Regenerative Strategies Research Articles

Promotion of osteochondral repair through immune microenvironment regulation and activation of endogenous chondrogenesis via the release of apoptotic vesicles from donor MSCs

Utilizing transplanted human umbilical cord mesenchymal stem cells (HUMSCs) for cartilage defects yielded advanced tissue regeneration, but the underlying mechanism remain elucidated. Early after HUMSCs delivery to the defects, we observed substantial apoptosis. The released apoptotic vesicles (apoVs) of HUMSCs promoted cartilage regeneration by alleviating the chondro-immune microenvironment. ApoVs triggered M2 polarization in macrophages while simultaneously facilitating the chondrogenic differentiation of endogenous MSCs. Mechanistically, in macrophages, miR-100-5p delivered by apoVs activated the MAPK/ERK signaling pathway to promote M2 polarization. In MSCs, let-7i-5p delivered by apoVs promoted chondrogenic differentiation by targeting the eEF2K/p38 MAPK axis. Consequently, a cell-free cartilage regeneration strategy using apoVs combined with a decellularized cartilage extracellular matrix (DCM) scaffold effectively promoted the regeneration of osteochondral defects. Overall, new mechanisms of cartilage regeneration by transplanted MSCs were unconcealed in this study. Moreover, we provided a novel experimental basis for cell-free tissue engineering-based cartilage regeneration utilizing apoVs.

Extracellular Vesicles from Compression-Loaded Cementoblasts Promote the Tissue Repair Function of Macrophages.

Treatment strategies for hard tissue defects aim to establish a mineralized microenvironment that facilitates tissue remodeling. As a mineralized tissue, cementum shares a similar structure with bone and exhibits an excellent capacity to resist resorption under compression. Macrophages are crucial for mineralized remodeling; however, their functional alterations in the microenvironment of cementum remain poorly understood. Therefore, this study explores the mechanisms by which cementum resists resorption under compression and the regulatory roles of cementoblasts in macrophage functions. As a result, extracellular vesicles from compression-loaded cementoblasts (Comp-EVs) promote macrophage M2 polarization and enhance the clearance of apoptotic cells (efferocytosis) by 2- to 3-fold. Local injection of Comp-EVs relieves cementum destruction in mouse root resorption model by activating the tissue repair function of macrophages. Moreover, Comp-EV-loaded hydrogels achieve significant bone healing in calvarial bone defect. Unexpectedly, under compression, EV secretion in cementoblasts is reduced by half. RNA-Seq analysis and verification reveal that Rab35 expression decreases by 60% under compression, thereby hampering the release of EVs. Rab35 overexpression is proposed as a modification of cementoblasts to boost the yield of Comp-EVs. Collectively, Comp-EVs activate the repair function of macrophages, which will be a potential therapeutic strategy for hard tissue repair and regeneration.

A tacrolimus-eluting nerve guidance conduit enhances regeneration in acritical-sized peripheral nerve injury rat model.

Critical-sized peripheral nerve injuries pose a significant clinical challenge and lead to functional loss and disability. Current regeneration strategies, including autografts, synthetic nerve conduits, and biologic treatments, encounter challenges such as limited availability, donor site morbidity, suboptimal recovery, potential immune responses, and sustained stability and bioactivity. An obstacle in peripheral nerve regeneration is the immune response that can lead to inflammation and scarring that impede the regenerative process. Addressing both the immunological and regenerative needs is crucial for successful nerve recovery. Here, we introduce a novel biodegradable tacrolimus-eluting nerve guidance conduit engineered from a blend of poly (L-lactide-co-caprolactone) to facilitate peripheral nerve regeneration and report the testing of this conduit in 15-mm critical-sized gaps in the sciatic nerve of rats. The conduit's diffusion holes enable the local release of tacrolimus, a potent immunosuppressant with neuro-regenerative properties, directly into the injury site. A series of in vitro experiments were conducted to assess the ability of the conduit to maintain a controlled tacrolimus release profile that could promote neurite outgrowth. Subsequent in vivo assessments in rat models of sciatic nerve injury revealed significant enhancements in nerve regeneration, as evidenced by improved axonal growth and functional recovery compared to controls using placebo conduits. These findings indicate the synergistic effects of combining a biodegradable conduit with localized, sustained delivery of tacrolimus, suggesting a promising approach for treating peripheral nerve injuries. Further optimization of the design and long-term efficacy studies and clinical trials are needed before the potential for clinical translation in humans can be considered.

Nanoclay-Composite Hydrogels for Bone Tissue Engineering.

Nanoclay-composite hydrogels represent a promising avenue for advancing bone tissue engineering. Traditional hydrogels face challenges in providing mechanical strength, biocompatibility, and bioactivity necessary for successful bone regeneration. The incorporation of nanoclay into hydrogel matrices offers a potential unique solution to these challenges. This review provides a comprehensive overview of the fabrication, physico-chemical/biological performance, and applications of nanoclay-composite hydrogels in bone tissue engineering. Various fabrication techniques, including in situ polymerization, physical blending, and 3D printing, are discussed. In vitro and in vivo studies evaluating biocompatibility and bioactivity have demonstrated the potential of these hydrogels for promoting cell adhesion, proliferation, and differentiation. Their applications in bone defect repair, osteochondral tissue engineering and drug delivery are also explored. Despite their potential in bone tissue engineering, nanoclay-composite hydrogels face challenges such as optimal dispersion, scalability, biocompatibility, long-term stability, regulatory approval, and integration with emerging technologies to achieve clinical application. Future research directions need to focus on refining fabrication techniques, enhancing understanding of biological interactions, and advancing towards clinical translation and commercialization. Overall, nanoclay-composite hydrogels offer exciting opportunities for improving bone regeneration strategies.

The synergistic effect of polyphenols and polypeptides for plant-based bioplastic film – Enhanced UV resistance, antioxidant and antibacterial performance

The exceptional biodegradability and active biological functions of bio-based packaging materials have attracted increasing interest. In this study, a bioplastic film was developed by introducing simultaneously polyphenols (tea polyphenols, TPs) and peptides (nisin) into a soy protein isolate/sodium alginate (SPI/SA) based film-forming matrix. The research results revealed that the dynamic coordinated interaction between TPs and nisin enhanced mechanical properties, UV-resistance, and thermal stability of bioplastic films. Furthermore, the bioplastic film exhibited antibacterial activity and antioxidant properties. Significantly, biofilm growth of Staphylococcus aureus treated with TPs-5/Nisin-5 bioplastic film was inhibited by 91.12% compared to the blank group. The shelf life of beef with TPs-5/Nisin-5 bioplastic film was prolonged by 2 days because of the synergistic effect of TPs and nisin. Additionally, the bioplastic film biodegraded in the natural environment about 21 days. This environmentally friendly regeneration strategy and the integration of advantageous functions provided ideas for the development of active food packaging.

Endogenous Tissue Engineering for Chondral and Osteochondral Regeneration: Strategies and Mechanisms.

Increasing attention has been paid to the development of effective strategies for articular cartilage (AC) and osteochondral (OC) regeneration due to their limited self-reparative capacities and the shortage of timely and appropriate clinical treatments. Traditional cell-dependent tissue engineering faces various challenges such as restricted cell sources, phenotypic alterations, and immune rejection. In contrast, endogenous tissue engineering represents a promising alternative, leveraging acellular biomaterials to guide endogenous cells to the injury site and stimulate their intrinsic regenerative potential. This review provides a comprehensive overview of recent advancements in endogenous tissue engineering strategies for AC and OC regeneration, with a focus on the tissue engineering triad comprising endogenous stem/progenitor cells (ESPCs), scaffolds, and biomolecules. Multiple types of ESPCs present within the AC and OC microenvironment, including bone marrow-derived mesenchymal stem cells (BMSCs), adipose-derived mesenchymal stem cells (AD-MSCs), synovial membrane-derived mesenchymal stem cells (SM-MSCs), and AC-derived stem/progenitor cells (CSPCs), exhibit the ability to migrate toward injury sites and demonstrate pro-regenerative properties. The fabrication and characteristics of scaffolds in various formats including hydrogels, porous sponges, electrospun fibers, particles, films, multilayer scaffolds, bioceramics, and bioglass, highlighting their suitability for AC and OC repair, are systemically summarized. Furthermore, the review emphasizes the pivotal role of biomolecules in facilitating ESPCs migration, adhesion, chondrogenesis, osteogenesis, as well as regulating inflammation, aging, and hypertrophy-critical processes for endogenous AC and OC regeneration. Insights into the applications of endogenous tissue engineering strategies for in vivo AC and OC regeneration are provided along with a discussion on future perspectives to enhance regenerative outcomes.

The Guidance of Public Value in China’s Historic Environment: Research on Regeneration Strategies Using Taiyuan’s Bell Tower Street as an Example

When profit-driven renewal is difficult to implement, many historic districts in China become “frozen” under protection. In the recent social context of “building cities for the people”, public value-oriented renewal of urban historic areas has become crucial in city transformation. This study investigates strategies for historic district regeneration in China by integrating spatial form, urban governance, and public value. We propose a novel framework to analyze the regeneration of historic districts, using Taiyuan’s Bell Tower Street as a case study. The framework distinguishes between two dimensions: spatial and economic–social. In the spatial dimension, we focus on the transformation of spatial form to regenerate public value, emphasizing the attribute of “publicness” as central to urban regeneration efforts. This involves a tiered approach to excavating and upgrading historic districts at macro, meso, and micro levels. The economic–social dimension explores urban governance to enhance public value through collaboration between government, market, and societal actors. This study employs a mixed-methods approach, including document reviews, interviews, field observations, and statistical data analysis. The analysis highlights that a public value-oriented approach to heritage regeneration can balance historical preservation with contemporary urban needs, offering a sustainable model for other cities.

Effects of Synthetic Toll-Like Receptor 9 Ligand Molecules on Pulpal Immunomodulatory Response and Repair after Injuries.

Synthetic oligodeoxynucleotides (ODNs) containing unmethylated cytosine-phosphate-guanine (CpG) motifs (CpG-ODNs) are ligand molecules for Toll-like receptor 9 (TLR9), which is expressed by odontoblasts in vitro and dental pulp cells. This study determined the effects of CpG-ODNs on pulpal immunomodulatory response and repair following injury. Briefly, the upper right first molars of three-week-old mice were extracted, immersed in Type A (D35) or B (K3) CpG-ODN solutions (0.1 or 0.8 mM) for 30 min, and then replanted. Pulpal healing and immunomodulatory activity were assessed by hematoxylin-eosin and AZAN staining, as well as immunohistochemistry. One week following the operation, inflammatory reactions occurred in all of the experimental groups; however, re-revascularization and newly formed hard tissue deposition were observed in the pulp chamber of all groups at week 2. A positive trend in the expression of immune cell markers was observed toward the CpG-ODN groups at 0.1 mM. Our data suggest that synthetic CpG-ODN solutions at low concentrations may evoke a long-lasting macrophage-TLR9-mediated pro-inflammatory, rather than anti-inflammatory, response in the dental pulp to modulate the repair process and hard tissue formation. Further studies are needed to determine the effects of current immunomodulatory agents in vitro and in vivo and develop treatment strategies for dental tissue regeneration.

An improved grey wolf optimization algorithm based on scale-free network topology

The grey wolf optimizer is a novel intelligent optimization algorithm that has become popular due to its low number of parameters, fast convergence speed, and simplicity. However, the classical algorithm, with its update strategy allowing wolves to learn only from the alpha wolves, often leads to premature convergence and lower convergence accuracy. Therefore, in this paper, an improved grey wolf optimization algorithm based on scale-free network topology (SFGWO) is proposed to address these issues. The improved algorithm first employs a strategy for formulating a population based on a scale-free network topology, where interaction between wolves is limited to topological neighbors, which helps enhance the exploration capabilities of the algorithm. Second, a neighbor learning strategy is introduced to capture individual diversity, facilitating the solution space exploration. Finally, an adaptive individual regeneration strategy is adopted to balance the exploration and exploitation processes and reduce the risk of falling into local optima. The proposed algorithm is evaluated through simulation experiments using 23 classical and the CEC2019 benchmark functions. The experimental results demonstrate that the SFGWO algorithm excels in terms of solution accuracy and exploration capabilities. The applicability and effectiveness of the SFGWO algorithm are further validated through testing on three practical engineering problems.

Propelling Minimally Invasive Tissue Regeneration With Next-Era Injectable Pre-Formed Scaffolds.

The growing aging population, with its associated chronic diseases, underscores the urgency for effective tissue regeneration strategies. Biomaterials play a pivotal role in the realm of tissue reconstruction and regeneration, with a distinct shift toward minimally invasive (MI) treatments. This transition, fueled by engineered biomaterials, steers away from invasive surgical procedures to embrace approaches offering reduced trauma, accelerated recovery, and cost-effectiveness. In the realm of MI tissue repair and cargo delivery, various techniques are explored. While in situ polymerization is prominent, it is not without its challenges. This narrative review explores diverse biomaterials, fabrication methods, and biofunctionalization for injectable pre-formed scaffolds, focusing on their unique advantages. The injectable pre-formed scaffolds, exhibiting compressibility, controlled injection, and maintained mechanical integrity, emerge as promising alternative solutions to in situ polymerization challenges. The conclusion of this review emphasizes the importance of interdisciplinary design facilitated by synergizing fields of materials science, advanced 3D biomanufacturing, mechanobiological studies, and innovative approaches for effective MI tissue regeneration.

Sapling recruitment as an indicator of carbon resiliency in forests of the northern USA.

Tree regeneration shapes forest carbon dynamics by determining long-term forest composition and structure, which suggests that threats to natural regeneration may diminish the capacity of forests to replace live tree carbon transferred to the atmosphere or other pools through tree mortality. Yet, the potential implications of tree regeneration patterns for future carbon dynamics have been sparsely studied. We used forest inventory plots to investigate whether the composition of existing tree regeneration is consistent with aboveground carbon stock loss, replacement, or gain for forests across the northeastern and midwestern USA, leveraging a recently developed method to predict the likelihood of sapling recruitment from seedling abundance tallied within six seedling height classes. A comparison of carbon stock predictions from tree and seedling composition suggested that 29% of plots were poised to lose carbon based on seedling composition, 55% were poised for replacement of carbon stocks (<5 Mg ha-1 difference) and 16% were poised to gain carbon. Forests predicted to lose carbon tended to be on steeper slopes, at lower latitudes, and in rolling upland environments. Although plots predicted to gain and lose carbon had similar stand ages, carbon loss plots had greater current carbon stocks. Synthesis and applications. Our results demonstrate the utility of considering tree regeneration through the lens of carbon replacement to develop effective management strategies to secure long-term carbon storage and resilience in the context of global change. Forests poised to lose C due to climate change and other stressors could be prioritized for regeneration strategies that enhance long-term carbon resilience and stewardship.

Navigating Preclinical Models and Medications for Peripheral Neuropathy: A Review.

Peripheral neuropathy (PN) is a multifaceted disorder characterised by peripheral nerve damage, manifesting in symptoms like pain, weakness, and autonomic dysfunction. This review assesses preclinical models in PN research, evaluating their relevance to human disease and their role in therapeutic development. The Streptozotocin (STZ)-induced diabetic rat model is widely used to simulate diabetic neuropathy but has limitations in faithfully replicating disease onset and progression. Cisplatin-induced PN models are suitable for studying chemotherapy-induced peripheral neuropathy (CIPN) and closely resemble human pathology. However, they may not fully replicate the spectrum of sensory and motor deficits. Paclitaxel-induced models also contribute to understanding CIPN mechanisms and testing neuroprotective agents. Surgical or trauma-induced models offer insights into nerve regeneration and repair strategies. Medications such as gabapentin, pregabalin, duloxetine, and fluoxetine have demonstrated promise in these models, enhancing our understanding of their therapeutic efficacy. Despite progress, developing models that accurately mirror human PN remains imperative due to its complex nature. Continuous refinement and innovative approaches are critical for effective drug discovery. This review underscores the strengths and limitations of current models and advocates for an integrated approach to address the complexities of PN better and optimise treatment outcomes.

Assessment of Tie2-Rejuvenated Nucleus Pulposus Cell Transplants from Young and Old Patient Sources Demonstrates That Age Still Matters.

Cell transplantation is being actively explored as a regenerative therapy for discogenic back pain. This study explored the regenerative potential of Tie2+ nucleus pulposus progenitor cells (NPPCs) from intervertebral disc (IVD) tissues derived from young (<25 years of age) and old (>60 years of age) patient donors. We employed an optimized culture method to maintain Tie2 expression in NP cells from both donor categories. Our study revealed similar Tie2 positivity rates regardless of donor types following cell culture. Nevertheless, clear differences were also found, such as the emergence of significantly higher (3.6-fold) GD2 positivity and reduced (2.7-fold) proliferation potential for older donors compared to young sources. Our results suggest that, despite obtaining a high fraction of Tie2+ NP cells, cells from older donors were already committed to a more mature phenotype. These disparities translated into functional differences, influencing colony formation, extracellular matrix production, and in vivo regenerative potential. This study underscores the importance of considering age-related factors in NPPC-based therapies for disc degeneration. Further investigation into the genetic and epigenetic alterations of Tie2+ NP cells from older donors is crucial for refining regenerative strategies. These findings shed light on Tie2+ NPPCs as a promising cell source for IVD regeneration while emphasizing the need for comprehensive understanding and scalability considerations in culture methods for broader clinical applicability.

A Regenerative Coking‐resistant CO2 Hydrogenation Reactor using a Protonic Ceramic Electrolysis Cell with Thin and Robust Fuel Electrode

AbstractA CO2 hydrogenation reactor based on protonic ceramic electrolysis cells (PCECs) is one of the most promising options for the efficient and clean conversion of CO2. However, insufficient performance and durability have hindered the practical application of such CO2 hydrogenation reactors. Here, fabricates a large‐area (≈10 cm2) tubular air electrode supported PCEC (AES‐PCEC) and develop a fuel electrode regeneration strategy for efficient and durable CO2 hydrogenation. The AES‐PCEC demonstrates a CO yield of 2.88 mL min−1 at 650 °C while maintaining excellent durability for over 1100 h. The high stability of the AES‐PCEC can be attributed to the robust and thin fuel electrode structure as well as the water‐mediated carbon removal regeneration mechanism. Density functional theory calculations have confirmed the regeneration mechanism facilitated by the excellent water hydration and dissociation capability of the BaCe0.4Zr0.4Y0.1Yb0.1O3‐σ. This work offers a feasible strategy to design high‐performance and durable PCEC‐based CO2 hydrogenation reactors.

Urban Regeneration of Old Neighborhoods: The Case of Old Al Ghanim in Doha, Qatar

ABSTRACT Qatar witnessed its first urban expansion era following economic prosperity amid the discovery and production of oil and its exportation in the early 1950s. However, the capital city of Qatar, Doha, beheld numerous challenges following the rapid growth that resulted in unsystematic urban sprawl in the city. Therefore, the country developed national expansion plans and policies for the geographical city change process by encouraging sustainable and regenerative approaches. Studies concentrating on urban regeneration in rapidly growing cities offer prospects by evaluating existing settings and proposing regeneration solutions. This research aims to assess the urban environment of an old neighborhood in Doha, called Fareej Al Ghanim by examining the existing conditions and providing recommendations for its regeneration. A qualitative research methodology is applied in this study to identify proper solutions for urban regeneration in Fareej Al Ghanim. The latter is an important case to analyze, study and recommend an appropriate regeneration strategy, which can be used as an example of best practice for other historic neighborhoods in Qatar, the Gulf and elsewhere. Namely, the urban regeneration of Old Al Ghanim neighborhood in Doha was studied through physical analysis of (A) urban settings (B) land uses and (C) current building conditions. The information was collected through data collection, site visits, walking tour assessments and map analyses. The findings identified the following; (1) poor infrastructure of the neighborhood, (2) multiple abandoned buildings in a deteriorating state, (3) lack of parking spaces and over congestion, (4) absence of cycling paths and pavements and (5) inexistence of open areas where people can sit and relax. Thus, the proposed recommendations for urban regeneration are based on (A) enhancing the physical environment of the area through land-use changes and (B) rehabilitating the surviving historic buildings and reconstructing the deteriorating ones. The findings offer policymakers, city planners, and designers an opportunity to improve old districts in Qatar, the Gulf and elsewhere.

Comparative Analysis and Regeneration Strategies for Three Types of Cartilage.

Cartilage tissue, encompassing hyaline cartilage, fibrocartilage, and elastic cartilage, plays a pivotal role in the human body because of its unique composition, structure, and biomechanical properties. However, the inherent avascularity and limited regenerative capacity of cartilage present significant challenges to its healing following injury. This review provides a comprehensive analysis of the current state of cartilage tissue engineering, focusing on the critical components of cell sources, scaffolds, and growth factors tailored to the regeneration of each cartilage type. We explore the similarities and differences in the composition, structure, and biomechanical properties of the three cartilage types and their implications for tissue engineering. A significant emphasis is placed on innovative strategies for cartilage regeneration, including the potential for in situ transformation of cartilage types through microenvironmental manipulation, which may offer novel avenues for repair and rehabilitation. The review underscores the necessity of a nuanced approach to cartilage tissue engineering, recognizing the distinct requirements of each cartilage type while exploring the potential of transforming one cartilage type into another as a flexible and adaptive repair strategy. Through this detailed examination, we aim to broaden the understanding of cartilage tissue engineering and inspire further research and development in this promising field.

Glucosamine sulfate-loaded nanofiber reinforced carboxymethyl chitosan sponge for articular cartilage restoration

Cartilage is severely limited in self-repair after damage, and tissue engineering scaffold transplantation is considered the most promising strategy for cartilage regeneration. However, scaffolds without cells and growth factors, which can effectively avoid long cell culture times, high risk of infection, and susceptibility to contamination, remain scarce. Hence, we developed a cell- and growth factor-dual free hierarchically structured nanofibrous sponge to mimic the extracellular matrix, in which the encapsulated core–shell nanofibers served both as mechanical supports and as long-lasting carriers for bioactive biomass molecules (glucosamine sulfate). Under the protection of the nanofibers in this designed sponge, glucosamine sulfate could be released continuously for at least 30 days, which significantly accelerated the repair of cartilage tissue in a rat cartilage defect model. Moreover, the nanofibrous sponge based on carboxymethyl chitosan as the framework could effectively fill irregular cartilage defects, adapt to the dynamic changes during cartilage movement, and maintain almost 100 % elasticity even after multiple compression cycles. This strategy, which combines fiber freeze-shaping technology with a controlled-release method for encapsulating bioactivity, allows for the assembly of porous bionic scaffolds with hierarchical nanofiber structure, providing a novel and safe approach to tissue repair.

Mitigating lipopolysaccharide-induced impairment in human dental pulp stem cells with tideglusib-doped nanoparticles: Enhancing osteogenic differentiation and mineralization

ObjectiveDrug-loaded non-resorbable polymeric nanoparticles (NPs) are proposed as an adjunctive treatment for pulp regenerative strategies. The present in vitro investigation aimed to evaluate the effectiveness of tideglusib-doped nanoparticles (TDg-NPs) in mitigating the adverse effects of bacterial lipopolysaccharide endotoxin (LPS) on the viability, morphology, migration, differentiation and mineralization potential of human dental pulp stem cells (hDPSCs). MethodsCell viability, proliferation, and differentiation were assessed using a MTT assay, cell migration evaluation, cell cytoskeleton staining analysis, Alizarin Red S staining and expression of the odontogenic related genes by a real-time quantitative polymerase chain reaction (RT-qPCR) were also performed. Cells were tested both with and without stimulation with LPS at various time points. One-way ANOVA and Tukey's test were employed for statistical analysis (p < 0.05). ResultsAdequate cell viability was encountered in all groups and at every tested time point (24, 48, 72 and 168 h), without differences among the groups (p > 0.05). The analysis of cell cytoskeleton showed nuclear alteration in cultures with undoped NPs after LPS stimulation. These cells exhibited an in blue diffuse and multifocal appearance. Some nuclei looked fragmented and condensed. hDPSCs after LPS stimulation but in the presence of TDg-NPs exhibited less nuclei changes. LPS induced down-regulation of Alkaline phosphatase, Osteonectin and Collagen1 gene markers, after 21d. LPS half-reduced the cells production of calcium deposits in all groups (p < 0.05), except in the group with TDg-NPs (decrease about 10 %). SignificanceLPS induced lower mineral deposition and cytoskeletal disorganization in hDPSCs. These effects were counteracted by TDg-NPs, enhancing osteogenic differentiation and mineralization.

Immobilized Urease Vector System Based on the Dynamic Defect Regeneration Strategy for Efficient Urea Removal.

The clearance of urea poses a formidable challenge, and its excessive accumulation can cause various renal diseases. Urease demonstrates remarkable efficacy in eliminating urea, but cannot be reused. This study aimed to develop a composite vector system comprising microcrystalline cellulose (MCC) immobilized with urease and metal-organic framework (MOF) UiO-66-NH2, denoted as MCC@UiO/U, through the dynamic defect generation strategy. By utilizing competitive coordination, effective immobilization of urease into MCC@UiO was achieved for efficient urea removal. Within 2 h, the urea removal efficiency could reach up to 1500 mg/g, surpassing an 80% clearance rate. Furthermore, an 80% clearance rate can also be attained in peritoneal dialyzate from patients. MCC@UiO/U also exhibits an exceptional bioactivity even after undergoing 5 cycles of perfusion, demonstrating remarkable stability and biocompatibility. This innovative approach and methodology provide a novel avenue and a wide range of immobilized enzyme vectors for clinical urea removal and treatment of kidney diseases, presenting immense potential for future clinical applications.

Priority Intervention Evaluation of Community Regeneration in Megacities Based on the Business Improvement District (BID) Model: A Case Study of Tianjin, China

This study aims to start from the macroscale of the megacity, explore a top-down operational technical path from the identification of community regeneration units as the evaluation objects to the BID priority intervention evaluation, and then propose differentiated community regeneration strategies based on the BID model. In the post-epidemic era, it is necessary for global megacities to take new measures in urban regeneration to respond to worldwide changes and challenges. As an innovative tool to promote central city revitalization, the BID model has played an important role in community transformation. In the context of the continuous decentralization of population and industry in China’s megacities, it is urgent to explore the technical path to apply the BID model to local community regeneration. Given the shortcomings of existing studies in the method to identify the scope of BID implementation and evaluate intervention priorities, this study takes Tianjin, a megacity in China, as an example and uses DBSCAN (density-based spatial clustering of applications with noise) and service area analysis to define the community regeneration units with commercial agglomeration characteristics as the objects. Then, the BID priority intervention evaluation system is constructed from the two measurement aspects of the intervention potential and the necessity of community regeneration to classify the BID intervention priorities of community regeneration units. The main conclusions are as follows: 1. When the DBSCAN analysis parameters take the minimum number of elements as 30 and the search distance as 120 m, the result is most suitable for identifying community units with commercial agglomeration of the study area; 2. Population vitality, especially working and residential population density, is the key factor affecting BID intervention potential, while road network density is an important indicator for determining the necessity of community regeneration; 3. Community regeneration units with high BID priority levels need to develop differentiated regeneration strategies combining their BID intervention potential, regeneration necessity characteristics, and location attributes. These conclusions can provide references for the governments of megacities to screen and establish BIDs.