Clinical outcomes and risk factor analysis of dental implants inserted with lateral maxillary sinus floor augmentation: A 3- to 8-year retrospective study.

AIM: To evaluate the 3- to 8-year outcomes of dental implants placed with lateral sinus floor augmentation (LSFA) and to identify factors affecting implant survival. MATERIALS AND METHODS: This retrospective study was performed by screening all implants placed with LSFA procedures, which were conducted between January 2012 and December 2016. Subantral bone gain (SABG) and apical bone height (ABH) were assessed using panoramic radiographs. The cumulative survival rate of implants was analysed using life-table analysis and Kaplan-Meier survival curves. The influential risk factors affecting survival were assessed using univariate log-rank tests and multivariable mixture cure rate model. Implant complications were recorded. RESULTS: Based on the established criteria, a total of 449 patients (760 implants) were included in this study. In the 3- to 8-year follow-up (mean ± SD, 5.81 ± 1.33 years), 15 implants in 14 patients failed, with a CRS of 96.81% on an implant basis and 95.07% on a patient basis. A history of periodontitis and poor compliance with supportive periodontal treatment was associated with a significantly higher risk of implant failure at both implant and patient levels. Significant decreases in ABH occurred during each yearly interval except for 3 years. A similar trend has been observed for SABG at 1, 2, 6 and 8 years. The total complication rate was 31.84% on implant basis, with peri-implant mucositis (21.58%) being the most frequent biologic complication and porcelain cracking (5.00%) being the most common technical complication. CONCLUSIONS: Implant with LSFA is a reliable treatment option in atrophic maxilla. A history of periodontitis without regular supportive periodontal treatment was identified as a predictor for implant failure. Slight but significant shrinkage of vertically augmented bone can be observed after implant placement.

Clinical and radiographic outcomes of implant-supported fixed prostheses with cantilever extension in anterior mandible: A retrospective study.

OBJECTIVES: The objective of this study is to analyze the clinical and radiographic outcomes of implant-supported fixed protheses with cantilever extensions (ISFPCs) in the partially edentulous anterior mandible. MATERIALS AND METHODS: Patients who received anterior mandible implant restoration between January 2016 and December 2021 were included. Patients with two, three, or four continuous missing teeth receiving adjacent implant supported single-unit crowns (ISSCs), ISFPCs, implant-supported fixed protheses without cantilever extensions (ISFPNs) were divided into groups: ISSC+ISSC, ISFPC, ISSC+ISFPC, three-unit ISFPN, ISFPC+ISFPC, or four-unit ISFPN, respectively. We recorded and evaluated survival rates, mechanical and biological complications, peri-implant marginal bone loss (MBL), esthetic outcomes, and patient perceptions. Statistical analysis was performed using linear mixed models (LMM). RESULTS: The study included 87 patients and 152 implants. No implant loss occurred during an average follow-up of 3.48 ± 1.85 years (range: 1-7 years). According to LMM models, prosthetic type had a statistically significant impact on MBL during follow-up periods, in favor of the ISFPC and ISFPC+ISFPC groups (0.16 ± 0.48 mm vs. 0.51 ± 0.49 mm, p = .034; 0.22 ± 0.49 mm vs. 0.60 ± 0.62 mm, p = .043, respectively). Mechanical and biological complications were relatively low and comparable. The four-unit ISFPC group had higher subjective esthetic scores compared with the ISSC+ISSC group (98.6 vs. 83.8, p < .05), and patients in the ISFPC+ISFPC group expressed greater satisfaction with cleanability than the ISFPN group (98.8 vs. 80.6). CONCLUSION: ISFPCs offer a highly predictable treatment option in the anterior mandible, characterized by high survival rates, and comparable complication rates, peri-implant bone stability and esthetics to adjacent ISSCs or ISFPNs.

Soft Materials by Design: Unconventional Polymer Networks Give Extreme Properties.

Hydrogels are polymer networks infiltrated with water. Many biological hydrogels in animal bodies such as muscles, heart valves, cartilages, and tendons possess extreme mechanical properties including being extremely tough, strong, resilient, adhesive, and fatigue-resistant. These mechanical properties are also critical for hydrogels' diverse applications ranging from drug delivery, tissue engineering, medical implants, wound dressings, and contact lenses to sensors, actuators, electronic devices, optical devices, batteries, water harvesters, and soft robots. Whereas numerous hydrogels have been developed over the last few decades, a set of general principles that can rationally guide the design of hydrogels using different materials and fabrication methods for various applications remain a central need in the field of soft materials. This review is aimed at synergistically reporting: (i) general design principles for hydrogels to achieve extreme mechanical and physical properties, (ii) implementation strategies for the design principles using unconventional polymer networks, and (iii) future directions for the orthogonal design of hydrogels to achieve multiple combined mechanical, physical, chemical, and biological properties. Because these design principles and implementation strategies are based on generic polymer networks, they are also applicable to other soft materials including elastomers and organogels. Overall, the review will not only provide comprehensive and systematic guidelines on the rational design of soft materials, but also provoke interdisciplinary discussions on a fundamental question: why does nature select soft materials with unconventional polymer networks to constitute the major parts of animal bodies?

Diagnostic value of nerve conduction study in NOTCH2NLC-related neuronal intranuclear inclusion disease.

BACKGROUND AND AIMS: Neuronal intranuclear inclusion disease (NIID) is a rare progressive neurodegenerative disorder mainly caused by abnormally expanded GGC repeats within the NOTCH2NLC gene. Most patients with NIID show polyneuropathy. Here, we aim to investigate diagnostic electrophysiological markers of NIID. METHODS: In this retrospective dual-center study, we reviewed 96 patients with NOTCH2NLC-related NIID, 94 patients with genetically confirmed Charcot-Marie-Tooth (CMT) disease, and 62 control participants without history of peripheral neuropathy, who underwent nerve conduction studies between 2018 and 2022. RESULTS: Peripheral nerve symptoms were presented by 53.1% of patients with NIID, whereas 97.9% of them showed peripheral neuropathy according to electrophysiological examinations. Patients with NIID were characterized by slight demyelinating sensorimotor polyneuropathy; some patients also showed mild axonal lesions. Motor nerve conduction velocity (MCV) of the median nerve usually exceeded 35 m/s, and were found to be negatively correlated with the GGC repeat sizes. Regarding the electrophysiological differences between muscle weakness type (n = 27) and non-muscle weakness type (n = 69) of NIID, nerve conduction abnormalities were more severe in the muscle weakness type involving both demyelination and axonal impairment. Notably, specific DWI subcortical lace sign was presented in only 33.3% of muscle weakness type, thus it was difficult to differentiate them from CMT. Combining age of onset, distal motor latency, and compound muscle action potential of the median nerve showed the optimal diagnostic performance to distinguish NIID from major CMT (AUC = 0.989, sensitivity = 92.6%, specificity = 97.4%). INTERPRETATION: Peripheral polyneuropathy is common in NIID. Our study suggest that nerve conduction study is useful to discriminate NIID.

Instant tough bioadhesive with triggerable benign detachment.

Bioadhesives such as tissue adhesives, hemostatic agents, and tissue sealants have potential advantages over sutures and staples for wound closure, hemostasis, and integration of implantable devices onto wet tissues. However, existing bioadhesives display several limitations including slow adhesion formation, weak bonding, low biocompatibility, poor mechanical match with tissues, and/or lack of triggerable benign detachment. Here, we report a bioadhesive that can form instant tough adhesion on various wet dynamic tissues and can be benignly detached from the adhered tissues on demand with a biocompatible triggering solution. The adhesion of the bioadhesive relies on the removal of interfacial water from the tissue surface, followed by physical and covalent cross-linking with the tissue surface. The triggerable detachment of the bioadhesive results from the cleavage of bioadhesive's cross-links with the tissue surface by the triggering solution. After it is adhered to wet tissues, the bioadhesive becomes a tough hydrogel with mechanical compliance and stretchability comparable with those of soft tissues. We validate in vivo biocompatibility of the bioadhesive and the triggering solution in a rat model and demonstrate potential applications of the bioadhesive with triggerable benign detachment in ex vivo porcine models.

Alterations in the saliva microbiome in patients with gastritis and small bowel inflammation.

The oral microbiome is an important part of the human microbiome. Accumulating data have shown that oral microbiome alterations are closely related to multiple human diseases. However, salivary microbiota distributions remain unclear in patients with gastritis and small bowel inflammation. Magnetically guided capsule endoscopy (MGCE) is a noninvasive diagnostic tool for patients with gastritis and small bowel inflammation. Herein, we analysed the alterations in saliva microbiota in the normal, small intestinal inflammation and chronic gastritis groups through 16S rRNA gene amplicon sequencing. We found that the abundance of Lactobacillaceae was dramatically higher in chronic gastritis group than healthy individuals (p = 0.001). The levels of Porphyromonas and Faecalibaculum in gastritis samples were increased (p = 0.028; p = 0.006), and the enrichments of Faecalibaculum and Kosakonia in small intestine inflammation samples were elevated (p < 0.001; p = 0.002) compared to those in normal individuals. Our findings clarify the saliva microbiota components and their importance of specific bacteria in gastritis and small bowel inflammation.

Factors Affecting Extracellular Vesicles Based Drug Delivery Systems.

Extracellular vesicles (EVs) play major roles in intracellular communication and participate in several biological functions in both normal and pathological conditions. Surface modification of EVs via various ligands, such as proteins, peptides, or aptamers, offers great potential as a means to achieve targeted delivery of therapeutic cargo, i.e., in drug delivery systems (DDS). This review summarizes recent studies pertaining to the development of EV-based DDS and its advantages compared to conventional nano drug delivery systems (NDDS). First, we compare liposomes and exosomes in terms of their distinct benefits in DDS. Second, we analyze what to consider for achieving better isolation, yield, and characterization of EVs for DDS. Third, we summarize different methods for the modification of surface of EVs, followed by discussion about different origins of EVs and their role in developing DDS. Next, several major methods for encapsulating therapeutic cargos in EVs have been summarized. Finally, we discuss key challenges and pose important open questions which warrant further investigation to develop more effective EV-based DDS.

Natural Ingredient-Based Polymeric Nanoparticles for Cancer Treatment.

Cancer is a global health challenge. There are drawbacks to conventional chemotherapy such as poor bioavailability, development of drug resistance and severe side effects. Novel drug delivery system may be an alternative to optimize therapeutic effects. When such systems consist of natural materials, they offer important advantages: they are usually highly biocompatible, biodegradable, nontoxic and nonimmunogenic. Furthermore, natural materials can be easily modified for conjugation with a wide range of therapeutic agents and targeting ligands, according to the therapeutic purpose. This article reviews different natural ingredients and their applications in drug delivery systems for cancer therapy. Firstly, an overview of the polysaccharides and protein-based polymers that have been extensively investigated for drug delivery are described. Secondly, recent advances in using various natural ingredient-based polymeric nanoparticles for cancer therapy are reviewed. The characteristics of these delivery systems are summarized, followed by a discussion of future development and clinical potential. This review aims to summarize current knowledge and provide a basis for developing effective tailor-made formulations for cancer therapy in the future.

Bioadhesive Polymersome for Localized and Sustained Drug Delivery at Pathological Sites with Harsh Enzymatic and Fluidic Environment via Supramolecular Host-Guest Complexation.

Targeted and sustained delivery of drugs to diseased tissues/organs, where body fluid exchange and catabolic activity are substantial, is challenging due to the fast cleansing and degradation of the drugs by these harsh environmental factors. Herein, a multifunctional and bioadhesive polycaprolactone-ß-cyclodextrin (PCL-CD) polymersome is developed for localized and sustained co-delivery of hydrophilic and hydrophobic drug molecules. This PCL-CD polymersome affords multivalent crosslinking action via surface CD-mediated host-guest interactions to generate a supramolecular hydrogel that exhibits evident shear thinning and efficient self-healing behavior. The co-delivery of small molecule and proteinaceous agents by the encapsulated PCL-CD polymersomes enhances the differentiation of stem cells seeded in the hydrogel. Furthermore, the PCL-CD polymersomes are capable of in situ grafting to biological tissues via host-guest complexation between surface CD and native guest groups in the tissue matrix both in vitro and in vivo, thereby effectively extending the retention of loaded cargo in the grafted tissue. It is further demonstrated that the co-delivery of small molecule and proteinaceous drugs via PCL-CD polymersomes averts cartilage degeneration in animal osteoarthritic (OA) knee joints, which are known for their biochemically harsh and fluidically dynamic environment.

Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review.

Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed.

Sulfated Chitosan-Modified CuS Nanocluster: A Versatile Nanoformulation for Simultaneous Antibacterial and Bone Regenerative Therapy in Periodontitis.

Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu2+-induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum, thereby suppressing bacteria growth and biofilm formation in vitro, but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.

Mesenchymal stem cells and dental implant osseointegration during aging: from mechanisms to therapy.

Dental implants are widely used to replace missing teeth, providing patients with unparalleled levels of effectiveness, convenience, and affordability. The biological basis for the clinical success of dental implants is osseointegration. Bone aging is a high-risk factor for the reduced osseointegration and survival rates of dental implants. In aged individuals, mesenchymal stem cells (MSCs) in the bone marrow show imbalanced differentiation with a reduction in osteogenesis and an increase in adipogenesis. This leads to impaired osseointegration and implant failure. This review focuses on the molecular mechanisms underlying the dysfunctional differentiation of aged MSCs, which primarily include autophagy, transcription factors, extracellular vesicle secretion, signaling pathways, epigenetic modifications, microRNAs, and oxidative stress. Furthermore, this review addresses the pathological changes in MSCs that affect osseointegration and discusses potential therapeutic interventions to enhance osseointegration by manipulating the mechanisms underlying MSC aging.

Atomistic picture of isothermal volume relaxation behavior of atactic polystyrene glass provided by a molecular dynamics simulation.

Using an atomistic molecular dynamics (MD) simulation, we study the volume relaxation behavior of atactic polystyrene and attempt to correlate this macroscopic behavior with certain microscopic aspects. To this end, the gyration radius, the dimensionless relative shape anisotropy, the mean-squared displacement, and the non-Gaussian parameter are examined simultaneously. Our result shows that the structures characterized at different length scales change in a self-similar way and these changes are intimately correlated to the translational mobility of atoms. The initial incubation of structural changes at the different scales originates from the restriction of mobility due to the cage effect. The applicability of the MD simulation to the investigation of the bulk properties is discussed.

PEGylated Prussian blue nanoparticles for modulating polyethyleneimine cytotoxicity and attenuating tumor hypoxia for dual-enhanced photodynamic therapy.

Photodynamic therapy (PDT) is a promising cancer therapy modality due to its intrinsically negligible side effects and treatment resistance. However, the development of the high-efficiency PDT still remains a challenge. Herein, a nanodrug platform PEG-Ce6-PEI@PB combined tumor acidity-induced polyethyleneimine (PEI) cytotoxicity with an oxygen self-supply property is developed for dual-enhanced PDT. The obtained PEG-Ce6-PEI@PB presents suppressed PEI cytotoxicity and chlorin e6 (Ce6) phototoxicity during the bloodstream before becoming active in tumor tissues/cells. The acidic tumor microenvironment can shed PEG coating to rebound PEI positive charges, facilitating tumor cell uptake and reverting the PEI cytotoxicity to enhance following PDT. Moreover, Prussian blue (PB) nanozymes with catalase-like activity can convert endogenous hydrogen peroxide into oxygen to relieve tumor hypoxia, which is attributed to the photosensitizer Ce6 producing more cytotoxic reactive oxygen species upon laser irradiation to further strengthen PDT. Moreover, PEG-Ce6-PEI@PB exhibits good biocompatibility and long blood circulation. More importantly, PEG-Ce6-PEI@PB-treated breast cancer cells and tumor-bearing mice present effective therapeutic efficacy upon laser irradiation, verifying the synergistic antitumor effects of PEI cytotoxicity and oxygen self-supplying PDT.

Exploring the influence mechanisms of polystyrene-microplastics on sewage sludge composting.

To explore the influence mechanisms of polystyrene-microplastics (PS-MPs) on sewage sludge composting and put forward relevant composting adjustment strategies, a 30-day sewage sludge (SS) composting experiment was conducted by adding 0%, 0.5%, and 1% (w/w) PS-MPs. The addition of PS-MPs reduced compost temperature, microbial biomass carbon (MBC), and the degradation of volatile solids (2.6%-4.8%), and inhibited the activities of key enzymes (ß-glucosidase and alkaline phosphatase) but increased urease activity in the thermophilic phase. Moreover, PS-MPs altered the relative abundance of dominant bacteria and changed the relevance of main enzymes and bacterial communities. Moreover, high levels of PS-MPs inhibited the contribution of dominant bacterial to alkaline phosphatase and ß-glucosidase. Redundancy analysis revealed that PS-MPs affected the composting process mainly through reduced MBC at the mesophilic phase and temperature at the thermophilic phase. Thus, regulating MBC and temperature in specific phases could help overcome the adverse effects of PS-MPs on composting.

Bioadhesive ultrasound for long-term continuous imaging of diverse organs.

Continuous imaging of internal organs over days could provide crucial information about health and diseases and enable insights into developmental biology. We report a bioadhesive ultrasound (BAUS) device that consists of a thin and rigid ultrasound probe robustly adhered to the skin via a couplant made of a soft, tough, antidehydrating, and bioadhesive hydrogel-elastomer hybrid. The BAUS device provides 48 hours of continuous imaging of diverse internal organs, including blood vessels, muscle, heart, gastrointestinal tract, diaphragm, and lung. The BAUS device could enable diagnostic and monitoring tools for various diseases.

Coassembled Nitric Oxide-Releasing Nanoparticles with Potent Antimicrobial Efficacy against Methicillin-Resistant Staphylococcus aureus (MRSA) Strains.

Nitric oxide (NO)-releasing nanoparticles are effective nanomedicines with diverse therapeutic advantages compared with small molecule-based NO donors. Here, we report a new class of furoxan-based NO-releasing nanoparticles using a simple, creative yet facile coassembly approach. This is the first time we demonstrated that the coassembled NO-releasing nanoparticles with poly(ethylene glycol)101-block-poly(propylene glycol)56-block-poly(ethylene glycol)101 (Pluronic F127) had potent antimicrobial efficacies against methicillin-resistant Staphylococcus aureus (MRSA) strains. Nanoparticles obtained from the coassembly of either 4-(1-(3-methylpentan-5-ol)oxyl)(3-phenylsulfonyl) furoxan (compound 1) or 4-methoxy(3-phenylsulfonyl) furoxan (compound 2) with Pluronic F127 exhibit 4-fold improved antimicrobial activities compared to their self-assembled counterparts without Pluronic F127. 5(6)-Carboxylfluorescein (CF) leakage experiments further reveal that both coassembled NO-releasing nanoparticles show stronger interactions with lipid bilayers than those self-assembled alone. Subsequently, their strong plasma membrane-damaging capabilities are confirmed under both high-resolution optical microscopy and scanning electron microscopy characterizations. This coassembly approach could be readily applied to other small molecule-based antimicrobials, providing new solutions and important insights to further antimicrobial recipe design.

Effectiveness of telerehabilitation on short-term quality of life of patients after esophageal cancer surgery during COVID-19: a single-center, randomized, controlled study.

BACKGROUND: The occurrence of postoperative complications may lead to delayed recovery and a decline in physical function in the first 3 months after esophagectomy. The outbreak of COVID-19 imposed physical and emotional obstacles for traditional face-to-face rehabilitation. Meanwhile, the effectiveness of telerehabilitation remained unknown. In this study, we aimed to investigate the effectiveness of telerehabilitation. METHODS: A cohort of 86 patients who received minimally invasive esophagectomy between September 2020 and January 2021 was randomly allocated into two groups. The telerehabilitation group received additional online consulting and training, including (I) precautions for nutritional support; (II) swallowing function training; (III) respiratory function training; (IV) guidance and feedback on matters such as patient's current vital signs, wound status, medication, and sleep status. The primary outcome was the change of quality of life (QOL) of each patient at 3 months after surgery. RESULTS: No serious adverse events were observed in either group. The telerehabilitation group showed significant improvements in pain using the OLQ-C30 scale (P<0.001), and in choking using the QLQ-OES18 scale (P<0.001). The comparison of the QLQ-C30 and QES-18 score changes at three months after discharge revealed that nearly all aspects in the telerehabilitation group displayed more score changes with significant changes in the appetite loss and pain part (P<0.001 and P<0.05, respectively). The score changes in QLQ-OES18 revealed significant improvement in swallowing saliva (P<0.05), as well slight improvements in choking, dry mouth, taste, and cough without significance. CONCLUSIONS: Our study demonstrated that telerehabilitation was at least an important supplement to traditional face-to-face consulting and training for patients after esophageal cancer surgery during the COVID-19 period. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100049186.

An Innovative Solvent-Responsive Coiling-Expanding Stent.

Coronary artery disease is the "first killer" in the world, while the classical treatment for this disease is to implant stent. An ideal vascular stent should be nontoxic with self-expanding characteristics, quick expanding speed, and appropriate mechanical supporting property. However, no existing vascular stent covers all properties. Herein, a two-way shape-memory cellulose vascular stent, which can realize shape adjustments by mild solutions such as water and alcohol, is constructed. The shape-memory characteristics, mechanical properties, cell toxicity, and biocompatibility, are systemically investigated by ex vivo experiment as well as molecule simulation and theoretical modeling, revealing that the achieved bilayer two-way shape-memory films (BSMFs) can be used as an artificial vascular stent. In particular, this vascular stent made from BSMFs shows superb biocompatibility according to live/dead cell viability assays. Ex vivo experiments reveal that the novel vascular stent can support arteria coronaria sinistra, or the left main coronary artery, at the opening state while the cross-section of the vessel becomes two times larger than that of the initial state after implantation. Thus, it is believed that effective and scalable BSMFs can make meritorious fundamental contributions to biomaterials science and practical applications such as vascular stents.

Enhanced mechanosensing of cells in synthetic 3D matrix with controlled biophysical dynamics.

3D culture of cells in designer biomaterial matrices provides a biomimetic cellular microenvironment and can yield critical insights into cellular behaviours not available from conventional 2D cultures. Hydrogels with dynamic properties, achieved by incorporating either degradable structural components or reversible dynamic crosslinks, enable efficient cell adaptation of the matrix and support associated cellular functions. Herein we demonstrate that given similar equilibrium binding constants, hydrogels containing dynamic crosslinks with a large dissociation rate constant enable cell force-induced network reorganization, which results in rapid stellate spreading, assembly, mechanosensing, and differentiation of encapsulated stem cells when compared to similar hydrogels containing dynamic crosslinks with a low dissociation rate constant. Furthermore, the static and precise conjugation of cell adhesive ligands to the hydrogel subnetwork connected by such fast-dissociating crosslinks is also required for ultra-rapid stellate spreading (within 18 h post-encapsulation) and enhanced mechanosensing of stem cells in 3D. This work reveals the correlation between microscopic cell behaviours and the molecular level binding kinetics in hydrogel networks. Our findings provide valuable guidance to the design and evaluation of supramolecular biomaterials with cell-adaptable properties for studying cells in 3D cultures.