, median 67) years were included. The HU values were as follows: PEEK prosthesis mean 182.95, standard deviation (SD) 4.90, coefficient of variation (CV) 2.68; polyethylene mean −89.41, SD 4.14, CV −4.63; lateral femoral osteochondral mean 192.19, SD 55.05, CV 28.64; lateral tibial osteochondral mean 122.94, SD 62.14, CV 42.86; medial femoral osteophyte mean 180.76, SD 43.48, CV 24.05; and medial tibial osteophyte mean 282.59, SD 69.28, CV 24.52. Analysis of the data at 1, 3, and 6 months showed that the mean PE (p = 0.598) and PEEK (p = 0.916) measurements did not change with the time of measurement. There was a decrease in bone mineral density in the lateral tibia at 3 months (p = 0.044). Otherwise, there was no significant change in bone density in other regions (p = 0.124–0.803). There was no overhang in all femoral prostheses, whereas there were two cases of overhang in tibial prostheses. Overhang measurements do not differ significantly across time points. The overhang measurements were not significantly different at all time points (p = 0.186–0.967).ConclusionPEEK knee joint prosthesis has excellent CT compatibility. The change in periprosthetic bone volume during the follow-up period can be determined using the HU value after CT scan, while the prosthesis position can be assessed. This assessment may potentially guide future improvements in knee prosthesis alignment techniques and artificial knee prosthesis designs.

Knee menisci are structurally complex components that preserve appropriate biomechanics of the knee. Meniscal tissue is susceptible to injury and cannot heal spontaneously from most pathologies, especially considering the limited regenerative capacity of the inner avascular region. Conventional clinical treatments span from conservative therapy to meniscus implantation, all with limitations. There have been advances in meniscal tissue engineering and regenerative medicine in terms of potential combinations of polymeric biomaterials, endogenous cells and stimuli, resulting in innovative strategies. Recently, polymeric scaffolds have provided researchers with a powerful instrument to rationally support the requirements for meniscal tissue regeneration, ranging from an ideal architecture to biocompatibility and bioactivity. However, multiple challenges involving the anisotropic structure, sophisticated regenerative process, and challenging healing environment of the meniscus still create barriers to clinical application. Advances in scaffold manufacturing technology, temporal regulation of molecular signaling and investigation of host immunoresponses to scaffolds in tissue engineering provide alternative strategies, and studies have shed light on this field. Accordingly, this review aims to summarize the current polymers used to fabricate meniscal scaffolds and their applications in vivo and in vitro to evaluate their potential utility in meniscal tissue engineering. Recent progress on combinations of two or more types of polymers is described, with a focus on advanced strategies associated with technologies and immune compatibility and tunability. Finally, we discuss the current challenges and future prospects for regenerating injured meniscal tissues.

The spread of antibiotic resistance has become a major concern for public health. As emerging contaminants, various metallic nanoparticles (NPs) and ionic heavy metals have been ubiquitously detected in various environments. Although previous studies have indicated NPs and ionic heavy metals could exhibit co-selection effects for antibiotic resistance, little is known about whether and how they could promote antibiotic resistance spread via horizontal gene transfer across bacterial genera. This study, we report both CuO NPs and copper ions (Cu2+) could stimulate the conjugative transfer of multiple-drug resistance genes. When exposing bacteria to CuO NPs or Cu2+ at environmental-relevant and sub-inhibitory concentrations (e.g., 1–100 μmol/L), conjugation frequencies of plasmid-encoded antibiotic resistance genes across genera (i.e., from Escherichia coli to Pseudomonas putida) were significantly enhanced (p

The widespread use of CuO nanoparticles (NPs) results in their continuous release into the environment, which could pose risks to public health and to microbial ecosystems. Following consumption, NPs will initially enter into sewer systems and interact with and potentially influence sewer microbial communities. An understanding of the response of microbes in sewers, particularly sulfate-reducing bacteria (SRB), to the CuO NPs induced stress is important as hydrogen sulfide produced by SRB can cause sewer corrosion and odour emissions. In this study, we elucidated how the anabolic and catabolic processes of a model SRB, Desulfovibrio vulgaris Hidenborough (D. vulgaris), respond to CuO NPs. Physiological analyses indicated that the exposure of the culture to CuO NPs at elevated concentrations (>50 mg/L) inhibited both its anabolic and catabolic activities, as revealed by lowered cell proliferation and sulfate reduction rate. The antibacterial effects of CuO NPs were mainly attributed to the overproduction of reactive oxygen species. Transcriptomic analysis indicated that genes encoding for flagellar assembly and some genes involved in electron transfer and respiration were down-regulated, while genes for the ferric uptake regulator (Fur) were up-regulated. Moreover, the CuO NPs exposure significantly up-regulated genes involved in protein synthesis and ATP synthesis. These results suggest that CuO NPs inhibited energy conversion, cell mobility, and iron starvation to D. vulgaris. Meanwhile, D. vulgaris attempted to respond to the stress of CuO NPs by increasing protein and ATP synthesis. These findings offer new insights into the bacterial-nanoparticles interaction at the transcriptional level, and advance our understanding of impacts of CuO NPs on SRB in the environment. Keywords: CuO nanoparticles, Ecotoxicity, Sulfate-reducing bacteria, Genome-wide RNA sequencing

Background: Antibiotic resistance poses an increasing threat to public health. Horizontal gene transfer (HGT) promoted by antibiotics is recognized as a significant pathway to disseminate antibiotic resistance genes (ARGs). However, it is unclear whether non-antibiotic, anti-microbial (NAAM) chemicals can directly promote HGT of ARGs in the environment. Objectives: We aimed to investigate whether triclosan (TCS), a widely-used NAAM chemical in personal care products, is able to stimulate the conjugative transfer of antibiotic multi-resistance genes carried by plasmid within and across bacterial genera. Methods: We established two model mating systems, to investigate intra-genera transfer and inter-genera transfer. Escherichia coli K-12 LE392 carrying IncP-α plasmid RP4 was used as the donor, and E. coli K-12 MG1655 or Pseudomonas putida KT2440 were the intra- and inter-genera recipients, respectively. The mechanisms of the HGT promoted by TCS were unveiled by detecting oxidative stress and cell membrane permeability, in combination with Nanopore sequencing, genome-wide RNA sequencing and proteomic analyses. Results: Exposure of the bacteria to environmentally relevant concentrations of TCS (from 0.02 μg/L to 20 μg/L) significantly stimulated the conjugative transfer of plasmid-encoded multi-resistance genes within and across genera. The TCS exposure promoted ROS generation and damaged bacterial membrane, and caused increased expression of the SOS response regulatory genes umuC, dinB and dinD in the donor. In addition, higher expression levels of ATP synthesis encoding genes in E. coli and P. putida were found with increased TCS dosage. Conclusions: TCS could enhance the conjugative ARGs transfer between bacteria by triggering ROS overproduction at environmentally relevant concentrations. These findings improve our awareness of the hidden risks of NAAM chemicals on the spread of antibiotic resistance. Keywords: Non-antibiotic antimicrobial (NAAM), Triclosan, Environmental concentration, Antibiotic resistance genes, Horizontal gene transfer

Meniscus tissue engineering (MTE) aims to fabricate ideal scaffolds to stimulate the microenvironment for recreating the damaged meniscal tissue. Indeed, favorable mechanical properties, suitable biocompatibility, and inherent chondrogenic capability are crucial in MTE. In this study, we present a composite scaffold by 3D printing a poly(ε-caprolactone) (PCL) scaffold as backbone, followed by injection with the meniscus extracellular matrix (MECM), and modification with kartogenin (KGN)-loaded poly(lactic-co-glycolic) acid (PLGA) microsphere (μS), which serves as a drug delivery system. Therefore, we propose a plan to improve meniscus regeneration via KGN released from the 3D porous PCL/MECM scaffold. The final results showed that the hydrophilicity and bioactivity of the resulting PCL/MECM scaffold were remarkably enhanced. In vitro synovium-derived mesenchymal stem cells (SMSCs) experiments suggested that introducing MECM components helped cell adhesion and proliferation and maintained promising ability to induce cell migration. Moreover, KGN-incorporating PLGA microspheres, which were loaded on scaffolds, showed a prolonged release profile and improved the chondrogenic differentiation of SMSCs during the 14-day culture. Particularly, the PCL/MECM-KGN μS seeded by SMSCs showed the highest secretion of total collagen and aggrecan. More importantly, the synergistic effect of the MECM and sustained release of KGN can endow the PCL/MECM-KGN μS scaffolds with not only excellent cell affinity and cell vitality preservation but also chondrogenic activity. Thus, the PCL/MECM-KGN μS scaffolds are expected to have good application prospects in the field of MTE.

It remains scientifically challenging to regenerate injured cartilage in orthopedics. Recently, an endogenous cell recruitment strategy based on a combination of acellular scaffolds and chemoattractants to specifically and effectively recruit host cells and promote chondrogenic differentiation has brought new hope for in situ articular cartilage regeneration. In this study, a transforming growth factor-β3 (TGF-β3)-loaded biomimetic natural scaffold based on demineralized cancellous bone (DCB) and acellular cartilage extracellular matrix (ECM) was developed and found to improve chondral repair by enhancing cell migration and chondrogenesis. The DCB/ECM scaffold has porous microstructures (pore size: 67.76 ± 8.95 μm; porosity: 71.04 ± 1.62%), allowing the prolonged release of TGF-β3 (up to 50% after 42 days in vitro) and infrapatellar fat pad adipose-derived stem cells (IPFSCs) that maintain high cell viability (>96%) and favorable cell distribution and phenotype after seeding onto the DCB/ECM scaffold. The DCB/ECM scaffold itself can also provide a sustained release system to effectively promote IPFSC migration (nearly twofold in vitro). Moreover, TGF-β3 loaded on scaffolds showed enhanced chondrogenic differentiation (such as collagen II, ACAN, and SOX9) of IPFSCs after 3 weeks of culture. After implanting the composite scaffold into the knee joints of rabbits, enhanced chondrogenic differentiation was discovered at 1, 2, and 4 weeks post-surgery, and improved repair of cartilage defects in terms of biochemical, biomechanical, radiological, and histological results was identified at 3 and 6 months post-implantation. To conclude, our study demonstrates that the growth factor (GF)-loaded scaffold can facilitate cell homing, migration, and chondrogenic differentiation and promote the reconstructive effects of in vivo cartilage formation, revealing that this staged regeneration strategy combined with endogenous cell recruitment and pro-chondrogenesis is promising for in situ articular cartilage regeneration.

Methane is an abundant low-carbon fuel that provides a valuable energy resource, but it is also a potent greenhouse gas. Therefore, anaerobic oxidation of methane (AOM) is an essential process with central features in controlling the carbon cycle. Candidatus ‘Methanoperedens nitroreducens’ (M. nitroreducens) is a recently discovered methanotrophic archaeon capable of performing AOM via a reverse methanogenesis pathway utilizing nitrate as the terminal electron acceptor. Recently, reverse methanogenic pathways and energy metabolism among anaerobic methane-oxidizing archaea (ANME) have gained significant interest. However, the energetics and the mechanism for electron transport in nitrate-dependent AOM performed by M. nitroreducens is unclear. This paper presents a genome-scale metabolic model of M. nitroreducens, iMN22HE, which contains 813 reactions and 684 metabolites. The model describes its cellular metabolism and can quantitatively predict its growth phenotypes. The essentiality of the cytoplasmic heterodisulfide reductase HdrABC in the reverse methanogenesis pathway is examined by modeling the electron transfer direction and the specific energy-coupling mechanism. Furthermore, based on better understanding electron transport by modeling, a new energy transfer mechanism is suggested. The new mechanism involves reactions capable of driving the endergonic reactions in nitrate-dependent AOM, including the step reactions in reverse canonical methanogenesis and the novel electron-confurcating reaction HdrABC. The genome metabolic model not only provides an in silico tool for understanding the fundamental metabolism of ANME but also helps to better understand the reverse methanogenesis energetics and its thermodynamic feasibility.

Emissions of hydrogen sulfide and methane are two of the major concerns in sewers, causing corrosion, odour and health problems. This study proposed a new free ammonia (FA)-based approach for controlling the biological production of sulfide and methane in sewers. This is based on the discovery that the FA contained in urine wastewater is strongly biocidal to anaerobic sewer biofilms. Long-term operation of two laboratory sewer reactors, with one being dosed with urine wastewater and the other being dosed with raw sewage as a control, revealed the effectiveness of the proposed FA approach. The results showed that dosing of real urine wastewater at FA concentration of 154 mg NH3-N/L with exposure for 24 h immediately reduced over 80% sulfide and methane in the experimental sewer reactor, while the time for recovering 50% sulfide and methane production were 6 days and 28 days, respectively. It also showed that intermittent dosing with an interval time of 5–15 days reduced around 60% sulfide on average. As suggested by community analysis, the remaining sulfide might be produced by a sulfate-reducing bacterial genus Desulfobulbus. Collectively, urine is a part of municipal sewage, and thus separation and re-dosing of the urine wastewater into the sewer for sulfide and methane control should enable the minimization of operational costs and environmental impacts, compared with the previous dosing of chemicals.

An innovative process coupling anaerobic ammonium oxidation (anammox) with nitrite/nitrate-dependent anaerobic methane oxidation (n-DAMO) in membrane biofilm reactors (MBfRs) has been developed to achieve high-level nitrogen removal from both sidestream (i.e., anaerobic digestion liquor) and mainstream (i.e., domestic strength) wastewater. In this study, a 1D biofilm model embedding the n-DAMO and anammox reactions was developed to facilitate further understanding of the process and its optimization. The model was calibrated and validated using comprehensive data sets from two independent MBfRs, treating sidestream- and mainstream-strength wastewater, respectively. Modelling results revealed a unique biofilm stratification. While anammox bacteria dominated throughout the biofilm, n-DAMO archaea (coupling nitrate reduction with anaerobic methane oxidation) only occurred at the inner layer and n-DAMO bacteria (coupling nitrite reduction with anaerobic methane oxidation) spread more evenly with a slightly higher fraction in the outer layer. The established MBfRs were robust against dynamic influent flowrates and nitrite/ammonium ratios. Thicker biofilms were beneficial for not only the total nitrogen (TN) removal but also the system robustness. Additionally, a positive correlation between the nitrogen removal efficiency and the residual methane emission was observed, as a result of higher methane partial pressure required. However, there was a threshold of methane partial pressure, above which the residual methane increased but nitrogen removal efficiency was stable. Meanwhile, thicker biofilms were also favorable to achieve less residual methane emission. Simulation results also suggested the feasibility of methane-based MBfRs to polish mainstream anammox effluent to meet a stringent N discharge standard (e.g., TN

The data in this article mainly present the sequences of activated sludge from a full-scale municipal wastewater treatment plant (WWTP) carrying out simultaneous nitrogen and phosphorous removal in Beijing, China. Data include the operational conditions and performance, dominant microbes and taxonomic analysis in this WWTP, and function annotation results based on SEED, Clusters of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Sequencing data were generated by using Illumina HiSeq. 2000 platform according to the recommendations of the manufacturer. The sequencing data have been deposited in MG-RAST server (project ID: mgm4735473.3). For more information, see âUnraveling microbial structure and diversity of activated sludge in a full-scale simultaneous nitrogen and phosphorus removal plant using metagenomic sequencingâ by Guo et al. (2017) [1].

The cross-flow rotating packed bed (RPB) has attracted wide attention in recent years because of its advantages of large gas capacity, low pressure drop and lack of flooding limitation. However, the complex structure of the packing makes it difficult to obtain the gas flow characteristics in the cross-flow RPB by experiments. In this study, the dry pressure drop in the cross-flow RPB was investigated by computational fluid dynamics (CFD). The packing was modeled by the porous media model and the rotation of the packing was simulated by the sliding mesh model. The simulation results obtained by three turbulence models were compared with experimental results, and the RNG k-ε model was found to best describe the turbulence behaviors in the cross-flow RPB. Then, the effects of gas flow rate and rotating speed on dry pressure drop in different parts of the cross-flow RPB were analyzed. The results of this study can provide important insights into the design and scale-up of cross-flow RPB.

Cartilage lesions can lead to progressive cartilage degeneration; moreover, they involve the subchondral bone, resulting in osteoarthritis (OA) onset and progression. Bioactive glasses, with the dual function of supporting both bone and cartilage regeneration, have become a promising biomaterial for cartilage/bone engineering applications. This is especially true for those containing therapeutic ions, which act as ion delivery systems and may further promote cartilage repair. In this study, we successfully fabricated Mg-containing bioactive glass nanospheres (Mg-BGNs) and constructed three different scaffolds, DCECM, Mg-BGNs-1/DCECM (1% Mg-BGNs), and Mg-BGNs-2/DCECM (10% Mg-BGNs) scaffold, by incorporating Mg-BGNs into decellularized cartilage extracellular matrix (DCECM). All three scaffolds showed favorable microarchitectural and ion controlled-release properties within the ideal range of pore size for tissue engineering applications. Furthermore, all scaffolds showed excellent biocompatibility and no signs of toxicity. Most importantly, the addition of Mg-BGNs to the DCECM scaffolds significantly promoted cell proliferation and enhanced chondrogenic differentiation induction of mesenchymal stem cells (MSCs) in pellet culture in a dose-dependent manner. Collectively, the multifunctional Mg-BGNs/DCECM composite scaffold not only demonstrated biocompatibility but also a significant chondrogenic response. Our study suggests that the Mg-BGNs/DCECM composite scaffold would be a promising tissue engineering tool for osteochondral lesions, with the ability to simultaneously stimulate articular cartilage and subchondral bone regeneration.

Abstract The intensive applications of silver nanoparticles (AgNPs) inevitably cause continuous release of such materials into environments, as a consequence posing potential risks to microbial communities in engineered or natural ecosystems. However, the magnitude of antibacterial capacity of nanoparticles is still inconclusive, owing to influential factors such as the size of nanoparticle, microbial species, or environmental conditions. To reveal whether the presence of air would alter AgNPs ecotoxicity, Pseudomonas aeruginosa PAO1, a facultative denitrifying bacterium and an opportunity pathogen, was used to study antibacterial assays under both anaerobic and aerobic conditions. The results indicate that the respiration status of P. aeruginosa affect the ecotoxicity of AgNPs. P. aeruginosa cultured under aerobic condition were more susceptible to AgNPs than that under anaerobic condition. Aerobic condition greatly enhanced bacteriostatic effects of AgNPs but not their bactericidal effects, as the ratio of viable but nonculturable (VBNC) bacteria remained above 90% when 5 mg L−1 AgNPs applied. Our findings offer further understanding for the degree of toxicity of nanoparticles on microbial ecosystems and underscore the importance of exposure condition (e.g. oxygen) in the mode of action of AgNPs.

Integrating denitrifying anaerobic methane oxidation (DAMO) with Anammox provides alternative solutions to simultaneously remove nitrogen and mitigate methane emission from wastewater treatment. However, the practical application of DAMO has been greatly limited by slow-growing DAMO microorganisms living on low-solubility gaseous methane. In this work, DAMO and Anammox co-cultures were fast enriched using high concentration of mixed sludges from various environments, and achieved nitrogen removal rate of 76.7 mg NH4+-N L−1 d−1 and 87.9 mg NO3−-N L−1 d−1 on Day 178. Subsequently, nitrogen removal rate significantly decreased but recovered quickly through increasing methane flushing frequency, indicating methane availability could be the limiting factor of DAMO activity. Thus, this work developed a novel Membrane Aerated Membrane Bioreactor (MAMBR), which equipped with gas permeable membrane for efficient methane delivery and ultrafiltration membrane for complete biomass retention. After inoculated with enriched sludge, nitrogen removal rates of MAMBR were significantly enhanced to 126.9 mg NH4+-N L−1 d−1 and 158.8 mg NO3−-N L−1 d−1 by membrane aeration in batch test. Finally, the MAMBR was continuously fed with synthetic wastewater containing ammonium and nitrite to mimic the effluent from partial nitritation. When steady state with nitrogen loading rate of 2500 mg N L−1 d−1 was reached, the MAMBR achieved total nitrogen removal of 2496.7 mg N L−1 d−1, with negligible nitrate in effluent (~6.5 mg NO3−-N L−1). 16S rRNA amplicon sequencing and fluorescence in situ hybridization revealed the microbial community dynamics during enrichment and application. The high performance of nitrogen removal (2.5 kg N m−3 d−1) within 200 days operation and excellent biomass retention capacity (8.67 kg VSS m−3) makes the MAMBR promising for practical application of DAMO and Anammox in wastewater treatment. Keywords: Nitrogen removal, Anammox, Denitrifying anaerobic methane oxidation, Membrane aerated membrane bioreactor, Application

It has been reported that microbial reduction of sulfate, nitrite/nitrate and iron/manganese could be coupled with anaerobic oxidation of methane (AOM), which plays a significant role in controlling methane emission from anoxic niches. However, little is known about microbial chromate (Cr(VI)) reduction coupling with AOM. In this study, a microbial consortium was enriched via switching nitrate dosing to chromate feeding as the sole electron acceptor under anaerobic condition in a membrane biofilm reactor (MBfR), in which methane was continuously provided as the electron donor through bubble-less hollow fiber membranes. According to long-term reactor operation and chromium speciation analysis, soluble chromate could be reduced into Cr(III) compounds by using methane as electron donor. Fluorescence in situ hybridization and high-throughput 16S rRNA gene amplicon profiling further indicated that after feeding chromate Candidatus ‘Methanoperedens’ (a known nitrate-dependent anaerobic methane oxidation archaeon) became sole anaerobic methanotroph in the biofilm, potentially responsible for the chromate bio-reduction driven by methane. Two potential pathways of the microbial AOM-coupled chromate reduction were proposed: (i) Candidatus ‘Methanoperedens’ independently utilizes chromate as electron acceptor to form Cr(III) compounds, or (ii) Candidatus ‘Methanoperedens’ oxidizes methane to generate intermediates or electrons, which will be utilized to reduce chromate to Cr(III) compounds by unknown chromate reducers synergistically. Our findings suggest a possible link between the biogeochemical chromium and methane cycles. Keywords: Microbial chromate reduction, Anaerobic oxidation of methane, Cr(III) compounds, Candidatus ‘Methanoperedens’, Membrane biofilm reactor

Articular cartilage lacks a blood supply and nerves. Hence, articular cartilage regeneration remains a major challenge in orthopedics. Decellularized extracellular matrix- (ECM-) based strategies have recently received particular attention. The structure of native cartilage exhibits complex zonal heterogeneity. Specifically, the development of a tissue-engineered scaffold mimicking the aligned structure of native cartilage would be of great utility in terms of cartilage regeneration. Previously, we fabricated oriented PLGA/ACECM (natural, nanofibrous, articular cartilage ECM) composite scaffolds. In vitro, we found that the scaffolds not only guided seeded cells to proliferate in an aligned manner but also exhibited high biomechanical strength. To detect whether oriented cartilage regeneration was possible in vivo, we used mesenchymal stem cell (MSC)/scaffold constructs to repair cartilage defects. The results showed that cartilage defects could be completely regenerated. Histologically, these became filled with hyaline cartilage and subchondral bone. Moreover, the aligned structure of cartilage was regenerated and was similar to that of native tissue. In conclusion, the MSC/scaffold constructs enhanced the structure-specific regeneration of hyaline cartilage in a rabbit model and may be a promising treatment strategy for the repair of human cartilage defects.

The meniscus plays a vital role in protecting the articular cartilage of the knee joint. The inner two-thirds of the meniscus are avascular, and injuries to this region often fail to heal without intervention. The use of tissue engineering and regenerative medicine techniques may offer novel and effective approaches to repairing meniscal injuries. Meniscal tissue engineering and regenerative medicine typically use one of two techniques, cell-based or cell-free. While numerous cell-based strategies have been applied to repair and regenerate meniscal defects, these techniques possess certain limitations including cellular contamination and an increased risk of disease transmission. Cell-free strategies attempt to repair and regenerate the injured tissues by recruiting endogenous stem/progenitor cells. Cell-free strategies avoid several of the disadvantages of cell-based techniques and, therefore, may have a wider clinical application. This review first compares cell-based to cell-free techniques. Next, it summarizes potential sources for endogenous stem/progenitor cells. Finally, it discusses important recruitment factors for meniscal repair and regeneration. In conclusion, cell-free techniques, which focus on the recruitment of endogenous stem and progenitor cells, are growing in efficacy and may play a critical role in the future of meniscal repair and regeneration.

The histological features of cartilage call attention to the fact that cartilage has a little capacity to repair itself owing to the lack of a blood supply, nerves, or lymphangion. Stem cells have emerged as a promising option in the field of cartilage tissue engineering and regenerative medicine and could lead to cartilage repair. Much research has examined cartilage regeneration utilizing stem cells. However, both the potential and the limitations of this procedure remain controversial. This review presents a summary of emerging trends with regard to using stem cells in cartilage tissue engineering and regenerative medicine. In particular, it focuses on the characterization of cartilage stem cells, the chondrogenic differentiation of stem cells, and the various strategies and approaches involving stem cells that have been used in cartilage repair and clinical studies. Based on the research into chondrocyte and stem cell technologies, this review discusses the damage and repair of cartilage and the clinical application of stem cells, with a view to increasing our systematic understanding of the application of stem cells in cartilage regeneration; additionally, several advanced strategies for cartilage repair are discussed.

The meniscus plays a crucial role in maintaining knee joint homoeostasis. Meniscal lesions are relatively common in the knee joint and are typically categorized into various types. However, it is difficult for inner avascular meniscal lesions to self-heal. Untreated meniscal lesions lead to meniscal extrusions in the long-term and gradually trigger the development of knee osteoarthritis (OA). The relationship between meniscal lesions and knee OA is complex. Partial meniscectomy, which is the primary method to treat a meniscal injury, only relieves short-term pain; however, it does not prevent the development of knee OA. Similarly, other current therapeutic strategies have intrinsic limitations in clinical practice. Tissue engineering technology will probably address this challenge by reconstructing a meniscus possessing an integrated configuration with competent biomechanical capacity. This review describes normal structure and biomechanical characteristics of the meniscus, discusses the relationship between meniscal lesions and knee OA, and summarizes the classifications and corresponding treatment strategies for meniscal lesions to understand meniscal regeneration from physiological and pathological perspectives. Last, we present current advances in meniscal scaffolds and provide a number of prospects that will potentially benefit the development of meniscal regeneration methods.