Hydrogel Microparticles Research Articles

Engineering hemin-loaded hyaluronan needle-like microparticles with photoprotective properties against UV-induced tissue damage.

This study aimed to develop hyaluronan (HA)-based hydrogel microparticles (MPs) loaded with hemin to address the limitations of traditional macroscale hydrogels. The objective is to design MPs such that they can modulate their physicochemical properties. Given the widespread use of ultraviolet C (UVC) light in various industries and the need for protective measures against accidental exposure, this study evaluated the potential of hemin-loaded MPs to protect human dermal fibroblasts from oxidative stress and cell death caused by UVC exposure. Multiple MP formulations were developed and analysed for size, surface charge, swelling behaviour, degradation rate, and radical scavenging capabilities, both with and without hemin loading. The most promising formulations were tested against UVC-exposed cells to assess cell viability, intracellular nitric oxide (˙NO) and reactive oxygen species levels, and protein carbonylation. The fabricated particles were in the form of microneedles, and the degree of their crosslinking and the role of hemin in the chemical crosslinking reaction were found to influence the surface charge and hydrodynamic diameter of the MPs. Increased crosslinking resulted in reduced swelling, slower degradation, and decreased hemin release rate. MPs with a higher degree of swelling were capable of releasing hemin into the culture medium, leading to enhanced bilirubin generation in dermal fibroblasts following cellular uptake. Pre-treatment with these MPs protected the cells from UVC-induced cell death, nitrosative stress, and protein carbonylation. These findings highlight the potential of the studied MPs to release hemin and to minimise the harmful effects of UVC on dermal fibroblasts.

Injectable liposome-containing click hydrogel microparticles for release of macromolecular cargos.

Hydrogel microparticles ranging from 0.1-100 μm, referred to as microgels, are attractive for biological applications afforded by their injectability and modularity, which allows facile delivery of mixed populations for tailored combinations of therapeutics. Significant efforts have been made to broaden methods for microgel production including via the materials and chemistries by which they are made. Via droplet-based-microfluidics we have established a method for producing click poly-(ethylene)-glycol (PEG)-based microgels with or without chemically crosslinked liposomes (lipo-microgels) through the Michael-type addition reaction between thiol and either vinyl-sulfone or maleimide groups. Unifom spherical microgels and lipo-microgels were generated with sizes of 74 ± 16 μm and 82 ± 25 μm, respectively, suggesting injectability that was further supported by rheological analyses. Super-resolution confocal microscopy was used to further verify the presence of liposomes within the lipo-microgels and determine their distribution. Atomic force microscopy (AFM) was conducted to compare the mechanical properties and network architecture of bulk hydrogels, microgels, and lipo-microgels. Further, encapsulation and release of model cargo (FITC-Dextran 5 kDa) and protein (equine myoglobin) showed sustained release for up to 3 weeks and retention of protein composition and secondary structure, indicating their ability to both protect and release cargos of interest.

Facilely printed silk fibroin hydrogel microparticles as injectable long-lasting fillers.

There is a high demand from aging people for facial fillers with desirable biocompatibility and lasting filling effects to overcome facial depression. Novel injectable regenerated silk fibroin (RSF) microparticles were facilely printed from a glycidyl methacrylate-modified silk fibroin hydrogel to address this issue. The β-sheet content and mechanical properties of the RSF hydrogel can be simply modulated by the number of freeze-thawing cycles, and the swelling rate of the RSF hydrogel in saline was negligible. The printed RSF microparticles were uniform, and their diameter was about 300-500 μm, which could be adjusted by the pore sizes of the printed screens. After the injection with a 26-gauge needle, the size distribution of RSF microparticles had no noticeable variation, suggesting that the microparticles could bear the shear strain without breaking during the injection. The in vitro experiments demonstrated that RSF not only had desirable biocompatibility but also facilitated fibroblast migration. The subcutaneous injection experiments demonstrated that the RSF microparticles formed a lasting spot in the injected site. The tissue sections revealed that the RSF microparticles were still distinct on week 8, and blood vessels formed around the microparticles. These promising data demonstrate that the printed RSF microparticles have great potential for facial rejuvenation.

Microfluidics-aided fabrication of 3D micro-nano hierarchical SERS substrate for rapid detection of dual hepatocellular carcinoma biomarkers.

The simultaneous analysis of trace amounts of dual biomarkers is crucial in the early diagnosis, treatment, and prognosis of hepatocellular carcinoma (HCC). In this study, we prepared SERS-active hydrogel microparticles (SAHMs) with 3D hierarchical gold nanoparticles (AuNPs) micro-nanostructures by microdroplet technology and in situ synthesis, which demonstrated high reproducibility and sensitivity. Compared with traditional 2D SERS substrates, this newly prepared 3D SERS substrate provided a high density of nano-wrinkled structures and numerous AuNPs. Furthermore, a newly designed SERS-active substrate was proposed for the simultaneous microfluidic detection of AFP and AFU. The Raman signals of sandwich immunocomplexes on the surface of the SAHMs were measured for the trace analysis of these biomarkers. The proposed microfluidic platform achieved AFP and AFU detection in the range of 0.1-100 ng mL-1 and 0.01-100 ng mL-1, respectively, which represents a good response. Indeed, this platform is easy to fabricate, of low cost and has short detection time and comparable detection limits to other methods. As far as we know, this is the first study to achieve the simultaneous detection of AFP and AFU on a microfluidic platform. Therefore, we proposed a new simultaneous detection platform for dual HCC biomarkers that shows strong potential for the early diagnosis of HCC.

Hydrogel Microparticles for Bone Regeneration.

Hydrogel microparticles (HMPs) stand out as promising entities in the realm of bone tissue regeneration, primarily due to their versatile capabilities in delivering cells and bioactive molecules/drugs. Their significance is underscored by distinct attributes such as injectability, biodegradability, high porosity, and mechanical tunability. These characteristics play a pivotal role in fostering vasculature formation, facilitating mineral deposition, and contributing to the overall regeneration of bone tissue. Fabricated through diverse techniques (batch emulsion, microfluidics, lithography, and electrohydrodynamic spraying), HMPs exhibit multifunctionality, serving as vehicles for drug and cell delivery, providing structural scaffolding, and functioning as bioinks for advanced 3D-printing applications. Distinguishing themselves from other scaffolds like bulk hydrogels, cryogels, foams, meshes, and fibers, HMPs provide a higher surface-area-to-volume ratio, promoting improved interactions with the surrounding tissues and facilitating the efficient delivery of cells and bioactive molecules. Notably, their minimally invasive injectability and modular properties, offering various designs and configurations, contribute to their attractiveness for biomedical applications. This comprehensive review aims to delve into the progressive advancements in HMPs, specifically for bone regeneration. The exploration encompasses synthesis and functionalization techniques, providing an understanding of their diverse applications, as documented in the existing literature. The overarching goal is to shed light on the advantages and potential of HMPs within the field of engineering bone tissue.

On-microparticle construction of endothelialized liver microtissues for drug testing

With the advantage of uniformity and customizability, hydrogel microparticles are widely used to establish in vitro organoid modeling for drug testing. However, the practical values of current strategies are limited by the lack of near-physiological structures and functions. In this work, microparticle-based liver models with biomimetic endothelial barriers are engineered using a simple, biocompatible, and high-throughput method for the application of drug testing. The hepatocyte-laden hydrogel microparticles with a rough surface are prepared using a microfluidic spraying technique, and their surfaces allow for customized protein modifications. Under the action of topological texture and matrigel modifications, the microparticle surface can induce endothelial cell adhesion, extension, and junction, thus generating a continuous, tight monolayer endothelial barrier. Semi-permeability of endothelial barrier and enhanced liver function was demonstrated in the constructed microparticle tissue models. Finally, these models were utilized to reproduce a sensitive inhibitory action of the endothelial barrier on the biotransformation of prodrugs (i.e., tegafur). Overall, microparticle-based endothelialized liver models achieved not only heterotypic cell co-culture but also tissue morphogenesis, which is anticipated to accelerate comprehensive evaluations of the drug biotransformation and improve the translatability of drug testing results from in vitro to in vivo.

Preparation, physicochemical characterization and swelling properties of composite hydrogel microparticles based on gelatin and pectins with different structure

Composite hydrogel microparticles based on pectins with different structures (callus culture pectin (SVC) and apple pectin (AU)) and gelatin were developed. Hydrogel microparticles were formed by the ionotropic gelation and electrostatic interaction of COO− groups of pectin and NH3+ groups of gelatin, which was confirmed by FTIR spectroscopy. The addition of gelatin to pectin-based gel formulations resulted in a decrease in gel strength, whereas increasing gelatin concentration enhanced this effect. The microparticle gel strength increased in proportion to the increase in the pectin concentration. The DSC and TGA analyzes showed that pectin-gelatin gels had the higher thermal stability than individual pectins. The gel strength, Ca2+ content and thermal stability of the microparticles based on gelatin and SVC pectin with a lower degree of methylesterification (DM) (14.8 %) were higher compared to that of microparticles based on gelatin and AU pectin with a higher DM (40 %). An increase in the SVC concentration, Ca2+ content and gel strength of SVC-gelatin microparticles led to a decrease in the swelling degree in simulated gastrointestinal fluids. The addition of 0.5 % gelatin to gels based on AU pectin resulted in increased stability of the microparticles in gastrointestinal fluids, while the microparticles from AU without gelatin were destroyed.

Decellularized Bone Matrix/45S5 Bioactive Glass Biocomposite Hydrogel-Based Constructs with Angiogenic and Osteogenic Properties: Ex Ovo and Ex Vivo Evaluations.

Decellularized extracellular matrix is often used to create an in vivo-like environment that supports cell growth and proliferation, as it reflects the micro/macrostructure and molecular composition of tissues. On the other hand, bioactive glasses (BG) are surface-reactive glass-ceramics that can convert to hydroxyapatite in vivo and promote new bone formation. This study is designed to evaluate the key properties of a novel angiogenic and osteogenic biocomposite graft made of bovine decellularized bone matrix (DBM) hydrogel and 45S5 BG microparticles (10 and 20wt%) to combine the existing superior properties of both biomaterial classes. Morphological, physicochemical, mechanical, and thermal characterizations of DBM and DBM/BG composite hydrogels are performed. Their in vitro biocompatibility is confirmed by cytotoxicity and hemocompatibility analyses. Ex vivo chick embryo aortic arch and ex ovo chick chorioallantoic membrane (CAM) assays reveal that the present pro-angiogenic property of DBM hydrogels is enhanced by the incorporation of BG. Histochemical stainings (Alcian blue and Alizarin red) and digital image analysis of ossification on hind limbs of embryos used in the CAM model reveal the osteogenic potential of biomaterials. The findings support the notion that the developed DBM/BG composite hydrogel constructs have the potential to be a suitable graft for bone repair.

Shaped Magnetogel Microparticles for Multispectral Magnetic Resonance Contrast and Sensing.

Multispectral magnetic resonance imaging (MRI) contrast agents are microfabricated three-dimensional magnetic structures that encode nearby water protons with discrete frequencies. The agents have a unique radiofrequency (RF) resonance that can be tuned by engineering the geometric parameters of these microstructures. Multispectral contrast agents can be used as sensors by incorporating a stimulus-driven shape-changing response into their structure. These geometrically encoded magnetic sensors (GEMS) enable MRI-based sensing via environmentally induced changes to their geometry and their corresponding RF resonance. Previously, GEMS have been made using thin-film lithography techniques in a cleanroom environment. While these approaches offer precise control of the microstructure, they can be a limitation for researchers who do not have cleanroom access or microfabrication expertise. Here, an alternative approach for GEMS fabrication based on soft lithography is introduced. The fabrication scheme uses cheap, accessible materials and simple chemistry to produce shaped magnetic hydrogel microparticles with multispectral MRI contrast properties. The microparticles can be used as sensors by fabricating them out of shape-reconfigurable, "smart" hydrogels. The change in shape causes a corresponding shift in the resonance of the GEMS, producing an MRI-addressable readout of the microenvironment. Proof-of-principle experiments showing a multispectral response to pH change with cylindrical shell-shaped magnetogel GEMS are presented.

Multifunctional Injectable Hydrogel Microparticles Loaded with miR-29a Abundant BMSCs Derived Exosomes Enhanced Bone Regeneration by Regulating Osteogenesis and Angiogenesis.

The study investigated whether both the osteogenic and angiogenic potential of Exos (Exosomes) can be enhanced by overexpression of exosomal miRNA (microRNA) and to confirm whether Exos loaded in HMPs (Hydrogel microparticles) exert long-term effects during new bone formation. BMSCs and Exos are successfully obtained. In vitro and in vivo experiments confirmed that HDAC4 (Histone deacetylase 4) is inhibited by miR-29a overexpression accompanied by the upregulation of RUNX2 (Runt-related transcription factor 2) and VEGF (Vascular Endothelial Growth Factor), thereby enhancing osteogenic and angiogenic capabilities. The HMP@Exo system is synthesized from HB-PEGDA (Hyperbranched Poly Ethylene Glycol Diacrylate)- and SH-HA (Sulfhydryl-Modified Hyaluronic Acid)-containing Exos using a microfluidic technique. The HMP surface is modified with RGD (Arg-Gly-Asp) peptides to enhance cell adhesion. The system demonstrated good injectability, remarkable compatibility, outstanding cell adhesion properties, and slow degradation capacity, and the sustained release of Agomir-29a-Exos (Exosomes derived from Agomir-29a transfected BMSCs) from HMPs enhanced the proliferation and migration of BMSCs and HUVECs (Human Umbilical Vein Endothelial Cells) while promoting osteogenesis and angiogenesis. Overall, the findings demonstrate that the HMP@Exo system can effectively maintain the activity and half-life of Exos, accompanied by overexpression of miR-29a (microRNA-29a). The injectable system provides an innovative approach for accelerating fracture healing by coupling osteogenesis and angiogenesis.

The Effect of Gelatin Source on the Synthesis of Gelatin-Methacryloyl and the Production of Hydrogel Microparticles.

Gelatin methacryloyl (GelMA) is widely used for the formulation of hydrogels in diverse biotechnological applications. After the derivatization of raw gelatin, the degree of functionalization (DoF) is an attribute of particular interest as the functional residues are necessary for crosslinking. Despite progress in the optimization of the process found in the literature, a comparison of the effect of raw gelatin on the functionalization is challenging as various approaches are employed. In this work, the modification of gelatin was performed at room temperature (RT), and eight different gelatin products were employed. The DoF proved to be affected by the bloom strength and by the species of gelatin at an equal reactant ratio. Furthermore, batch-to-batch variability of the same gelatin source had an effect on the produced GelMA. Moreover, the elasticity of GelMA hydrogels depended on the DoF of the protein as well as on bloom strength and source of the raw material. Additionally, GelMA solutions were used for the microfluidic production of droplets and subsequent crosslinking to hydrogel. This process was developed as a single pipeline at RT using protein concentrations up to 20% (w/v). Droplet size was controlled by the ratio of the continuous to dispersed phase. The swelling behavior of hydrogel particles depended on the GelMA concentration.

Curcumin-encapsulated fish gelatin-based microparticles from microfluidic electrospray for postoperative gastric cancer treatment

Gastric cancer is the fifth most frequently diagnosed malignant neoplasm and the third leading cause of cancer-related mortality. Nevertheless, the therapeutic efficacy of conventional surgical and chemotherapeutic interventions in clinical practice is often unsatisfactory. Curcumin (Cur) has shown promise as a therapeutic agent in prior studies. However, its progress in this context has been impeded by challenges including low solubility, instability in aqueous environments, and rapid metabolism. In this study, we develop methacrylate fish gelatin (FGMA) hydrogel microparticles (FGMPs@Cur) encapsulating Cur via microfluidic electrospray technology for postoperative comprehensive treatment of gastric cancer. Comprehensive characterizations and analyses were conducted to assess the cytotoxicity against gastric cancer cells and potential tissue reparative effects of FGMPs@Cur. In vitro experiments revealed that FGMPs@Cur exhibited a remarkable cytotoxic effect on nearly 80 % of gastric cancer cells while maintaining at least 95 % viability of normal cells in cell compatibility tests. In vivo results demonstrated that FGMPs@Cur significantly reduced tumor volume to 47 % of the control group, and notable tissue regeneration was observed at the surgical site. These properties indicated that such a hydrogel microparticle system is a promising candidate for postoperative gastric cancer treatment in practical application.

Fabrication of alginate-based hydrogel microparticle via ruthenium-catalyzed photocrosslinking.

In this study, we developed an alginate-based microparticle production process via sodium ruthenium(II) tris-bipyridyl dication (Ru)/ammonium persulfate (SPS)-mediated visible light crosslinking system using a microfluidic device. Microparticles were prepared by crosslinking phenolic-substituted alginate (AlgPh) and incorporated gelatin (GelPh) in an aqueous solution containing SPS, which flowed into an ambient immiscible liquid paraffin-containing Ru using coaxial double orifice microfluidic device. The hydrogel microparticles appeared with the desired geometries and dimensions under optimal conditions. The concentration of AlgPh and light intensity were the most critical parameters for harvesting spherical microparticles with homogeneous size distribution. The physical properties of the prepared AlgPh microparticles were characterized and compared with Alg-Ca microparticles. Cell viability and proliferation preserved on AlgPh/GelPh hydrogel surfaces. Also, encapsulated cells in microparticles were also viable and proliferated well over 13 days after encapsulation. In brief, the results proved the feasibility of fabricating AlgPh vehicles via Ru/SPS-mediated system and visible light irradiation as a simple and efficient three-dimensional platform, which are applicable for various tissue engineering and cell delivery purposes.

Multilayer Hydrogel Microcubes: Effects of Templating Particle Morphology on Cubic Hydrogel Properties

AbstractNon‐spherical stimuli‐responsive polymeric particles have shown critical importance in therapeutic delivery. Herein, pH‐responsive poly(methacrylic acid) (PMAA) cubic hydrogel microparticles are synthesized by crosslinking PMAA layers within PMAA/poly(N‐vinylpyrrolidone) hydrogen‐bonded multilayers templated on porous inorganic microparticles. This study investigates the effects of template porosity and surface morphology on the PMAA multilayer hydrogel microcube properties. It is found that the hydrogel structure depends on the template's calcination time and temperature. The pH‐triggered PMAA hydrogel cube swelling depends on the hydrogel's internal architecture, either hollow capsule‐like or non‐hollow continuous hydrogels. The loading efficiency of the doxorubicin (DOX) drug inside the microcubes is analyzed by high‐performance liquid chromatography (HPLC), and shows the dependenceof the drug uptake on the network structure and morphology controlled by the template porosity. Varying the template calcination from low (300 °C) to high (1000 °C) temperature results in a 2.5‐fold greater DOX encapsulation by the hydrogel cubes. The effects of hydrogel surface charge on the DOX loading and release are also studied using zeta‐potential measurements. This work provides insight into the effect of structural composition, network morphology, and pH‐induced swelling of the cubical hydrogels and may advance the development of stimuli‐responsive vehicles for targeted anticancer drug delivery.

Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis

Exosomes (Exos) secreted by adipose-derived stem cells (ADSCs) have shown potential in alleviating osteoarthritis (OA). Previous studies indicated that infrapatellar fat pad (IPFP) derived stem cells (IPFSCs) may be more suitable for the treatment of OA than subcutaneous adipose tissue (ScAT) derived stem cells (ScASCs). However, it remains unclear which type of Exos offers superior therapeutic benefit for OA. This study first compared the differences between Exos derived from IPFP stem cells (ExosIPFP) and ScAT stem cells (ExosScAT) in OA treatment. Results suggested that ExosIPFP significantly inhibit the degradation of cartilage extracellular matrix (ECM) than ExosScAT, following this, the differences in microRNA (miRNA) expression between the two types of Exos using small RNA sequencing were performed. Subsequently, miR-99 b-3p was chosen and over-expressed in ExosScAT (ExosScAT−99b−3p), both in vivo and in vitro experiments demonstrated its efficacy in inhibiting the expression of ADAMTS4, promoting the repair of the ECM in OA. Finally, microfluidic technology was performed to fabricate a hyaluronan-based hydrogel microparticles (HMPs) for encapsulating Exos (HMPs@exos), the injectability, sustained release of Exos and long-term therapeutic effect on OA were validated. In summary, these results suggest miR-99 b-3p regulates the degradation of cartilage ECM by targeting ADAMTS4, the upregulation of miR-99 b-3p in ExosScAT would enable them to exhibit comparable or even superior effectiveness to ExosIPFP for OA treatment, making it a promising approach for OA treatment. Considering the abundant resources of ScAT and the limited availability of IPFP, ScAT harvested through liposuction could be genetically engineered to yield Exos for OA treatment. Furthermore, the encapsulation of Exos in HMPs provides an injectable sustained local drug release system, which could potentially enhance the efficacy of Exos and hold potential as future therapeutic strategies.

Improved Humoral Immunity and Protection against Influenza Virus Infection with a 3d Porous Biomaterial Vaccine.

New vaccine platforms that activate humoral immunity and generate neutralizing antibodies are required to combat emerging pathogens, including influenza virus. A slurry of antigen-loaded hydrogel microparticles that annealto form a porous scaffold with high surface area for antigen uptake by infiltrating immune cells as the biomaterial degrades is demonstrated to enhance humoral immunity. Antigen-loaded-microgels elicited a robust cellular humoral immune response, with increased CD4+ T follicular helper (Tfh) cells and prolonged germinal center (GC) B cells comparable to the commonly used adjuvant, aluminum hydroxide (Alum). Increasing the weight fraction of polymer material led to increased material stiffness andantigen-specific antibody titers superior to Alum. Vaccinating mice with inactivated influenza virus loaded into this more highly cross-linked formulation elicited a strong antibody response and provided protection against a high dose viral challenge. By tuning physical and chemical properties, adjuvanticity can be enhanced leading to humoral immunity and protection against a pathogen, leveraging two different types of antigenic material: individual protein antigen and inactivated virus. The flexibility of the platform may enable design of new vaccines to enhance innate and adaptive immune cell programming to generate and tune high affinity antibodies, a promising approach to generate long-lasting immunity.

Construction and functional evaluation of oral long-acting insulin hydrogel microparticles based on physical and chemical double crosslinking

The objective of this study was to enhance the convenience and effectiveness of diabetes treatment by developing hydrogel microparticles as an oral insulin delivery system, aiming to reduce the necessity for frequent treatments. The hydrogel microparticles were prepared with polysaccharides through a combination of physical and chemical crosslinking method, they achieved good results in insulin loading efficiency (70 %), insulin release efficiency (98 %) and sustained release time (>20 h). The effective transmembrane transport was validated using an intestinal epithelial cell model, which demonstrated a continuous hypoglycemic effect lasting from 6 to 26 h in a type 2 diabetes mouse model. Additionally, the relative bioavailability of insulin reached 30.14 ± 2.62 %, representing a significant breakthrough in the field of oral insulin delivery carriers. Furthermore, oral insulin hydrogel exhibited a substantial improvement in insulin resistance, organ damage, and diabetes-related complications stemming from hyperglycemia. These compelling findings underscore the potential of hydrogel microparticles as a cost-effective and valuable strategy for oral drug delivery in diabetes treatment.

Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in Mice.

Poor tendon-bone interface (TBI) integration is one of the major causes contributing to unsatisfactory healing quality in patients after anterior cruciate ligament (ACL) reconstruction. Type H vessels have been recently found to closely modulate bone formation via regulation of the osteo-angiogenic crosstalk, so the strategies favoring type H vessel formation may be promising therapeutic approaches for improved graft osteointegration. In this study, we reported for the first time the treatment outcome of slit guidance ligand 3 (slit3), a novel proangiogenic factor favoring type H vessel formation, in TBI healing in mice with ACL reconstruction. The mice (n = 87) were divided into three groups for various treatments: hydrogel microparticles (HMP, control group), slit3@HMP, and slit3 neutralizing antibody@HMP (slit3-AB@HMP). Histological analysis, gait performance, radiographic measurement, and biomechanical testing were performed to assess the TBI healing quality. Increased bony ingrowth and reduced fibrous scar tissue was formed at the TBI in the slit3@HMP group when compared to the HMP group. Meanwhile, the slit3-AB@HMP inhibited the osseous ingrowth and increased fibrous scar tissue formation relative to the HMP group. Compared to the HMP group, the slit3@HMP favored type H vessel formation at the TBI while the slit3-AB@HMP impeded it. According to micro-CT assessment, compared to the HMP group, the slit3@HMP significantly increased the peri-tunnel bone mass while the slit3-AB@HMP significantly reduced the peri-tunnel bone mass. The mice in the slit3@HMP group showed the best gait performance in terms of stance time, stride length, paw print area, and stance pressure. Dynamic laxity measurement and tensile testing showed the slit3@HMP group exhibited significantly reduced laxity displacement and improved failure load and stiffness relative to the other two groups. Collectively, the injection of slit3 could be used to enhance tendon-bone integration, which may be ascribed to modulation of angiogenesis-osteogenesis crosstalk coupled by type H vessels.

Pre‐Crosslinking with Hydrogel Microparticles Enhances the Printability of Alginate‐Based Inks

AbstractThe main challenge in extrusion‐based bioprinting is to develop inks which must comprise a manifold of characteristics before, during, and after printing. To tackle the challenge of good shape fidelity and printability of low concentration inks, in this study hydrogel microparticles (HMPs) are proposed to produce internally pre‐crosslinked inks. Alginate (Alg) and oxidized alginate (OA)‐based HMPs are fabricated and used as Ca2+‐releasing reservoirs. OA HMPs are used to demonstrate the versatility of this approach and to show its suitability also for chemically modified alginate. Embedded in either fresh Alg or OA solution, HMPs are used to pre‐crosslink the inks. Rheological measurements revealed that HMP pre‐crosslinking increases the yield stress and viscosity while reducing the loss angle of bioinks. Moreover, printing experiments reveal that being able to tailor rheological properties is an effective tool to improve printability. Furthermore, pre‐crosslinking significantly alters the hydogel internal microstructure. In vitro studies show that NIH/3T3 cells proliferate in HMP pre‐crosslinked bioinks modified with gelatin. Altogether, a low‐cost and easy to use setup to prepare HMPs is presented and for the first time, the possibility of using such HMPs as pre‐crosslinking agent to tailor the printability of alginate‐based bioinks is demonstrated.

The impact of tribometer motion and surface roughness on the frictional regimes of model foods

Assessing the tribological behavior of soft materials is often challenging due to the deformative nature of the surfaces which influences the lubricant entrainment and the contact area. The surface roughness and the tribological motion (e.g. sliding, rotational) of the tribometer may also influence the contact area, surface deformation and fluid entrainment. In the present work, we uncover how the above-mentioned parameters influence the lubrication behavior of Newtonian lubricants and of hydrogel microparticle suspensions. Unique to this study is that we use four different tribometers to obtain a more complete picture of the effect of tribometer characteristics on the frictional behavior. We present a side-by-side analysis of four tribological devices: three commercially available tribometers (Anton Paar, Bruker, PCS Instruments) and a custom-made 3D-printed tribometer. With this qualitative analysis, we demonstrate how the different Stribeck regimes are influenced by tribometer motions. The friction coefficients in the boundary regime and the length of the regime are strongly influenced the tribometer used while the slope in the mixed regime only shows minor differences for different tribometers. In the EHL regime, the slopes found correspond with the theoretically predicted value of 0.5 for the rotational tribometers. The linearly oscillating tribometer, however, displays an additional increase beyond the EHL regime with a much steeper slope than expected, which is caused by the specific motion of the tribometer. We further confirm the influence of tribometer motion by introducing hydrogel particle suspensions as model foods; each tribometer shows different lubrication regimes that are specific for each of the devices, highlighting the system dependency of tribological measurements.