Gelation Kinetics Research Articles

Looping and gelation kinetics in reversible networks based on furan and maleimide

This work presents a detailed kinetic study on the Diels-alder reaction between furan and maleimide moieties based on variable temperature infrared spectroscopy. BMI–689 was mixed with a multifunctional furan monomer. The furan functionality of the furan-bearing monomers was varied to observe any differences in reaction conversion and the resulting kinetic description of these networks. The endo and exo stereo isomers being formed during the Diels-Alder reaction are considered in this description and have been observed through ex-situ 1H–NMR spectroscopy. The kinetic parameters were further used to predict the required percolation time for each system at any temperature. The activation energy of the forward Diels-Alder reactions were between 46 and 60 kJ mol-1 and backward activation energies between 87 and 119 kJ mol-1. Only minor differences were found in the final Diels-Alder conversion developments by comparing systems with a varying monomer functionality, implying that the percolation process does not influence the kinetics for these systems. Finally, we shed light on the percolation process and occurrence of looping throughout the reaction of the used bismaleimide and various furan-bearing constituents via coarse-grained molecular dynamics simulations. The results of this study form a basis for understanding the temperature dependent self-healing behavior of such materials, and for defining temperature programs in 3D printing and extrusion applications, where rapid solidification while ensuring reprocessability are the main challenges.

Effects of Moisture Content and Heat Treatment on the Viscoelasticity and Gelation of Polyacrylonitrile/Dimethylsulfoxide Solutions

Polyacrylonitrile (PAN) gels create significant obstacles in industrial fiber spinning by forming insoluble networks that compromise solution stability and uniformity. This study investigates the rheological properties of PAN/dimethyl sulfoxide (DMSO) solutions, examining how aging time, moisture content, and polymer concentration affect gelation behavior. Dynamic rheological analysis revealed that both physical and chemical crosslinks play crucial roles in gel formation, with gelation accelerating markedly when moisture content exceeds 3% and aging progresses. Under heat treatment at 80 °C, samples with increased moisture content demonstrated rapid transitions to solid-like states, indicating a critical moisture threshold for enhanced gelation kinetics. Additionally, reductions in polymer concentration disrupted physical crosslink density, thereby mitigating gel formation. These results underscore the importance of precisely controlling moisture and concentration parameters in PAN solutions to stabilize solution properties and minimize gel formation, thus enhancing process efficiency and quality in PAN-based carbon fiber production.

Controlling the co-aggregation and gelation of cod-soy binary proteins based on partially/fully denatured soy proteins

Structured binary protein networks offer a pathway for designing gel-based foods with less ecological and economic effects. This study investigated the heat-mediated interaction and gelation kinetics of cod-soy mixed proteins at molecular level. Results indicated that denaturation degree of soy proteins was fundamental in determining the protein-protein interactions during heating. Considerable non-natural β-sheet was generated in the heterogeneous structures to initiate their aggregation behavior. Cod actomyosin comprising myosin heavy chains and actin mainly regulated their aggregation below 70 °C. At higher temperatures, the formation of large-sized and intermediary-sized aggregates was dominated by disulfide bond exchange between cod actomyosin and soy A-B aggregates (≤ 85 °C) or dissociated B subunits (> 85 °C). These aggregates were further evidenced as essential components to form gel networks with higher storage modulus (G'). These findings provide fundamental insights for designing gel-based products with desirable nutritional and textural properties based on plant-animal binary proteins.

Investigating the pH-Dependence of Gelation process in Chitosan-glutaraldehyde Hydrogels with Diffusing Wave Spectroscopy

The gel time of functional hydrogels is an essential property that dictates their utility in various applications. To accurately assess this parameter, the chitosan-glutaraldehyde hydrogels were characterized here using two complementary analytical tools, rotational rheometer, and diffusing wave spectrometer (DWS). Rotational rheometers are widely used to continuously monitor the macro-mechanical properties of hydrogels during the gelation process. By observing the modulus change curve, one can gain insights into the instantaneous changes occurring within the gel network. This method provides a direct measurement of the gel's mechanical strength; however, it involves applying external forces to the sample, which may introduce artifacts such as measurement lag and potential sample deformation or destruction. Results of this study indicated that the application of external force during rotary rheometer measurements disrupted the gelation process. In contrast, DWS detected alterations in the microstructure by measuring light diffusion, allowing to track microstructural changes post-crosslinking, and curing without the interference of external stress. Thus, DWS offers a non-invasive approach to studying gelation as it detected the Brownian motion of particles within the hydrogel by monitoring the diffraction of light, thereby providing undisturbed dynamic information about the gel's behavior. The DWS technique is particularly useful for tracking microstructural changes that occur during hydrogel crosslinking and curing, without altering the gel's native state. An additional advantage of DWS is its ability to investigate the pH effect on gelation. By measuring changes in gelation time as a function of pH, we could achieve precise control over the gelation process. This fine-tuning of gelation kinetics is crucial for applications that require rapid or delayed gelation, offering a level of precision that is difficult to match with traditional rheological methods.

Process Mapping of the Sol-Gel Transition in Acid-Initiated Sodium Silicate Solutions.

Fabricating large-scale porous bioactive glass bone scaffolds presents significant challenges. This study aims to develop formable, in situ setting scaffolds with a practical gelation time of about 10 min by mixing 45S5 bioactive glass with sodium silicate (waterglass) and an acid initiator. The effects of pH (2-11), waterglass concentration (15-50 wt.%), and acid initiator type (phosphoric or boric acid) were examined to optimize gelation kinetics and microstructure. A 10 min gelation time was achieved with boric acid and phosphoric acid at various pH levels by adjusting the waterglass concentration. Exponential and polynomial models were proposed to predict gelation times in basic and acidic environments, respectively. The optical properties of the gels were studied qualitatively and quantitatively, providing insights into gelation kinetics and structure. Acidic gels formed smaller particles in a dense network (pores < 550 nm) with higher light transmittance, while basic gels had larger aggregates (pores ~5 µm) and lower transmittance. As the waterglass concentration decreased, pore size and transmittance converged in both groups. The onset of gelation was detected around 8 min using the derivative of light transmittance. This work identifies the key factors controlling waterglass gelation and their impact on gel structure, enabling the tailored creation of formable, in situ setting bioactive glass bone scaffolds.

Exosomes from hypoxic urine-derived stem cells facilitate healing of diabetic wound by targeting SERPINE1 through miR-486-5p

Vascular pathologies and injuries are important factors for the delayed wound healing in diabetes. Previous studies have demonstrated that hypoxic environments could induce formation of new blood vessels by regulating intercellular communication and cellular behaviors. In this study, we have enhanced the angiogenic potential of exosomes by subjecting urine-derived stem cells (USCs) to hypoxic preconditioning. To prolong the retention of exosomes at the wound site, we have also engineered a novel dECM hydrogel termed SISMA, which was modified from porcine small intestinal submucosa (SIS). For its rapid and controllable gelation kinetics, excellent biocompatibility, and exosome release capability, the SISMA hydrogel has proven to be a reliable delivery vehicle for exosomes. The hypoxia-induced exosomes-loaded hydrogel has promoted endothelial cell proliferation, migration, and tube formation. More importantly, as evidenced by significant in vivo vascular regeneration in the early stages post-injury, it has facilitated tissue repair. This may because miR-486–5p in H-exo inhibit SERPINE1 activity in endothelial cell. Additionally, miRNA sequencing analysis suggested that the underlying mechanism for enhanced angiogenesis may be associated with the activation of classical HIF-1α signaling pathway. In summary, our study has presented a novel non-invasive, cell-free therapeutic approach for accelerating diabetes wound healing and development of a practical and efficient exosomes delivery platform.

Magnesium Nanocomposite Hydrogel Reverses the Pathologies to Enhance Mandible Regeneration.

The healing of bone defects after debridement in medication-related osteonecrosis of the jaw (MRONJ) is a challenging medical condition with impaired angiogenesis, susceptible infection, and pro-inflammatory responses. Magnesium (Mg) nanocomposite hydrogel is developed to specifically tackle multiple factors involved in MRONJ. Mg-oxide nanoparticles tune the gelation kinetics in the reaction between N-hydroxysuccinimide-functionalized hyperbranched poly (ethylene glycol) and proteins. This reaction allows an enhanced mechanical property after instant solidification and, more importantly, also stable gelation in challenging environments such as wet and hemorrhagic conditions. The synthesized hydrogel guides mandible regeneration in MRONJ rats by triggering the formation of type H vessels, activating Osterix+ osteoprogenitor cells, and generating anti-inflammatory microenvironments. Additionally, this approach demonstrates its ability to suppress infection by inhibiting specific pathogens while strengthening stress tolerance in the affected alveolar bone. Furthermore, the enhanced osteogenic properties and feasibility of implantation of the hydrogel are validated in mandible defect and iliac crest defect created in minipigs, respectively. Collectively, this study offers an injectable and innovative bone substitute to enhance mandible defect healing by tackling multiple detrimental pathologies.

Re-entrant phase transitions in Laponite/Gum Arabic nanocomposites

A re-entrant gel transition is observed in a discotic clay, Laponite (Lap) aqueous suspensions with the addition of a complex polysaccharide, Gum Arabic (GA). For fixed concentrations of Lap (1–3 % w/v) and at low GA concentrations (CGA < 10 % w/v), the composites exhibit gel behaviour, while the suspensions undergo liquid phase separation for intermediate GA concentrations (10 % w/v < CGA < 20 % w/v). Gel behaviour is again observed in the samples at even higher GA concentrations (CGA > 30 % w/v). Here, we identify a thermodynamic phase transition in Lap/GA mixtures that is caused by a variation in GA content. The viscoelastic characteristics, phase transitions, and gelation kinetics of the Lap/GA mixtures have been studied by employing rheology, small-angle X-ray scattering, and optical investigations. Reduction of the negative values of zeta-potential and growth of the composite system's hydrodynamic size indicated the presence of interactions in Lap/GA mixtures. The phase diagram enables the apparent interactions and phase transitions between the nanoplatelets and the complex polysaccharides. Thus, our study provides new perspectives on a nanocomposite's tuneable rheological and structural features.

Exosome Loaded Protein Hydrogel for Enhanced Gelation Kinetics and Wound Healing.

Exosomes are being increasingly explored in biomedical research for wound healing applications. Exosomes can improve blood circulation and endocrine signaling, resulting in enhanced cell regeneration. However, exosome treatments suffer from low retention and bioavailability of exosomes at the wound site. Hydrogels are a popular tool for drug delivery due to their ability to encapsulate drugs in their network and allow for targeted release. Recently, hydrogels have proven to be an effective method to provide increased rates of wound healing when combined with exosomes that can be applied noninvasively. We have designed a series of single-domain protein-based hydrogels capable of physical cross-linking and upper critical solution temperature (UCST) behavior. Hydrogel variant Q5, previously designed with improved UCST behavior and a significantly enhanced gelation rate, is selected as a candidate for encapsulation release of exosomes dubbed Q5Exo. Q5Exo exhibits low critical gelation times and significant decreases in wound healing times in a diabetic mouse wound model showing promise as an exosome-based drug delivery tool and for future hybrid, noninvasive protein-exosome design.

Mesoscopic structure modeling of silica aerogels using cluster‐cluster aggregation

AbstractSilica aerogels are nanostructured materials known for their low density, high porosity, and excellent thermal insulation properties. Among silica aerogels, organosilane‐derived aerogels have received considerable interest for their additional chemical functionalities such as hydrophobicity and flexibility. This work investigates the mesoscopic modeling of such aerogels, extending an aggregation based model developed for conventional silica aerogels. The pH of sol–gel polymerizations is one of the most critical reaction and processing parameters in determining the porosity, density, strength, and transparency of the resulting gels. Achieving optical transparency in aerogels depends on the presence of homogeneous mesoporous network structures. To account for the effect of pH, a relationship between pH and adhesion probability was incorporated into a three‐dimensional cluster‐cluster aggregation (CCA) model, providing insight into the gelation process. In addition, size‐dependent diffusivities are considered in this study. By incorporating different factors into the CCA model, the gelation kinetics are evaluated. The obtained mesoscopic structure is compared with experimental characterizations, together with preliminary mechanical simulations.

Could Olympic Gels of Polystyrene be Produced by ARGET ATRP From Bifunctional Initiators?

The kinetics of gelation in the Activators Regenerated by Electron Transfer Atom Transfer Radical Polymerization (ARGET ATRP) of styrene, using a bifunctional initiator and no crosslinking agents are investigated. By applying the method of moments, we develop a system of differential equations that accounts for the formation of polymer rings. The kinetic rate constants of this model are optimized on the experimentally determined kinetics, varying the reaction temperature and ethanol fraction. Subsequently, we explore how variations in the amounts of catalyst, initiator, and reducing agents affect the simulated equilibria of ARGET ATRP, the emergence of gelation, and the swelling properties of the resulting networks. These findings suggest that favoring ring formation enhances the gelation phenomenon, supporting the hypothesis that the networks formed under the reported reaction conditions are olympic gels.

Generation of a pancreas derived hydrogel for the culture of hiPSC derived pancreatic endocrine cells

Stem cell-derived β-cells (SC-BCs) represent a potential source for curing diabetes. To date, in vitro generated SC-BCs display an immature phenotype and lack important features in comparison to their bona-fide counterparts. Transplantation into a living animal promotes SC-BCs maturation, indicating that components of the in vivo microenvironment trigger final SC-BCs development. Here, we investigated whether cues of the pancreas specific extracellular matrix (ECM) can improve the differentiation of human induced pluripotent stem cells (hiPSCs) towards β-cells in vitro. To this aim, a pancreas specific ECM (PanMa) hydrogel was generated from decellularized porcine pancreas and its effect on the differentiation of hiPSC-derived pancreatic hormone expressing cells (HECs) was tested. The hydrogel solidified upon neutralization at 37 °C with gelation kinetics similar to Matrigel. Cytocompatibility of the PanMa hydrogel was demonstrated for a culture duration of 21 days. Encapsulation and culture of HECs in the PanMa hydrogel over 7 days resulted in a stable gene and protein expression of most β-cell markers, but did not improve β-cell identity. In conclusion, the study describes the production of a PanMa hydrogel, which provides the basis for the development of ECM hydrogels that are more adapted to the demands of SC-BCs.

Operando monitoring of gelation kinetics of polyacrylamide hydrogel using in-fiber dual-MZI

Operando monitoring of gelation kinetics and exploring the gelation law are crucial for optimizing the performance of hydrogels. In this paper, we propose a novel superposition sensing structure based on an integrated dual-Mach–Zehnder interferometer (MZI), which can simultaneously sense temperature and refractive index (RI), with an RI sensitivity of −10,173 nm/RIU and a temperature sensitivity of 8.14 nm/ °C. For the first time, its application for the operando monitoring of gelation kinetics of polyacrylamide hydrogel (PAH) is demonstrated. By establishing the kinetic curves of temperature and RI information in the gelation process, it is confirmed that the gelation process can be divided into three stages: initial lag, rapid gelation, and final saturation. In addition, two gelation laws are verified through experiments: (1) As the concentration of monomers and crosslinkers increases, RI changes, and the amount of heat released gradually increases. (2) As the concentration of catalysts increases, the gelation time decreases significantly. This superposition sensing technique based on dual-MZI can be further applied to monitor other complex dynamic biochemical processes, thereby providing insights into the laws and mechanisms of reaction processes.

Oral viscous budesonide solution for enhanced localized treatment of eosinophilic esophagitis through improved mucoadhesion and permeation

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that is immune/antigen-mediated and often requires targeted treatment. In clinical practice, an oral viscous budesonide suspension prepared by adding sucralose to a budesonide suspension for inhalation (Pulmicort®) is used to treat adult EoE and enhance retention in the esophageal mucosa. Inspired by this off-label drug use, oral viscous budesonide solutions (OVBSs) were developed in this study, and their capacities for adhesion, permeation, and stability were explored. Given the insolubility of budesonide as a BCS II drug, we first evaluated its equilibrium solubility and found that Transcutol® HP was an excellent choice for creating an OVBS at a concentration of 0.2 mg/g. The rheological properties of the OVBSs were evaluated with a rheometer, and shear-thinning, which aids in swallowing, was observed. The addition of hydroxyethyl cellulose (HEC) increased the adhesion strength of the preparation, which was associated with the hydration and thickening mechanism. This result was confirmed in a dynamic gelation study and in vitro elution experiment conducted with porcine esophagus tissue. Furthermore, the permeabilities of the OVBSs in the porcine esophagus were evaluated with a Franz diffusion cell device. >80 % of the budesonide was released after 24 h, and the release profile was similar to that of the solution. To explore the storage conditions of OVBSs, critical factors such as pH, content, and impurities were determined. It was found that OVBSs exhibited different behaviors at different pH values and temperatures. Notably, the OVBSs containing 1.7 % HEC could be stored for >6 months at a temperature of 5 °C ± 3 °C and a pH of 4.5 without significant degradation. Overall, this study demonstrated that OVBSs have the potential to adhere to the esophageal mucosa, permeate the tissue, and remain stable during storage. Moreover, OVBSs exhibit a distinct advantage over traditional converted inhalation-to-oral budesonide therapies by enabling flexible dose adjustment in clinical applications, thereby potentially minimizing systemic side effects commonly associated with oral glucocorticoid administration.

Silk acid-tyramine hydrogels with rapid gelation properties for 3D cell culture

Silk fibroin (SF) can be enzymatically crosslinked through tyrosine residues to fabricate hydrogels with good biocompatibility and tunable mechanical properties. Using tyramine substitution can increase the phenolic group content to facilitate the gelation kinetics and mechanical properties. In this study, a two-step chemical modification method is demonstrated to synthesize silk acid-tyramine (SA-TA) conjugates with a high phenolic group content (>7 mol%). The SA-TA shows rapid enzyme-catalyzed gelation property where the sol–gel transition takes less than 10 s at 37 °C, allowing cell encapsulation with uniform distribution while maintaining high cell viability (>90 %). Furthermore, the enzyme-catalyzed SA-TA hydrogels show enhanced storage modulus than enzyme-catalyzed SF hydrogels, long-term stability, and good cytocompatibility, indicating their great potential in 3D cell culture. The in vivo implantation study demonstrates that the SA-TA hydrogels are biodegradable with a mild immune response. This implies that SA-TA hydrogels can be applied in various medical applications, such as tissue engineering, cell delivery, and 3D bioprinting. Statement of significanceIn this study, a two-step chemical modification method is demonstrated to synthesize silk acid-tyramine (SA-TA) conjugates with a high phenolic group content (>7 mol%). Owing to the increased content of the phenolic group, the SA-TA shows rapid enzyme-catalyzed gelation property where the sol–gel transition takes less than 10 s at 37 °C, allowing cell encapsulation with uniform distribution while maintaining high cell viability (>90 %). Furthermore, the enzyme-catalyzed SA-TA hydrogels show enhanced storage modulus than enzyme-catalyzed SF hydrogels, long-term stability, and good cytocompatibility, indicating their great potential in 3D cell culture. The in vivo implantation study demonstrates that the SA-TA hydrogels are biodegradable with a mild immune response. This implies that SA-TA hydrogels can be applied in various medical applications, such as tissue engineering, cell delivery, and 3D bioprinting.

Temperature effects on ribbon characteristics in soft gelatin capsule manufacture

In the manufacture of soft gelatin capsules using a rotary-die encapsulation machine, the formation of ribbons at the cooling drums and their subsequent mechanical performance are key attributes for a smooth machinability. In this paper we present the results of a comprehensive investigation of the intricate impact of the cooling drum temperature in the range between 5 and 25 °C on the mechanical and the microstructural properties of a highly concentrated gelatin formulation (40% w/w) typically used in soft capsule manufacture.The study demonstrates that the temperature at the cooling drums strongly affects the gelation kinetics, the gel elasticity and the tensile strength of the ribbons. The temperature correlates linearly with the storage modulus G′ under low shear deformation, i.e. the lower the temperature of the gel, the higher the gel elasticity. A reverse linear relationship was found for the temperature-dependent ultimate tensile strength (UTS) of the gelatin ribbons, i.e. a higher drum temperature leads to a higher UTS. This inverse effect of the ageing temperature on G′ and UTS can be explained by temperature-induced microstructural differences within the gel network, as indicated by FTIR spectroscopy and Differential Scanning Calorimetry (DSC) measurements. Lower ageing temperatures result in a higher number of triple helical junction zones with fewer and/or weaker hydrogen bonds, which translate into a higher gel elasticity under low shear deformation, but a lower resilience of the ribbons against rupture in tensile testing. At higher temperatures, fewer but longer and/or more thermostable triple helical links in the gel network enhance the stability of the ribbons against tensile stress.In summary, the results clearly reveal that a detailed understanding of the complex relationship between the drum temperature, the gel network structure and the mechanical properties of gelatin ribbons is essential for process optimization.

Well-Defined Synthetic Copolymers with Pendant Aldehydes Form Biocompatible Strain-Stiffening Hydrogels and Enable Competitive Ligand Displacement.

Dynamic hydrogels are attractive platforms for tissue engineering and regenerative medicine due to their ability to mimic key extracellular matrix (ECM) mechanical properties like strain-stiffening and stress relaxation while enabling enhanced processing characteristics like injectability, 3D printing, and self-healing. Systems based on imine-type dynamic covalent chemistry (DCvC) have become increasingly popular. However, most reported polymers comprising aldehyde groups are based on either end-group-modified synthetic or side-chain-modified natural polymers; synthetic versions of side-chain-modified polymers are noticeably absent. To facilitate access to new classes of dynamic hydrogels, we report the straightforward synthesis of a water-soluble copolymer with a tunable fraction of pendant aldehyde groups (12-64%) using controlled radical polymerization and their formation into hydrogel biomaterials with dynamic cross-links. We found the polymer synthesis to be well-controlled with the determined reactivity ratios consistent with a blocky gradient microarchitecture. Subsequently, we observed fast gelation kinetics with imine-type cross-linking. We were able to vary hydrogel stiffness from ≈2 to 20 kPa, tune the onset of strain-stiffening toward a biologically relevant regime (σc ≈ 10 Pa), and demonstrate cytocompatibility using human dermal fibroblasts. Moreover, to begin to mimic the dynamic biochemical nature of the native ECM, we highlight the potential for temporal modulation of ligands in our system to demonstrate ligand displacement along the copolymer backbone via competitive binding. The combination of highly tunable composition, stiffness, and strain-stiffening, in conjunction with spatiotemporal control of functionality, positions these cytocompatible copolymers as a powerful platform for the rational design of next-generation synthetic biomaterials.

Impact assessment of polymer, cross-linker, and nanoparticles on gelation kinetics and properties of silica nanocomposite hydrogel for water shut-off treatment in harsh reservoir conditions

The study presented the impacts of various parameters like compositional combinations of PHPA (partially hydrolyzed polyacrylamide), organic cross-linker (hydroquinone-HQ and hexamethylenetetramine-HX), and silica nanoparticles (SNP) in addition to the degree of hydrolysis and molecular weight of PHPA on the efficacy of hydrogel for water shut-off jobs. The investigation indicated that the gelation time, gel strength of the gel, tolerance against salinity, and temperature were tuned as required by the field conditions by changing the variables mentioned above. The gelation time was found to vary inversely with the concentration of polymer, cross-linkers, and silica nanoparticles, whereas the gel strength and temperature tolerance followed the reverse trend. SNP was observed to control the gel properties significantly, even at the lower polymer and cross-linker compositions, as evidenced by the stronger network in FESEM, rheological, and other related properties. The hydrogels prepared with the PHPA-LM (low molecular wt) and PHPA-HM (high molecular wt) polymers and HX-HQ cross-linkers showed improved temperature tolerance from 126.49 °C to 131.78 °C and 99.88 °C to 164.34 °C, respectively when improvised with SNP. The gel’s microstructure (FE-SEM image) exhibited significant silica nanoparticle aggregation and evenly distributed compact three-dimensional network structure. The prepared nanohydrogel with optimized composition maintained its stability even at a salinity of 60000 ppm and 120 °C for more than two years. Sand-pack flooding with the nanohydrogel proved very effective, with a permeability reduction of ∼ 90 %. Thus, the prepared nano-hydrogel could be effectively used for high temperature and high salinity conditions with preferred resistance to water flow.

Assessing rheological properties of oxidized Moringa oleifera gum and carboxymethyl chitosan‐based self‐healing hydrogel for additive manufacturing applications

AbstractRheology plays a vital role in pneumatic three‐dimensional (3D) printing of hydrogels. This study investigates the rheological behavior of a novel self‐healing hydrogel (O‐MOG/CMCh) formed by a Schiff base crosslinking reaction between oxidized Moringa oleifera gum (O‐MOG), a biodegradable antimicrobial polysaccharide, and carboxymethyl chitosan (CMCh), a water‐soluble biocompatible chitosan derivative. Three hydrogel formulations were designed using 5% w/v of CMCh with varied concentrations of O‐MOG (3% w/v, 4% w/v, and 5% w/v) and evaluated through rheology analyses, including frequency sweeps, amplitude sweeps, oscillatory thixotropy, and gelation kinetics. These tests revealed that the material has shear thinning, self‐healing properties, a high linear viscoelastic region (LVE), and gel formation times (tgel) of 3.23–4.57 min. The hydrogel synthesized with 5% w/v of O‐MOG composition exhibited the best characteristics for printability based on rheological assessments, and this composition was used for further printing assessment, where bi‐layered 4 × 4 and 2 × 2 grids were successfully printed using 22 G (0.41 mm) and 23 G (0.34 mm) syringes. All the constructs had a printability index value of 1 ± 0.13 and spreading ratios &lt;6.5, demonstrating the feasibility of employing the synthesized hydrogel as an acellular matrix via additive manufacturing.Highlights Self‐healing hydrogel was prepared by mixing the precursors through a cannula. Rheology was examined using standard tests for printability assessment. 3D printability was achieved using two different gauze syringes. Printability parameters were recorded and analyzed for the constructs.

Structure, ingredient, and function-based biomimetic scaffolds for accelerated healing of tendon-bone interface

BackgroundTendon-bone interface (TBI) repair is slow and challenging owing to its hierarchical structure, gradient composition, and complex function. In this work, enlightened by the natural characteristics of TBI microstructure and the demands of TBI regeneration, a structure, composition, and function-based scaffold was fabricated. Methods: The biomimetic scaffold was designed based on the “tissue-inducing biomaterials” theory: (1) a porous scaffold was created with poly-lactic-co-glycolic-acid, nano-hydroxyapatite and loaded with BMP2-gelatinmp to simulate the bone (BP); (2) a hydrogel was produced from sodium alginate, type I collagen, and loaded with TGF-β3 to simulate the cartilage (CP); (3) the L-poly-lactic-acid fibers were oriented to simulate the tendon (TP). The morphology of tri-layered constructs, gelation kinetics, degradation rate, release kinetics and mechanical strength of the scaffold were characterized. Then, bone marrow mesenchymal stem cells (MSCs) and tenocytes (TT-D6) were cultured on the scaffold to evaluate its gradient differentiation inductivity. A rat Achilles tendon defect model was established, and BMSCs seeded on scaffolds were implanted into the lesionsite. The tendon-bone lesionsite of calcaneus at 4w and 8w post-operation were obtained for gross observation, radiological evaluation, biomechanical and histological assessment. ResultsThe hierarchical microstructures not only endowed the scaffold with gradual composition and mechanical properties for matching the regional biophysical characteristics of TBI but also exhibited gradient differentiation inductivity through providing regional microenvironment for cells. Moreover, the scaffold seeded with cells could effectively accelerate healing in rat Achilles tendon defects, attributable to its enhanced differentiation performance. ConclusionThe hierarchical scaffolds simulating the structural, compositional, and cellular heterogeneity of natural TBI tissue performed therapeutic effects on promoting regeneration of TBI and enhancing the healing quality of Achilles tendon. The translational potential of this articleThe novel scaffold showed the great efficacy on tendon to bone healing by offering a structural and compositional microenvironment. The results meant that the hierarchical scaffold with BMSCs may have a great potential for clinical application.