Hydrogel Degradation Research Articles

Acrylate-Based PEG Hydrogels with Ultrafast Biodegradability for 3D Cell Culture.

Poly(ethylene glycol) (PEG)-based hydrogels are particularly challenging to degrade, which hinders efficient cell harvesting within the gel matrix. Here, highly branched copolymers of PEG methyl ether acrylate (PEGMA) and disulfide diacrylate (DSDA) (PEG-DS) with short primary chains and multiple pendent vinyl groups were synthesized by a "vinyl oligomer combination" approach. PEG-DS readily cross-links with thiolated gelatin (Gel-SH) to form hydrogels. Results demonstrate that shortening the primary chains of PEG-DS significantly enhances the viability of bone marrow mesenchymal stem cells (BMSCs) by up to 193.2%. Importantly, DS junctions can be easily cleaved into short primary chains using dithiothreitol (DTT), triggering ultrafast degradation of PEG-DS/Gel-SH hydrogels within 2 min under mild conditions and release of the encapsulated BMSCs. This study establishes a novel strategy to enhance the degradation of acrylate-based PEG hydrogels for three-dimensional (3D) cell culture and harvesting. These findings expand the potential applications of such hydrogels in various biomedical fields.

Injectable Biodegradable Chitosan-PEG/PEG-Dialdehyde Hydrogel for Stem Cell Delivery and Cartilage Regeneration.

Stem cell-based therapy holds promise for cartilage regeneration in treating knee osteoarthritis (KOA). Injectable hydrogels have been developed to mimic the extracellular matrix (ECM) and facilitate stem cell growth, proliferation, and differentiation. However, these hydrogels face limitations such as poor mechanical strength, inadequate biocompatibility, and suboptimal biodegradability, collectively hindering their effectiveness in cartilage regeneration. This study introduces an injectable, biodegradable, and self-healing hydrogel composed of chitosan-PEG and PEG-dialdehyde for stem cell delivery. This hydrogel can form in situ by blending two polymer solutions through injection at physiological temperature, encapsulating human adipose-derived stem cells (hADSCs) during the gelation process. Featuring a 3D porous structure with large pore size, optimal mechanical properties, biodegradability, easy injectability, and rapid self-healing capability, the hydrogel supports the growth, proliferation, and differentiation of hADSCs. Notably, encapsulated hADSCs form 3D spheroids during proliferation, with their sizes increasing over time alongside hydrogel degradation while maintaining high viability for at least 10 days. Additionally, hADSCs encapsulated in this hydrogel exhibit upregulated expression of chondrogenic differentiation genes and proteins compared to those cultured on 2D surfaces. These characteristics make the chitosan-PEG/PEG-dialdehyde hydrogel-stem cell construct suitable for direct implantation through minimally invasive injection, enhancing stem cell-based therapy for KOA and other cell-based treatments.

Tricalcium phosphate-loaded injectable hydrogel as a promising osteogenic and bactericidal teicoplanin-delivery system for osteomyelitis treatment: An in vitro and in vivo investigation

Osteomyelitis is an inflammation of bone tissue usually caused by pyogenic bacteria. The most recurrent clinical approach consists of bone debridement followed by parenteral administration of antibiotics. However, systemic antibiotic treatment has limitations regarding absorption rate and bioavailability over time. The main challenge of osteomyelitis treatment consists of coupling the persistent infection treatment with the regeneration of the bone debrided. In this work, we developed an injectable drug delivery system based on poloxamer 407 hydrogel containing undoped Mg, Zn-doped tricalcium phosphate (β-TCP), and teicoplanin, a broad-spectrum antibiotic. We evaluated how the addition of teicoplanin and β-TCP affected the micellization, gelation, particle size, and surface charge of the hydrogel. Later, we studied the hydrogel degradation and drug delivery kinetics. Finally, the bactericidal, biocompatibility, and osteogenic properties were evaluated through in vitro studies and confirmed by in vivo Wistar rat models. Teicoplanin was found to be encapsulated in the corona portions of the hydrogel micelles, yielding a bigger hydrodynamics radius. The encapsulated teicoplanin showed a sustained release over the evaluated period, enough to trigger antibacterial properties against Gram-positive bacteria. Besides, the formulations were biocompatible and showed bone healing ability and osteogenic properties. Finally, in vivo studies confirmed that the proposed locally injected formulations yielded osteomyelitis treatment with superior outcomes than parenteral administration while promoting bone regeneration. In conclusion, the presented formulations are promising drug delivery systems for osteomyelitis treatment and deserve further technological improvements.

Degradable Cell-Adhesive Hybrid Hydrogels by Cross-Linking of Gelatin with Poly(2-isopropenyl-2-oxazoline).

This study focused on the cross-linking of poly(2-isopropenyl-2-oxazoline) (PiPOx) with gelatin to obtain strong, degradable hybrid hydrogels with good cell adhesion. The molecular weight and concentration of PiPOx and the PiPOx-to-gelatin ratio were varied to adjust the mechanical and swelling properties of the hybrid hydrogels. The swelling degree of PiPOx-gelatin hydrogels in water ranged between 1260 and 810%, with the corresponding Young's compressive moduli ranging from 77 to 215 kPa. Rheological measurements demonstrated the mechanical stability of the hydrogels. The hydrogels exhibited substantial degradation in Dulbecco's phosphate-buffered saline (DPBS) and cell culture medium within several weeks, indicating their degradability and responsiveness. The cell adhesion assay with primary human foreskin fibroblasts revealed the hybrid hydrogels are noncytotoxic and support cell attachment and proliferation. These strong hydrogels thus show excellent potential as biomedical cell scaffolds, combining the tunability and strength of PiPOx hydrogels with gelatin's cell-interactive properties while the ester-containing cross-links provide tunable degradability.

Computational modeling of cell motility and clusters formation in enzyme-sensitive hydrogels

In this paper, we propose an extension of a previous model of cell motility in tissue engineering applications recently developed by the authors. Achieving large-scale production of neo-tissue through biofabrication technologies remains challenging owing to the need of thoroughly optimizing all the relevant process variables, a task hardly attainable through solely trial and error approaches. Therefore, the present work is intended to provide a valid and effective computational-based support for neo-tissue formation, with a specific focus on the preliminary phase of such process, in which cells move through a polymeric scaffold (hydrogel) and then compact into clusters. Cell motility is modeled by resorting to the phase-field method, and by incorporating diffusion of nutrients from the external culture bath as well as the expression by cells of chemoattractant substances that bias the random path they otherwise would follow. The previous model has been enriched by additionally encompassing the secretion of enzymes by cells that cleave the crosslinks between the hydrogel polymer chains. As such, in the present model hydrogel degradation exhibits spatio-temporal variations in its chemo-physical properties related to the local amount of enzymes, which deeply affects cell motility. Numerical results showcase the pivotal importance of the cells micro-environment properties for their crawling in hydrogel scaffolds, opening towards the development of a predictive computational-aided optimization tool for neo-tissue growth in bioprinted scaffolds.

Tunable gelatin methacrylate polyethylene glycol diacrylate hydrogels for cell mechanosensing applications

Three-dimensional (3D) tissue-engineered scaffolds mimic the physiological environment of cells by providing essential structural support, biochemical cues, and the mechanical strength needed for cell adhesion, proliferation, migration, and differentiation. Hydrogels like polyethylene glycol diacrylate (PEGDA) are commonly used biomaterials for cell culture due to their affordability, tunable stiffness, and ability to efficiently transport nutrients and gases. However, PEGDA lacks cell adhesion sites essential for cell proliferation and migration and has limited degradability. Methacrylated gelatin (GelMA) produced from denatured bovine collagen, crosslinks under ultraviolet light (UV) resulting in a degradable hydrogel with cell adhesion sites. Here, we synthesized GelMA with variable degree of methacrylation and crosslinked it with PEGDA to produce cell scaffolds with independently tunable mechanical and biochemical properties by varying the ratios of the two polymers. We determined polymer ratios that resulted in scaffolds with different mechanical properties but the same gelatin concentrations (providing cell adhesion and degradation sites) as well as different gelatin concentrations but the same mechanical properties. With the developed scaffold library, we further used a design of experiments approach to probe the parameter space and perform detailed analysis on chemical composition-scaffold properties as well as scaffold properties-cell behavior correlations. Our findings showed that hydrogel properties such as modulus, swelling, pore size, and permeability, strongly depended on total polymer concentration and not on the GelMA fraction. GelMA significantly influenced cell spreading, while addition of any amount of PEGDA delayed cell spreading significantly. We suggest that such analysis will broaden the utility of the GelMA/PEGDA hydrogels, presenting a versatile platform for mechanosensing research in 3D environments.

Self-Assembled DNA Microflowers for Platelet-Derived Extracellular Vesicle Isolation and Infected Wound Healing.

Platelet-derived extracellular vesicles (PEVs) showing great potential in wound healing have attracted increasing attention recently. Nondestructive isolation and effective utilization strategies are highly conducive for PEVs developing into recognized therapeutic entities. Here, we present an efficient strategy for PEV isolation and bacterial infected wound healing based on self-assembled DNA microflowers. First, DNA microflowers are prepared using rolling circle amplification. Then, the hydrophobic interaction between cholesteryl modified on DNA microflowers and the phospholipid bilayer membrane of PEVs leads to the formation of a network structure with improved mechanical strength and the separation of PEVs from biological samples. Finally, controlled release of PEVs is achieved through bacterial-induced hydrogel degradation. In vitro experiments demonstrate the obtained DNA hydrogel with good cytocompatibility and therapeutic potential. Taken together, the DNA microflower-based hydrogels with bioadhesive, self-healing, tunable mechanical properties and bacteria-responsive behavior offer substantial potential for EV isolation and wound healing.

Formation of Zwitterionic and Self-Healable Hydrogels via Amino-yne Click Chemistry for Development of Cellular Scaffold and Tumor Spheroid Phantom for MRI.

In situ-forming biocompatible hydrogels have great potential in various medical applications. Here, we introduce a pH-responsive, self-healable, and biocompatible hydrogel for cell scaffolds and the development of a tumor spheroid phantom for magnetic resonance imaging. The hydrogel (pMAD) was synthesized via amino-yne click chemistry between poly(2-methacryloyloxyethyl phosphorylcholine-co-2-aminoethylmethacrylamide) and dialkyne polyethylene glycol. Rheology analysis, compressive mechanical testing, and gravimetric analysis were employed to investigate the gelation time, mechanical properties, equilibrium swelling, and degradability of pMAD hydrogels. The reversible enamine and imine bond mechanisms leading to the sol-to-gel transition in acidic conditions (pH ≤ 5) were observed. The pMAD hydrogel demonstrated potential as a cellular scaffold, exhibiting high viability and NIH-3T3 fibroblast cell encapsulation under mild conditions (37 °C, pH 7.4). Additionally, the pMAD hydrogel also demonstrated the capability for in vitro magnetic resonance imaging of glioblastoma tumor spheroids based on the chemical exchange saturation transfer effect. Given its advantages, the pMAD hydrogel emerges as a promising material for diverse biomedical applications, including cell carriers, bioimaging, and therapeutic agent delivery.

Probing the Effects of Chirality on Self-Assembling Peptides: Hydrogel Formation, Degradation, Antigen Release, and Adjuvancy.

Multidomain peptides (MDPs) are amino acid sequences that self-assemble to form supramolecular hydrogels under physiological conditions that have shown promise for a number of biomedical applications. K2(SL)6K2 ("K2"), a widely studied MDP, has demonstrated the ability to enhance the humoral immune response to co-delivered antigen. Herein, we sought to explore the in vitro and in vivo properties of a peptide with the same sequence but opposite chirality (D-K2) since peptides composed of D-amino acids are resistant to protease degradation and potentially more immunostimulatory than their canonical counterparts. K2 and D-K2 hydrogels were characterized and evaluatedin vitro usingcircular dichroism, rheology, cryo-electron microscopy, andfluorescence recovery after photobleaching studies. In vivo experiments in SKH-1 mice were conducted to evaluateboth ovalbumin release from the hydrogels andhydrogel degradation. The injection site of the hydrogels was analyzed using histologyandhumoral immunity was assessed byELISA. In vitro, the enantiomeric hydrogels exhibited similar rheological properties, and fluorescence recovery after photobleaching experiments demonstrated that the diffusion of ovalbumin (OVA), a model antigen, was similar within both hydrogels. In vivo, K2 and D-K2 peptide hydrogels had similar OVA release rates, both releasing 89% of the antigen within 8days. Both hydrogels elicited a similar antigen-specific humoral immune response. However, the in vivo degradation of the D-K2 hydrogel progressed significantly slower than K2. After 4weeks in vivo, only 23 ± 7% of the K2 hydrogel remained at the injection site compared to 94 ± 7% of the D-K2 hydrogel, likely due to their different protease susceptibilities. Taken together, these data suggest that peptide chirality can be a useful tool for increasing hydrogel residence time for biomedical applications that would benefit from long persistence times and that, if an antigen releases over a sufficiently short period, release can be largely independent of degradation rate, though slower-diffusing payloads may exhibit degradation rate dependence. The online version contains supplementary material available at 10.1007/s12195-024-00806-1.

The application of pH-responsive hyaluronic acid-based essential oils hydrogels with enhanced anti-biofilm and wound healing

pH could play vital role in the wound healing process due to the bacterial metabolites, which is one essential aspect of desirable wound dressings lies in being pH-responsive. This work has prepared a degradable hyaluronic acid hydrogel dressing with wound pH response-ability. The aldehyde-modified hyaluronic acid (AHA) was obtained, followed by complex mixture formation of eugenol and oregano antibacterial essential oil in the AHA-CMCS hydrogel through the Schiff base reaction with carboxymethyl chitosan (CMCS). This hydrogel composite presents pH-responsiveness, its disintegration mass in acidic environment (pH = 5.5) is 4 times that of neutral (pH = 7.2), in which the eugenol release rate increases from 37.6 % to 82.1 %. In vitro antibacterial and in vivo wound healing investigations verified that hydrogels loaded with essential oils have additional 5 times biofilm removal efficiency, and significantly accelerate wound healing. Given its excellent anti-biofilm and target-release properties, the broad application of this hydrogel in bacteria-associated wound management is anticipated.

Light-Operated Transient Unilateral Adhesive Hydrogel for Comprehensive Prevention of Postoperative Adhesions.

Dislocation of anti-adhesion materials, non-specific tissue adhesion, and the induction of secondary fibrinolysis disorders are the main challenges faced by postoperative anti-adhesion materials. Herein, a self-leveling transient unilateral adhesive hydrogel is custom-designed to conquer these challenges with a theoretically calculated and dual-step tailored gellan gum (GG) as the sole agent. First, the maximum gelation temperature of GG is lowered from 42-25°C through controlled perturbation of intra- and inter-molecular hydrogen bonds, which is achieved by employing the methacrylic anhydride as a "hydrogen bond's perturbator" to form methacrylate GG (MeGG). Second, the "self-leveling" injectability and wound shape adaptably are endowed by the formation of borate-diol complexed MeGG (BMeGG). Finally, the transient unilateral tissue-adhesive hydrogel (BMeGG-H) barrier is prepared through photo-controlled cross-linking of reactive alkenyl groups. This degradable hydrogel demonstrates favorable rheological properties, light-controlled unilateral adhesion properties, biocompatibility, anti-fibrin adhesion, and anti-cell adhesion properties in vitro. Comprehensive regulation of the fibrinolysis balance toward non-adhesion is conformed in a rat model after intra-abdominal surgery via anti-autoinflammatory response, intestinal wall integrity repair, and Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) balance adjustment. Notably, the 14th day anti-adhesion effective rate is 100%, indicating its significant potential in clinical applications for postoperative anti-adhesion.

Degradable and Recyclable Hydrogels for Sustainable Bioelectronics.

Hydrogel bioelectronics has been widely used in wearable sensors, electronic skin, human-machine interfaces, and implantable tissue-electrode interfaces, providing great convenience for human health, safety, and education. The generation of electronic waste from bioelectronic devices jeopardizes human health and the natural environment. The development of degradable and recyclable hydrogels is recognized as a paradigm for realizing the next generation of environmentally friendly and sustainable bioelectronics. This review first summarizes the wide range of applications for bioelectronics, including wearable and implantable devices. Then, the employment of natural and synthetic polymers in hydrogel bioelectronics is discussed in terms of degradability and recyclability. Finally, this work provides constructive thoughts and perspectives on the current challenges toward hydrogel bioelectronics, providing valuable insights and guidance for the future evolution of sustainable hydrogel bioelectronics.

Fibrin Hydrogels Reinforced by Reactive Microgels for Stimulus-Triggered Drug Administration.

Tissue engineering is a steadily growing field of research due to its wide-ranging applicability in the field of regenerative medicine. Application-dependent mechanical properties of a scaffold material as well as its biocompatibility and tailored functionality represent particular challenges. Here the properties of fibrin-based hydrogels reinforced by functional cytocompatible poly(N-vinylcaprolactam)-based (PVCL) microgels are studied and evaluated. The employment of temperature-responsive microgels decorated by epoxy groups for covalent binding to the fibrin is studied as a function of cross-linking degree within the microgels, microgel concentration, as well as temperature. Rheology reveals a strong correlation between the mechanical properties of the reinforced fibrin-based hydrogels and the microgel rigidity and concentration. The incorporated microgels serve as cross-links, which enable temperature-responsive behavior of the hydrogels, and slow down the hydrogel degradation. Microgels can be additionally used as carriers for active drugs, as demonstrated for dexamethasone. The microgels' temperature-responsiveness allows for triggered release of payload, which is monitored using a bioassay. The cytocompatibility of the microgel-reinforced fibrin-based hydrogels is demonstrated by LIVE/DEAD staining experiments using human mesenchymal stem cells. The microgel-reinforced hydrogels are a promising material for tissue engineering, owing to their superior mechanical performance and stability, possibility of drug release, and retained biocompatibility.

Antiinflammatory and antibacterial polytetrahydropyrimidine loaded on degradable thermosensitive hydrogels for treatment of open wounds

Open wound is one of the concerns of modern medicine. The early wound has not been closed, there will be easy to enter the bacteria leading to bacterial infection. When the wound deteriorates further, the inflammation at the wound will continue to strengthen, and eventually become a chronic wound or non-healing wound. Therefore, an antibacterial anti-inflammatory tissue recovery environment will greatly promote the wound healing process. In this work, we prepared a hyaluronic acid/gelatin hydrogel that provides a comfortable recovery environment for wound healing. We also synthesized an anti-bacterial and anti-inflammatory polytetrahydropyrimidine (PTHP) polymer and loaded it into the hydrogel. The PTHP can be released in the hydrogel at a human body temperature of 37 °C, thereby achieving bactericidal and anti-inflammatory effects on the wound. Moreover, the hyaluronic acid/gelatin hydrogel can be degraded automatically at 37 °C. Therefore, PTHP-loaded hyaluronic acid/gelatin hydrogel system is an open wound care material with antibacterial, anti-inflammatory and microenvironment-responsive tissue recovery environment. It is an ideal candidate for the treatment of open wounds.

Preparation and degradability of novel cross-linked functional hydrogels from enzymatic synthesized α-1,3-glucan and its carboxymethyl derivative

Abstract In this research, we prepared novel hydrogels from enzymatically synthesized α-1,3-glucan and its carboxymethyl derivative by crosslinking with ethylene glycol diglycidyl ether. The resulting hydrogels were highly swellable and pH-sensitive with an enhanced highly developed structure and showed excellent protein/dye adsorption performances. Furthermore, the hydrogels had good biodegradability and could be degraded in soil extract solution. Herein, the prepared hydrogels have potential applications as a green and environmentally friendly adsorbent for the effective removal of organic dyes in printing and dyeing wastewater.

Cascade catalysis nanozyme for interfacial functionalization in combating implant infections associated with diabetes via sonodynamic therapy and adaptive immune activation

Innovative solutions are required for the intervention of implant associated infections (IAIs), especially for bone defect patients with chronic inflammatory diseases like diabetes mellitus (DM). The complex immune microenvironment of infections renders implants with direct antibacterial ability inadequate for the prolonged against of bacterial infections. Herein, a synergistic treatment strategy was presented that combined sonodynamic therapy (SDT) with adaptive immune modulation to treat IAIs in diabetes patients. A multifunctional coating was created on the surface of titanium (Ti) implants, consisting of manganese dioxide nanoflakes (MnO2 NFs) with cascade catalytic enzyme activity and a responsive degradable hydrogel containing a sonosensitizer. The reactive oxygen species (ROS) generated by glucose-hydrogen peroxide (H2O2) cascade catalysis and ultrasound (US) activation sonosensitizer helped kill bacteria and release bacterial antigens. Meanwhile, Mn2+ facilitated dendritic cells (DCs) maturation, enhancing antigen presentation to activate both cellular and humoral adaptive immunity against bacterial infections. This approach effectively eliminated bacteria in established diabetic IAIs model and activated systemic antibacterial immunity, providing long-term antibacterial protection. This study presents a non-antibiotic immunotherapeutic strategy for fighting IAIs in chronic diseases.

Dual Functionalization of Hyaluronan Dermal Fillers with Vitamin B3: Efficient Combination of Bio-Stimulation Properties with Hydrogel System Resilience Enhancement.

Hyaluronic acid (HA) hydrogels are commonly used for facial dermal filling and for alternative medical aesthetic purposes. High diversity exists in commercial formulations, notably for the optimization of finished product stability, functionality, and performance. Polyvalent ingredients such as calcium hydroxylapatite (CaHA) or vitamin B3 (niacinamide) are notably used as bio-stimulants to improve skin quality attributes at the administration site. The aim of the present study was to perform multi-parametric characterization of two novel cross-linked dermal filler formulas (HAR-1 "Instant Refine" and HAR-3 "Maxi Lift") for elucidation of the various functional impacts of vitamin B3 incorporation. Therefore, the HAR products were firstly comparatively characterized in terms of in vitro rheology, cohesivity, injectability, and resistance to chemical or enzymatic degradation (exposition to H2O2, AAPH, hyaluronidases, or xanthine oxidase). Then, the HAR products were assessed for cytocompatibility and in vitro bio-stimulation attributes in a primary dermal fibroblast model. The results showed enhanced resilience of the cohesive HAR hydrogels as compared to JUVÉDERM® VOLBELLA® and VOLUMA® reference products in a controlled degradation assay panel. Furthermore, significant induction of total collagen synthesis in primary dermal fibroblast cultures was recorded for HAR-1 and HAR-3, denoting intrinsic bio-stimulatory effects comparable or superior to those of the Radiesse® and Sculptra™ reference products. Original results of high translational relevance were generated herein using robust and orthogonal experimental methodologies (hydrogel degradation, functional benchmarking) and study designs. Overall, the reported results confirmed the dual functionalization role of vitamin B3 in cross-linked HA dermal fillers, with a significant enhancement of hydrogel system stability attributes and the deployment of potent bio-stimulatory capacities.

Extrusion-based bioprinting: considerations toward gelatin-alginate bioink

PurposeThis study aims to develop a simplified bioink preparation method that can be applied to most hydrogel bioinks used in extrusion-based techniques.Design/methodology/approachThe parameters of the bioprinting process significantly affect the printability of the bioink and the viability of cells. In turn, the bioink formulation and its physicochemical properties may influence the appropriate range of printing parameters. In extrusion-based bioprinting, the rheology of the bioink affects the printing pressure, cell survival and structural integrity. Three concentrations of alginate-gelatin hydrogel were prepared and printed at three different flow rates and nozzle gauges to investigate the print parameters. Other characterizations were performed to evaluate the hydrogel structure, printability, gelation time, swelling and degradation rates of the bioink and cell viability. An experimental design was used to determine optimal parameters. The analyses included live/dead assays, rheological measurements, swelling and degradation.FindingsThe experimental design results showed that the hydrogel flow rate substantially influenced printing accuracy and pressure. The best hydrogel flow rate in this study was 10 ml/h with a nozzle gauge of 18% and 4% alginate. Three different concentrations of alginate-gelatin hydrogels were found to exhibit shear-thinning behavior during printing. After seven days, 46% of the structure in the 4% alginate-5% gelatin sample remained intact. After printing, the viability of skin fibroblast cells for the optimized sample was 91%.Originality/valueThis methodology offers a straightforward bioink preparation method applicable to the majority of hydrogels used in extrusion-based procedures. This can also be considered a prerequisite for cell printing.

Injectable, stable, and biodegradable hydrogel with platelet-rich plasma induced by l-serine and sodium alginate for effective treatment of intrauterine adhesions

The combination of pharmacological and physical barrier therapy is a highly promising strategy for treating intrauterine adhesions (IUAs), but there lacks a suitable scaffold that integrates good injectability, proper mechanical stability and degradability, excellent biocompatibility, and non-toxic, non-rejection therapeutic agents. To address this, a novel injectable, degradable hydrogel composed of poly(ethylene glycol) diacrylate (PEGDA), sodium alginate (SA), and l-serine, and loaded with platelet-rich plasma (PRP) (referred to as PSL-PRP) is developed for treating IUAs. l-Serine induces rapid gelation within 1 min and enhances the mechanical properties of the hydrogel, while degradable SA provides the hydrogel with strength, toughness, and appropriate degradation capabilities. As a result, the hydrogel exhibits an excellent scaffold for sustained release of growth factors in PRP and serves as an effective physical barrier. In vivo testing using a rat model of IUAs demonstrates that in situ injection of the PSL-PRP hydrogel significantly reduces fibrosis and promotes endometrial regeneration, ultimately leading to fertility restoration. The combined advantages make the PSL-PRP hydrogel very promising in IUAs therapy and in preventing adhesions in other internal tissue wounds.

Electrochemical analysis of Ca2+ based on DNAzyme catalyzed degradation of DNA hydrogel

Calcium ion is a type of indispensable metal elements in biology, which participates in processes like maintaining the excitability of neuromuscular muscles. However, calcium content should be monitored in a safety range. Herein, a novel electrochemical method is developed for Ca2+ assay by monitoring electrochemical response after DNAzyme catalyzed DNA hydrogel degradation. Pure DNA hydrogel is first built with three-way junction scaffolds and linkers containing Ca2+-dependent DNAzyme sequence. In the presence of target Ca2+, the substrates in linkers are cleaved and DNA hydrogel can be degraded gradually. The encapsulated electrochemical species thus facilely interact with the electrode, leading to the increase of electrochemical responses. This electrochemical method for Ca2+ quantification is selective and sensitive, which also performs satisfactorily challenging biological samples like sweat and urine.