Degradation Rate Of Hydrogels Research Articles

Drug sustained release from degradable drug-loaded in-situ hydrogels in the posterior eye: A mechanistic model and analytical method

Biodegradable in-situ hydrogels as drug release carriers injected into the eye can treat Neovascular age-related macular degeneration (NV-AMD). Obviously, the biodegradation behavior of hydrogels affects the drug diffusion process in the eye, which can influence the drug concentration distribution and development in the macula. Herein, the intraocular diffusion process of the drugs which are released from the biodegradable hydrogel was studied by using finite element method, with the effect of the biodegradation behavior of hydrogels on the drug release process was considered. The effects of the initial average mesh size, rate constant of biodegradation, and position of hydrogels on the drug release process were analyzed. The results showed that the biodegradation behavior of hydrogels decreases the drug release rate by gradually expanding the mesh size, prolonging the duration of drug treatment in the macula. The biodegradable hydrogels’ position, initial mesh size, and biodegradation rate constant also affect drug delivery. Different locations of hydrogels denote different distances between the drug and macula, which affects the diffusion time and further influence the macular drug concentration. The initial mesh size alters the initial drug release rate, which affects the duration of hydrogels’ drug release process and drug concentration and duration in the macula. The hydrogel degradation rate affects the development of its mesh size, which affects the drug diffusion in hydrogels, and further affects the drug concentration in the macular region.

Molecular dynamics simulations can predict the optimum drug loading amount in pectin hydrogels for controlled release

Determining an optimum drug concentration to modulate drug release from a flexible and dynamic system, such as hydrogels requires an extensive amount of experiments consuming time and money. Here, we conduct molecular dynamics (MD) simulations to predict an optimum drug concentration to load on low-methoxyl pectin hydrogels, which can maintain the structural integrity and achieve controlled drug release. Systems of low-methoxyl pectin hydrogel modeled as poly-galacturonic acid (PGAL) oligomers cross-linked with Ca2+ and procaine at different concentrations (0, 6, 30, 60, 90, 180 mg procaine/g hydrogel) are investigated. First, a series of 200 ns long all-atom MD simulations in explicit water with replicas are conducted reaching a total simulation time of 3.6 µs. We then assess our predictions with procaine release experiments from low-methoxyl pectin hydrogels, and calculation of storage G' and loss G'' moduli of hydrogel samples. Local and global motions of cross-linked PGAL oligomers from simulation trajectories are analyzed in detail to predict an optimum procaine concentration of 30 mg/g hydrogel. At this loading amount, polymer fluctuations are stabilized and initial monomer neighbors are maintained with a low average distance deviation of 1.5 Å so as to yield an intact hydrogel network. Results from MD simulations and experiments strongly agree. Pectin hydrogels loaded with 30 mg procaine /g have a low hydrogel degradation rate 0.001 g/min and a controlled in vitro drug release when compared to other samples, releasing all 30 mg of loaded procaine from 670 mg hydrogel in 24 h. Results indicate that drug release from the flexible host is mainly controlled by local and global motions of the polymer chains and non-bonded interactions between the system components. The computational approach taken here can be highly useful for similar polymer-based drug delivery systems.

Engineering of Injectable Antibiotic-laden Fibrous Microparticles Gelatin Methacryloyl Hydrogel for Endodontic Infection Ablation.

This study aimed at engineering cytocompatible and injectable antibiotic-laden fibrous microparticles gelatin methacryloyl (GelMA) hydrogels for endodontic infection ablation. Clindamycin (CLIN) or metronidazole (MET) was added to a polymer solution and electrospun into fibrous mats, which were processed via cryomilling to obtain CLIN- or MET-laden fibrous microparticles. Then, GelMA was modified with CLIN- or MET-laden microparticles or by using equal amounts of each set of fibrous microparticles. Morphological characterization of electrospun fibers and cryomilled particles was performed via scanning electron microscopy (SEM). The experimental hydrogels were further examined for swelling, degradation, and toxicity to dental stem cells, as well as antimicrobial action against endodontic pathogens (agar diffusion) and biofilm inhibition, evaluated both quantitatively (CFU/mL) and qualitatively via confocal laser scanning microscopy (CLSM) and SEM. Data were analyzed using ANOVA and Tukey’s test (α = 0.05). The modification of GelMA with antibiotic-laden fibrous microparticles increased the hydrogel swelling ratio and degradation rate. Cell viability was slightly reduced, although without any significant toxicity (cell viability > 50%). All hydrogels containing antibiotic-laden fibrous microparticles displayed antibiofilm effects, with the dentin substrate showing nearly complete elimination of viable bacteria. Altogether, our findings suggest that the engineered injectable antibiotic-laden fibrous microparticles hydrogels hold clinical prospects for endodontic infection ablation.

Visible light triggered controlled formation of rapidly self-healing hydrogels based on thiol-disulfide exchange.

The properties of stimuli-responsive hydrogels can be tailored under various external stimuli, but it is difficult to realize the customized adjustment of hydrogel properties since the crosslinking degree in the gelation process is intractable. Here, a visible light triggered thiol-disulfide exchange reaction was applied for constructing disulfide-crosslinked hydrogels from P(EMA-SS-PEG), a poly(ethylene glycol) grafted poly(ethyl methacrylate) derivative with a disulfide linkage as the grafting point. This photochemical method provides mild gelation conditions to handily regulate the morphology, mechanical properties, swelling ratio, and degradation rate of hydrogels by simply varying the irradiation time. Based on this strategy, these disulfide-crosslinked hydrogel coatings showed rapid self-healing in 10 min under ambient conditions, which was dependent on the width of the scratch, temperature, and humidity. Notably, spraying water on these coatings could significantly accelerate the self-healing process of large scratches (360 μm) at room temperature with a self-healing time of 1 hour, enabling the practical application of hydrogel coatings in a natural environment.

Hydrolytic (In)stability of Methacrylate Esters in Covalently Cross-Linked Hydrogels Based on Chondroitin Sulfate and Hyaluronic Acid Methacrylate.

Chondroitin sulfate (CS) and hyaluronic acid (HA) methacrylate (MA) hydrogels are under investigation for biomedical applications. Here, the hydrolytic (in)stability of the MA esters in these polysaccharides and hydrogels is investigated. Hydrogels made with glycidyl methacrylate-derivatized CS (CSGMA) or methacrylic anhydride (CSMA) degraded after 2–25 days in a cross-linking density-dependent manner (pH 7.4, 37 °C). HA methacrylate (HAMA) hydrogels were stable over 50 days under the same conditions. CS(G)MA hydrogel degradation rates increased with pH, due to hydroxide-driven ester hydrolysis. Desulfated chondroitin MA hydrogels also degrade, indicating that sulfate groups are not responsible for CS(G)MA’s hydrolytic sensitivity (pH 7.0–8.0, 37 °C). This sensitivity is likely because CS(G)MA’s N-acetyl-galactosamines do not form hydrogen bonds with adjacent glucuronic acid oxygens, whereas HAMA’s N-acetyl-glucosamines do. This bond absence allows CS(G)MA higher chain flexibility and hydration and could increase ester hydrolysis sensitivity in CS(G)MA networks. This report helps in biodegradable hydrogel development based on endogenous polysaccharides for clinical applications.

The effect of collagen hydrogels on chondrocyte behaviors through restricting the contraction of cell/hydrogel constructs.

Collagen is a promising material for tissue engineering, but the poor mechanical properties of collagen hydrogels, which tend to cause contraction under the action of cellular activity, make its application challengeable. In this study, the amino group of type I collagen (Col I) was modified with methacrylic anhydride (MA) and the photo-crosslinkable methacrylate anhydride modified type I collagen (CM) with three different degrees of substitution (DS) was prepared. The physical properties of CM and Col I hydrogels were tested, including micromorphology, mechanical properties and degradation properties. The results showed that the storage modulus and degradation rate of hydrogels could be adjusted by changing the DS of CM. In vitro, chondrocytes were seeded into these four groups of hydrogels and subjected to fluorescein diacetate/propidium iodide (FDA/PI) staining, cell counting kit-8 (CCK-8) test, histological staining and cartilage-related gene expression analysis. In vivo, these hydrogels encapsulating chondrocytes were implanted subcutaneously into nude mice, then histological staining and sulfated glycosaminoglycan (sGAG)/DNA assays were performed. The results demonstrated that contraction of hydrogels affected behaviors of chondrocytes, and CM hydrogels with suitable DS could resist contraction of hydrogels and promote the secretion of cartilage-specific matrix in vitro and in vivo.

Highly absorbent hydrogels comprised from interpenetrated networks of alginate\u2013polyurethane for biomedical applications

Developing new approaches to improve the swelling, degradation rate, and mechanical properties of alginate hydrogels without compromising their biocompatibility for biomedical applications represents a potential area of research. In this work, the generation of interpenetrated networks (IPN) comprised from alginate–polyurethane in an aqueous medium is proposed to design hydrogels with tailored properties for biomedical applications. Aqueous polyurethane (PU) dispersions can crosslink and interpenetrate alginate chains, forming amide bonds that allow the structure and water absorption capacity of these novel hydrogels to be regulated. In this sense, this work focuses on studying the relation of the PU concentration on the properties of these hydrogels. The results indicate that the crosslinking of the alginate with PU generates IPN hydrogels with a crystalline structure characterized by a homogeneous smooth surface with high capacity to absorb water, tailoring the degradation rate, thermal decomposition, and storage module, not altering the native biocompatibility of alginate, providing character to inhibit the growth of E. coli and increasing also its hemocompatibility. The IPN hydrogels that include 20 wt.% of PU exhibit a reticulation index of 46 ± 4%, swelling capacity of 545 ± 13% at 7 days of incubation at physiological pH, resistance to both acidic and neutral hydrolytic degradation, mechanical improvement of 91 ± 1%, and no cytotoxicity for monocytes and fibroblasts growing for up to 72 h of incubation. These results indicate that these novel hydrogels can be used for successful biomedical applications in the design of wound healing dressings.

Nanoindentation for Monitoring the Time-Variant Mechanical Strength of Drug-Loaded Collagen Hydrogel Regulated by Hydroxyapatite Nanoparticles.

Hydroxyapatite nanoparticle-complexed collagen (HAP/Col) hydrogels have been widely used in biomedical applications as a scaffold for controlled drug release (DR). The time-variant mechanical properties (Young’s modulus, E) of HAP/Col hydrogels are highly relevant to the precise and efficient control of DR. However, the correlation between the DR and the E of hydrogels remains unclear because of the lack of a nondestructive and continuous measuring system. To reveal the correlations, herein, we investigate the time-variant behavior of E for HAP/Col hydrogels during 28 days using the atomic force microscopy (AFM) nanoindentation technique. The initial E of hydrogels was controlled from 200 to 9000 Pa by the addition of HAPs. Subsequently, we analyzed the relationship between the DR of the hydrogels and the changes in their mechanical properties (ΔE) during hydrogel degradation. Interestingly, the higher the initial E value of HAP/Col hydrogels is, the higher is the rate of hydrogel degradation over time. However, the DR of hydrogels with higher initial E appeared to be significantly delayed by up to 40% at a maximum. The results indicate that adding an appropriate amount of HAPs into hydrogels plays a crucial role in determining the initial E and their degradation rate, which can contribute to the properties that prolong DR. Our findings may provide insights into designing hydrogels for biomedical applications such as bone regeneration and drug-delivery systems.

Berberine loaded chitosan nanoparticles encapsulated in polysaccharide-based hydrogel for the repair of spinal cord

The potential of berberine loaded in chitosan nanoparticles (BerNChs) within a hybrid of alginate (Alg) and chitosan (Ch) hydrogel was investigated for the substrate which is known as an inhibit activator proteins. The physicochemical properties of the developed Alg-Ch hydrogel were investigated by fourier-transform infrared spectroscopy. The swelling ability and degradation rate of hydrogels were also analyzed in a phosphate-buffered saline solution at physiological pH. The seeded scaffolds with endometrial stem cells as well as scaffolds alone were then transplanted into hemisected SCI rats. The SEM images displayed the favorable seeding and survival of the cells on the Alg-Ch/BerNChs hydrogel scaffold. The obtained data from immunostining of neuroflilament (NF), as a neuronal growth marker, in the various groups showed that the lowest and highest immunoractivity was belonged to the control and Alg-Ch/BerNCh seeded with ESCs groups, respectively. Finally, the Basso, Beattie, and Bresnahan (BBB) test confirmed the recovery of sensory and motor functions, clinically. The results suggested that combination therapy using the endometrial stem cells seeded on Alg-Ch/BerNChs hydrogel scaffold has the potential to regenerate the injured spinal cord and to limit the secondary damage.

Injectable chitosan-quince seed gum hydrogels encapsulated with curcumin loaded-halloysite nanotubes designed for tissue engineering application

The goal of tissue engineering is to assemble functional constructs that restore, maintain, or improve damaged tissues or organs. Hydrogels formed with natural polymers display high potential in artificial scaffolds for tissue repair as they can resemble the extracellular matrices. Thus, the aim of this study was to design nanocomposite hydrogels of chitosan/oxidized-modified quince seed gum/curcumin-loaded in halloysite nanotubes (CS/OX-QSG/CUR-HNTs) for tissue engineering applications. The produced hydrogels were analyzed for thermal stability, degradation, swelling ratio, gelling time and mechanical properties. The results showed that with increasing content of OX-QSG, thermal stability, swelling ratio, and degradation rate of hydrogels were improved. Notably, the optimal CS/OX-QSG hydrogel with ratio of 25:75 exhibited rapid gelation behavior (<50 s) and improved compressive strength (3.96 ± 0.64 MPa), representing the suitable hydrogel for application in tissue engineering. The MTT test showed that these hydrogels were non-toxic and any reduction or stop of NIH-3 T3 cells growth wasn't observed over time. In addition, CS/OX-QSG 25:75 hydrogels containing CUR-HNTs with 10 and 30% content was significantly (P < 0.05) enhanced cell growth and proliferation (around 150%). Obtained results illustrated that CS/OX-QSG hydrogels with ratio of 25:75 and the content of 30% CUR-HNTs can be an effective scaffold for application in tissue engineering.

Gelatin–Poly (γ-Glutamic Acid) Hydrogel as a Potential Adhesive for Repair of Intervertebral Disc Annulus Fibrosus

Study Design. An in vitro experimental study testing a Gelatin–poly (γ-glutamic acid) hydrogel for disc repair. Objective. To evaluate the cytocompatibility and degradability of the above mentioned hydrogel for intervertebral disc annular fibrosis (AF) repair. Summary of Background Data. No repair strategies for correcting annular defects in lumbar discectomy have been clinically well recognized. Exogenous supplementation of regenerative materials to fill defects is a minimally invasive way to restore compromised mechanical properties. The injected materials, most commonly gelatin-based materials with cross-linking agents, serve as sealants and as a scaffold for incorporating biomaterials for augmentation. However, cytotoxicity of hydrogel crosslinking agents is of concern in developing viable materials. Methods. This in vitro experimental study evaluated a newly developed gelatin-based hydrogel for intervertebral disc AF repair. Mechanical strength was augmented by γ-PGA, and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDC) was used for material crosslinking. Isolated bovine tail intervertebral discs (IVDs) were used to test the hydrogel, and hydrogel surface monolayer AF cell culture was used to investigate efficacy in hydrogel constructs of different EDC concentrations. Cell metabolic activity was evaluated with Alamar blue assay, cell viability assay with live/dead stain, and sulfated glycosaminoglycan (GAG) and double strain DNA were quantified to evaluate proliferation of implanted cells and synthesis of extracellular matrix (ECM) proteins. Results. EDC concentrations from 10 to 40 mM resulted in significant decreases in AF cell proliferation without obvious influence on cell viability. Higher EDC concentrations resulted in decreased percentage of Alamar blue reduction and GAG and DNA concentration, but did not affect GAG/DNA and live–dead ratios. Degradation tests revealed that higher EDC concentrations decreased the hydrogel degradation rate. Conclusion. The developed gelatin–poly (γ-PGA) hydrogel with 20 mM EDC concentration provides an effective gap-filling biomaterial with good cytocompatibility, suggesting substantial promise for use as a sealant for small AF defects. Level of Evidence: N/A

Recombinant human collagen/chitosan-based soft hydrogels as biomaterials for soft tissue engineering

Animal-derived collagen may contain viruses, and its impurity can cause immunological reactions. Chitosan, always required a neutralization step in fabricating it into the biocompatible tissue engineering scaffolds. To avoid these risks and simplify the production process, a series of recombinant human collagen/carboxylated chitosan (RHC-CHI) based soft hydrogel scaffolds were prepared by crosslinking-induced gelation and then investigated their feasibilities for use as soft tissue engineering scaffolds. The gelation time was optimized by modulating the biopolymer concentration or reaction temperature. The hydrogel swelling, degradation rate, and mechanical properties were also investigated. The results showed that these parameters could be tuned by adjusting either the RHC-to-chitosan ratio or the total polymer concentration. The mechanical properties of the hydrogels were improved by adding chitosan, but excess chitosan reduced the hydrogel mechanical strength and accelerated the degradation speed. Cytotoxicity tests showed that all fabricated soft hydrogels were biocompatible and displayed no cytotoxicity. Cytocompatibility tests and qRT-PCR studies indicated that the hydrogel system promoted the adhesion and proliferation of NIH-3T3 cells, and cellular activities were directly up-regulated by RHC. Finally, our in vivo study proved these hydrogels were able to accelerate the cell infiltration and wound closure. These results show that the soft RHC-CHI hydrogels show promise in soft-tissue engineering.

Tough and biodegradable polyurethane-curcumin composited hydrogel with antioxidant, antibacterial and antitumor properties

The functionalization of tough and biodegradable hydrogels is an important way to broaden their applications in biomedical field. However, most of the hydrophobic functional drugs are difficult to incorporate with the hydrogels. In this work, curcumin (Cur), a hydrophobic functional drug, was chosen to composite with polyurethane (PU) to obtain PU-Cur hydrogels by a direct and simple in-situ copolymerization. The incorporation of curcumin in PU hydrogel increases the crosslink but reduces the hydrophilicity and degradation rate of PU-Cur hydrogels. Thus, it can increase the mechanical strength to a maximum of 6.4±0.8 MPa and initial modulus to a maximum of 3.0±0.4 MPa. More importantly, curcumin incorporated in PU networks is not deactivated. The degradation products of PU-Curs at relatively low concentrations (2.5 mg/mL) can scavenge free radicals very efficiently (maximum over 90%), which exhibits strong antioxidant properties to improve wound healing. Moreover, based on the photochemical activity of curcumin, notable inhibition effects of the degradation products of PU-Curs against bacteria (maximum over 80%) and cancer cells are demonstrated with blue light treatment as a photodynamic therapy (PDT). Therefore, the beneficial effects of curcumin are retained in PU-Cur hydrogels, suggesting potential use as wound dressings or tumor isolation membranes. This work proposes a promising strategy to combine hydrophobic functional drugs with hydrophilic hydrogels for applications in a wide range of biomaterials.

Osteogenic Effect of a Biodegradable BMP-2 Hydrogel Injected into a Cannulated Mg Screw.

Cannulated screws, containing an internal hole for inserting a guide pin, are commonly used in the management of bone fractures. Cannulated Mg screws can be biodegraded easily because their increased surface area including that of the inner hole rapidly reacts with body fluids. To delay biodegradation of cannulated Mg screws and improve bone regeneration, we developed a specific type of screw by injecting it with gelatin hydrogels [10 wt % gelatin(gel) with 0.09 v/v % glutaraldehyde (cross-linker)] containing different concentrations (5, 10, or 25 μg/mL) of bone morphogenic proteins (BMPs). We analyzed the properties and biocompatibility of the screws with and without BMP-2 and found that the release rate of BMP-2 in the hydrogel changed proportionately with the degradation rate of the cross-linked hydrogel. Loading BMP-2 in the hydrogel resulted in sustained release of BMP-2 for 25 to 40 days or more. The degradation rate of BMP-2 hydrogels was inversely proportional to the concentration of BMP-2. The injection of the hydrogels in the cannulated screw delayed biodegradation inside of the screw by simulated body fluid. It also induced uniform corrosion and the precipitation of bioactive compounds onto the surface of the screw. In addition, osteoblast proliferation was very active near the BMP-2 hydrogels, depending on the BMP-2 concentration. The BMP-2 in the hydrogel improved cell differentiation. The cannulated screw injected with 10 μL/mL BMP-2 hydrogel prevented implant biodegradation and enhanced osteoconduction and osteointegration inside and outside the screw. In addition, the properties of BMP-2-loaded hydrogels can be changed by controlling the amount of the cross-linker and protein, which could be useful for tissue regeneration in other fields.

Chemical cross-linking on gelatin-hyaluronan loaded with hinokitiol for the preparation of guided tissue regeneration hydrogel membranes with antibacterial and biocompatible properties

The mechanical properties and structural stability of hydrogels and their performance in antidegradation can be enhanced by cross-linking them with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC). However, residual EDC compromises the biocompatibility of cross-linked hydrogels and the formability of un-cross-linked hydrogels. In this study, a facile process for preparing hydrogel regenerative membranes exerting antibacterial effects and containing gelatin/hyaluronic acid (G/HA) through solution casting was proposed. The membranes were cross-linked with EDC (G/HA-Ec-0H) and impregnated with two concentrations of the antibacterial agent of hinokitiol (G/HA-Ec-2H and G/HA-Ec-4H). Amide bonds formed, and the rate of active amino acid fixation was higher than 90%, which was directly proportional to the degree of cross-linking. The G/HA-Ec-2H and G/HA-Ec-4H groups with hinokitiol showed good antibacterial properties. The rate of hydrogel degradation decreased, and the integrity of sample morphology was maintained at more than 80% for over 3 days in the immersion. Then, the hydrogel structures relaxed and disintegrated through a rapid degradation reaction within 24 h. The biocompatibility results showed that low concentrations of hinokitiol did not affect cell viability. Moreover, hydrogel membranes after 14 days of cell incubation showed good cell adhesion and proliferation. In summary, the membrane biostability of the cross-linked gelatin/hyaluronan hydrogels was enhanced by EDC at a biocompatible concentration, and the functionalized group of G/HA-Ec-2H shows potential as a biodegradable material for biocompatible tissue-guarded regeneration membranes with antibacterial properties.

Doubly crosslinked biodegradable hydrogels based on gellan gum and chitosan for drug delivery and wound dressing

Biopolymer-based hydrogels with sustained drug release capability and antibacterial activity have exhibited great potential in clinical application in drug delivery and wound healing. In this study, a new type of composite wound dressing hydrogel aiming at avoiding wound infection was developed through embedding drug loaded gellan gum microspheres (GMs) into a doubly crosslinked hydrogel, which was constructed by Schiff-base crosslinking of oxidized gellan gum (OG) (pre-crosslinked by calcium ion) and carboxymethyl chitosan (CMCS). The gelation time, swelling index, degradation rate and mechanical properties of the blank hydrogel was optimized by varying the ratios of CMCS/OG (w/w) with fixed OG/calcium (w/w) ratio. The best overall performance of the hydrogel was obtained when CMCS/OG is 16/7 (w/w), with a 139 s gelation time, swelling index remained above 30 after swelling equilibrium, 100.5% degradation rate on the seventh day, and 8.8 KPa compressive modulus. After being embedded with cargo-loaded GMs, the aforementioned performance of the blank hydrogel was improved, and the sustained release of cargoes (antibacterial drugs, tetracycline hydrochloride and silver sulfadiazine) was observed. Moreover, the excellent antibacterial activity of the composite hydrogel was also demonstrated in vitro. These results support the bioactive composite hydrogel can be employed as a promising injectable scaffold for promoting wound regeneration and drug delivery.

One-pot synthesis of dibenzaldehyde-terminated poly(ethylene glycol) for preparation of dynamic chitosan-based amphiphilic hydrogels

In order to synthesize dynamic amphiphilic hydrogels, in the first step, dibenzaldehyde-terminated telechelic poly(ethylene glycol) (PEG-DA) was synthesized via simple one-pot method by using hexamethylene diisocyanate and para-hydroxybenzaldehyde. In the second step, 4-arm star-shaped polycaprolactone tetraaldehyde (4sPCL-TA) was synthesized in three steps. All of the synthesized prepolymers and functionalization reactions were characterized by 1H-NMR and FT-IR spectroscopy. Finally, a series of new dynamic amphiphilic hydrogels were prepared through dynamic covalent Schiff-base linkages by simply mixing nontoxic chitosan, PEG-DA and 4sPCL-TA solutions. The chemical structure, morphology, thermal properties, gel degradation, mechanical performance, swelling behavior and self-healing capability of hydrogels were investigated. The obtained results showed that the hydrogels present suitable self-healing performance without any external stimulus. These properties of hydrogels can be attributed to covalent Schiff base linkages between the aldehyde and amine groups of prepolymers. Moreover, the hydrogels displayed pH-dependent degradation behavior. Swelling degree and degradation rate of hydrogels decreased with introducing of 4sPCL-TA in hydrogel networks. In addition, the thermal and mechanical properties of hydrogels were improved with incorporation of 4sPCL-TA into the network structure.

Controlled release of basic fibroblast growth factor from a peptide biomaterial for bone regeneration.

Self-assembled peptide scaffolds based on D-RADA16 are an important matrix for controlled drug release and three-dimensional cell culture. In this work, D-RADA16 peptide hydrogels were coated on artificial bone composed of nano-hydroxyapatite/polyamide 66 (nHA/PA66) to obtain a porous drug-releasing structure for treating bone defects. The developed materials were characterized via transmission electron microscopy and scanning electron microscopy. The proliferation and adhesion of bone mesenchymal stem cells (BMSCs) were examined by confocal laser microscopy and CCK-8 experiments. The osteogenic ability of the porous materials towards bone BMSCs was examined in vitro by staining with Alizarin Red S and alkaline phosphatase, and bioactivity was evaluated in vivo. The results revealed that nHA/PA66/D-RADA16/bFGF reduces the degradation rate of D-RADA16 hydrogels and prolongs sustained release of bFGF, which would promote BMSCs proliferation, adhesion and osteogenesis in vitro and bone repair in vivo. Thus, it deserves more attention and is worthy of further research.

Dual Functional Lysozyme-Chitosan Conjugate for Tunable Degradation and Antibacterial Activity.

Hydrogels with controlled degradation and sustained bactericidal activities are promising biomaterial substrates to repair or regenerate the injured tissue. In this work, we present a unique pair of lysozyme and chitosan as a hydrogel that can promote cell growth and proliferation while concomitantly preventing infection during the gradual process of hydrogel degradation and tissue ingrowth. Lysozyme and chitosan containing cell adhesion motifs are chemically modified with photoreactive methacrylate moieties to obtain a crosslinked hydrogel network by visible light irradiation. The resulting lysozyme-chitosan conjugate successfully modulates the degradation rate of hydrogels while promoting cell adhesion, proliferation, and matrix formation with no cytotoxicity. The hydrogel also exerts an intrinsic antibacterial effect by combining antimicrobial features of chitosan and lysozyme. This work demonstrates an advanced hydrogel platform with dual function of tunable degradation and infection control for tissue engineering and wound healing applications.

Photolabile Linkers: Exploiting Labile Bond Chemistry to Control Mode and Rate of Hydrogel Degradation and Protein Release.

Photolabile moieties have been utilized in applications ranging from peptide synthesis and controlled protein activation to tunable and dynamic materials. The photochromic properties of nitrobenzyl (NB) based linkers are readily tuned to respond to cytocompatible light doses and are widely utilized in cell culture and otherbiological applications. While widely utilized, little is known about how the microenvironment, particularly confined aqueous environments (e.g., hydrogels), affects both the mode and rate of cleavage of NB moieties, leading to unpredictable limitations in control over system properties (e.g., rapid hydrolysis or slow photolysis). To address these challenges, we synthesized and characterized the photolysis and hydrolysis of NB moieties containing different labile bonds (i.e., ester, amide, carbonate, or carbamate) that served as labile crosslinkswithin step-growth hydrogels. We observed that NB ester bond exhibited significant rates of both photolysis and hydrolysis, whereas, importantly, the NB carbamate bond had superior light responsiveness and resistance to hydrolysis within the hydrogel microenvironment. Exploiting this synergy and orthogonality of photolytic and hydrolytic degradation, we designed concentric cylinder hydrogels loaded with different cargoes (e.g., model protein with different fluorophores) for either combinatorial or sequential release, respectively. Overall, this work provides new facile chemical approaches for tuning the degradability of NB linkers and an innovative strategy for the construction of multimodal degradable hydrogels, which can be utilized to guide the design of not only tunable materials platforms but also controlled synthetic protocols or surface modification strategies.