Hydrogel Drug Research Articles

Construction of an intelligent pH-sensitive hydrogel drug delivery system and its application in gastric ulcer treatment

The occurrence of gastric ulcer is mainly due to the damage of gastric mucosa which leads to inward flow of gastric acid to corrode the gastric cavity, thus producing gastric fever, vomiting, loss of appetite and other adverse reactions. Prevention and treatment of such injuries are crucial. In this study, a simple and non-toxic composite hydrogel (PLGA/CMCS) was prepared through Schiff base reaction between poly(lactic-co-glycolic acid) (PLGA) and carboxymethyl cellulose (CMCS). Subsequently, compound 1 was loaded onto it to construct PLGA/CMCS@1. A series of structural characterization and performance experiments were conducted on these novel hydrogel polymers. Furthermore, we detected the gene expression level of Fas/FasL apoptotic pathway after treating the cells with different concentrations of PLGA/CMCS@1 through an ethanol-induced damaged gastric mucosal epithelial cell model. The results showed that the system was able to significantly regulate the expression of genes related to the apoptotic pathway. The system can regulate the Fas/FasL apoptosis pathway to treat gastric ulcer.

Responsive Hydrogel-Based Drug Delivery Platform for Osteoarthritis Treatment

Osteoarthritis (OA) is the most prevalent chronic joint disorder and is a major cause of disability among the elderly population. The degeneration and damage of articular cartilage associated with OA can result in a diminished range of motion in joints, subsequently impacting fundamental activities such as ambulation, standing, and grasping objects. In severe cases, it may culminate in disability. Traditional pharmacological treatments are often accompanied by various side effects, while invasive surgical procedures increase the risk of infection and thrombosis. Consequently, identifying alternative new methods for OA treatment remains a formidable challenge. With advancements in responsive hydrogel drug delivery platforms, an increasing number of strategies have emerged to enhance OA treatment protocols. Injectable response hydrogel drug delivery platforms show many advantages in treating OA, including improved biocompatibility, prolonged drug release duration, elevated drug loading capacity and enhanced sensitivity. This article reviews the recent progress of injectable responsive hydrogel drug delivery platform for OA treatment over the past few years. These innovative methodologies present new strategies and directions for future OA treatment while summarizing a series of challenges faced during the clinical transformation of injectable response hydrogel drug delivery platforms. Overall, injectable responsive hydrogel drug delivery platforms show great potential in treating OA, especially regarding improving drug retention time and stimulus-responsive release at the lesion sites. These innovative methods provide new hope for future OA treatment and point the way for clinical applications.

Adhesive lipophilic gels delivering rapamycin prevent oral leukoplakia from malignant transformation

Oral leukoplakia (OLK) is the most emblematic oral potentially malignant disorder that may precede the diagnosis of oral squamous cell carcinoma (OSCC) and has an overall malignant transformation rate of 9.8 %. Early intervention is crucial to reduce the malignant transformation rate from OLK to OSCC but the lack of effective local pharmaceutical preparations poses a challenge to clinical management. Rapamycin is speculated to prevent OLK from carcinogenesis and its inherent lipophilicity facilitates its penetration into stratum corneum. Nevertheless, hydrophilic hydrogels frequently encounter challenges when attempting to deliver lipophilic drugs. Furthermore, the oral cavity presents a complex environment defined by oral motor functions, saliva secretion cycles, dynamic fluctuations, and protective barriers comprising mucus and lipid layers. Consequently, addressing issues of muco-penetration and muco-adhesion is imperative for developing an effective drug delivery system aiming at delivering rapamycin to target oral potentially malignant disorders.Here, a dual-function hydrogel drug delivery system integrating adhesion and lipophilicity was successfully developed based on polyvinyl alcohol (PVA) and dioleoyl phosphatidylglycerol (DOPG) via dynamic boronic ester bonds. Rheological experiments based on orthogonal design revealed that PVA-DOPG hydrogels exhibited ideal adhesive strength (around 6 kPa) and could adhere to various surfaces in both dry and wet conditions. PVA-DOPG hydrogels also significantly promoted lipophilic molecules’ penetration into stratum corneum (integrated fluorescence density of 6.95 ± 0.52 × 106 and mean fluorescence depth of 0.96 ± 0.07 mm) of ex-vivo porcine buccal mucosa (p < 0.001). Furthermore, PVA-DOPG hydrogels incorporating rapamycin inhibited malignant transformation of OLK mouse model induced by 4-Nitroquinoline N-oxide (4-NQO), distinct improvements in survival (the neoplasm incidence density at the 40th day is 0.0091) (p < 0.05), decrease in neoplasm incidence density of 36.36 % and inhibition rate in neoplasm volume of 75.04 ± 33.67 % have been demonstrated, suggesting the hydrogels were valuable candidates for potential applications in the management of OLK.

Hydrogel-based formulations for urothelial cancer therapy.

Drug infusion therapy after surgery for urothelial carcinoma is an effective measure to reduce cancer recurrence rate. Hydrogels are drug carriers with good biocompatibility and high drug loading capacity, which can optimize the pharmacokinetics of drugs in the urinary system to improve the therapeutic effect. Compared with the traditional free drug in situ perfusion, the hydrogel drug loading system can still maintain effective drug concentration in the face of continuous urinary flushing due to its good mucosal adhesion effect. The significantly prolonged drug retention time can not only improve the therapeutic effect of drugs, but also reduce the discomfort and risk of urinary tract infections caused by frequent drug infusion, and improve patient compliance. In addition, the combination of hydrogel with nanoparticles and magnetic materials can also improve the mucosal permeability and targeting effect of the hydrogel drug loading system, so as to overcome the mucus layer of urinary epithelium and the physiological barrier of tumor and minimize the impact on normal tissue and cell functions. At present, the research of hydrogels for urothelial cancer treatment involves chemotherapy, immunotherapy, gene therapy, inhibition of metabolism and multi strategy synergistic therapy. This review summarizes the research progress of hydrogels for the treatment of urothelial carcinoma, hoping to provide a reference for the future research of safe, reliable, effective, and advanced hydrogels with little side effects.

Hydrogel and Microgel Collaboration for Spatiotemporal Delivery of Biofactors to Awaken Nucleus Pulposus‐Derived Stem Cells for Endogenous Repair of Disc

AbstractDepletion of nucleus pulposus‐derived stem cells (NPSCs) is a major contributing factor to the attenuation of endogenous regenerative capacity in intervertebral disc degeneration (IVDD). Introducing a hydrogel drug delivery system is a potential strategy for counteracting endogenous cell depletion. The present study proposes a delivery platform for the spatiotemporal release of multiple drugs by combining sodium alginate hydrogels with gelatin microgels (SCGP hydrogels). The SCGP hydrogels facilitated the initial release of chondroitin sulfate (ChS) and the gradual release of an independently developed parathyroid hormone‐related peptide (P2). The combined action of these two small molecule drugs “awakened” the reserve NPSCs, mitigated cell damage induced by H2O2, significantly enhanced their biological activity, and promoted their differentiation toward nucleus pulposus cells. The mechanical and viscoelastic properties of the hydrogel are enhanced by physical and chemical dual cross‐linking to adapt to the loading environment of the degenerated disc. A rat IVDD model is used to validate that the SCGP hydrogel can significantly inhibit the progression of IVDD and stimulate the endogenous repair of IVDD. Therefore, the spatiotemporal differential drug delivery system of the SCGP hydrogel holds promise as a convenient and efficacious therapeutic strategy for minimally invasive IVDD treatment.

Synthesis and characterization of a novel dual sensitive iron nanoparticles incorporated Schiff base composite hydrogel for diabetic wound healing therapy

Chronic wounds in diabetic patients deteriorate into multiple infections. A multifunctional transdermal material with high self-healing ability, remodeling capability, antibacterial and radicle scavenging activity, and an excellent multi-sensitive carrier was needed to promote wound healing. For that, Oxidized Cellulose (OC) and gelatin (GLN) are selected to construct a dual drug-loaded Schiff base hydrogel with iron nanoparticle (IONPS) incorporation for the controlled and sustained release of Insulin (INS) and Metfomin (MET), which synergistically promote wound repair. The INS/MET-IONPS-OC/GLN hydrogel drug payload was characterized using FT-IR, XRD, DLS, ZETA, TG, FE-SEM, TEM, and VSM analysis. The high drug loading and encapsulation efficiency were 93.20 % and 98.8 % for INS and 90.2 % and 95.1 % for MET, respectively. The temperature-sensitive drug release (92.0 % of INS and 90.0 % of MET) percentage is much better than the pH-sensitive drug release (83.5 % of INS and 80.2 % of MET). Above 90.0 % viability in MTT and apoptosis assay reveals the nontoxic nature of the INS/MET-IONPS-OC/GLN towards L929 normal cell lines. The zone of inhibition value of 12 and 15 mm in gram-negative bacteria reveals the anti-bacterial effect. The antioxidant activity of the carrier shields the cells against reactive oxygen species promotes healing rate ensures by DPPH assay.The cell proliferation and angiogenesis were confirmed by scratch assay on L929 cell lines in diabetic and non-diabetic conditions, showing the healing ability of the INS/MET-IONPS-OC/GLN hydrogel.

Versatile hydrogel drug carrier loading with peptide-carbon dots conjugates for efficient targeting and synergistic suppression of breast cancer cell

Breast cancer become the most prevalent malignancy and is rising up to the first leading cause of cancer-related mortality among the female people globally. Approaches for safe, specific targeting and efficient inhibition of breast cancer cells, are urgently demanded for lifting the survival rate of breast tumor-bearing patients. Herein, a versatile hydrogel drug carrier consisting of doxorubicin (DOX)-loaded hydrogel microsphere and carbon dots (CDs)-loaded peptide nanowires (DOX@PEG/PNFs-CDs) was constructed, presenting specific targeting and synergistic anti-cancer cell potencies. The hydrogel PEG microspheres with a rich porous structure benefited the drug loading efficiency, demonstrating good biodegradability and higher drug release efficiency at acidic environment. Benefiting from the RGD group of the peptide nanowires, the drug-loaded system specific targeted onto the MDA-MB-231 cells, subsequently promoting the synergistic inhibition of the cancer cell growth by DOX and metformin derived CDs. This all-in-one smart drug carrier post a promising strategy for breast cancer treatment.

Advancing Ovarian Cancer Therapeutics: The Role of Targeted Drug Delivery Systems.

Ovarian cancer (OC) is the most lethal reproductive system cancer and a leading cause of cancer-related death. The high mortality rate and poor prognosis of OC are primarily due to its tendency for extensive abdominal metastasis, late diagnosis in advanced stages, an immunosuppressive tumor microenvironment, significant adverse reactions to first-line chemotherapy, and the development of chemoresistance. Current adjuvant chemotherapies face challenges such as poor targeting, low efficacy, and significant side effects. Targeted drug delivery systems (TDDSs) are designed to deliver drugs precisely to the tumor site to enhance efficacy and minimize side effects. This review highlights recent advancements in the use of TDDSs for OC therapies, including drug conjugate delivery systems, nanoparticle drug delivery systems, and hydrogel drug delivery systems. The focus is on employing TDDS to conduct direct, effective, and safer interventions in OC through methods such as targeted tumor recognition and controlled drug release, either independently or in combination. This review also discusses the prospects and challenges for further development of TDDSs. Undoubtedly, the use of TDDSs shows promise in the battle against OCs.

Fungal Enzyme-Responsive Hydrogel Drug Delivery Platform for Triggered Antifungal Release.

Fungal infections can lead to debilitating consequences if they are not treated effectively. Antifungal drugs used to treat these infections can be toxic and overuse contributes to growing antifungal resistance. Candida spp., particularly C. albicans, are implicated in a majority of these infections. Virulent C. albicans produce secreted aspartic proteases (Saps) that aid in pathogen tissue invasion and proliferation at an infected site. Here, fungi-responsive hydrogels are developed that degrade in the presence of Saps to provide a triggered release of encapsulated liposomal antifungals. The hydrogel backbone incorporates a Sap-cleavable peptide sequence enabling Sap-responsive degradation. Hydrogels are found to effectively degrade in the presence of Saps extracted from C. albicans. Encapsulated liposomal antifungals show similar release kinetics as hydrogel degradation products in the presence of Saps, supporting a degradation-dependent release mechanism. Antifungal liposome-loaded responsive hydrogels exhibit successful eradication of C. albicans cultures and remain stable in sterile murine wound fluid. Finally, no significant cytotoxicity is observed for murine fibroblast cells and red blood cells exposed to hydrogel degradation products. These fungi-responsive hydrogels have the potential to be used for local, on-demand delivery of antifungal drugs, for effective treatment of fungal infections while helping to limit unnecessary exposure to thesetherapeutics.

Facile fabrication of a thermal/pH responsive IPN hydrogel drug carrier based on cellulose and chitosan through simultaneous dual-click strategy

Herein, an interpenetrating network hydrogel (IPN-Gel) based on cellulose and chitosan was synthesized via simultaneous amino-anhydride and azide–alkyne click reaction in water in one pot. The samples were characterized by various analytical methods including FTIR, SEM, XRD, XPS, 1H NMR and so forth. The fabrication conditions were optimized by single factor experiments with water uptake (WU) and gel mass fraction (GMF) as two indexes. The WU and GMF of the IPN-Gel prepared under optimized conditions were 1192.37 % and 74.00 %, respectively. Its WU descended with the ascension in temperature, and first descended and then gradually ascended with the ascension in pH, confirming that the IPN-Gel had thermal/pH dual responsiveness. Using 5-Fu as a model drug, the release behavior of 5-Fu in IPN-Gel was explored. Its release behavior could be regulated by changing temperature and pH values, and it followed the Korsmeyer Peppas model. The viability of 4 T1 cells and HUVEC cells exceeded 80 % after 48 h of incubation at a high concentration of 200 μg/mL IPN-Gel, and hemolytic percentage was below the allowed limit of 5 %. The study provides a new strategy for the preparation of the IPN-Gel with biocompatibility, swelling reversibility and controllable drug release.

A wearable iontophoresis enables dual-responsive transdermal delivery for atopic dermatitis treatment

Atopic dermatitis is a chronic, inflammation skin disease that remains a major public health challenge. The current drug-loading hydrogel dressings offer numerous benefits with enhanced loading capacity and a moist-rich environment. However, their development is still limited by the accessibility of a suitable driven source outside the clinical environment for precise control over transdermal delivery kinetics. Here, we prepare a sulfonated poly(3,4-ethylenedioxythiophene) (PEDOT) polyelectrolyte hydrogel drug reservoir that responds to different stimuli-both endogenous cue (body temperature) and exogenous cue (electrical stimulation), for wearable on-demand transdermal delivery with enhanced efficacy. Functioned as both the drug reservoir and cathode in a Zn battery-powered iontophoresis patch, this dual-responsive hydrogel achieves high drug release efficiency (68.4 %) at 37 °C. Evaluation in hairless mouse skin demonstrates the efficacy of this technology by facilitating transdermal transport of 12.2 μg cm−2 dexamethasone phosphate when discharged with a 103 Ω external resistor for 3 h. The Zn battery-driven iontophoresis results in an effective treatment of atopic dermatitis, displaying reductions in epidermal thickness, mast cell infiltration inhibition, and a decrease in IgE levels. This work provides a new treatment modality for chronic epidermal diseases that require precise drug delivery in a non-invasive way.

Preparation of TiO2 nanotube array/black phosphorus hydrogel drug slow release system based on reactive oxygen response

Black phosphorus quantum dots (BPQDs) were prepared by liquid stripping method, combined with a gel with reactive oxygen species (ROS) decomposition property, and wrapped onto TiO2 nanotube arrays loaded with ibuprofen (IBU) to construct a drug delivery system with near-infrared light (NIR) stimulation response. The generated ROS due to the presence of BPQDs can not only break the dynamic covalent bonds in the gel structure, leading to the decomposition of the gel, achieving NIR-responsive release of IBU and accelerating the release rate of IBU, but at the same time, ROS can play an obvious antibacterial role.

Vancomycin-encapsulated hydrogel loaded microarc-oxidized 3D-printed porous Ti6Al4V implant for infected bone defects: Reconstruction, anti-infection, and osseointegration

Infected bone defect is a formidable clinical challenge. Conventional approaches to prevention and treatment for infected bone defects are unsatisfactory. The key elements of the treatment are bone defect reconstruction, anti-infection, and osteogenesis. Conventional treatment methods remain unsatisfactory owing to the absence of composite integrating materials with anti-infective, and osteogenic activities as well as proper mechanical strength at the same time. In this study, we fabricated a vancomycin-encapsulated hydrogel with bacteria-responsive release properties combined with a shaved porous (submicron-micron) three-dimensional-printed Ti6Al4V implant. The implant surface, modified with submicron-sized pores through microarc oxidation (MAO), showed enhanced osteogenic activity and integrated well with the hydrogel drug release system, enabling sustained vancomycin release. In vitro experiments underscored the commendable antibacterial ability, biosafety, and osteoinductive potential. Effective antibacterial and osteogenic abilities of the implant were further demonstrated in vivo in infected rabbit bone defects. These results showed that the vancomycin-encapsulated hydrogel-loaded microarc-oxidized 3D-printed porous Ti6Al4V can repair the infected bone defects with satisfactory anti-infection and osseointegration effects.

Hydrogels for Nucleic Acid Drugs Delivery.

Nucleic acid drugs are one of the hot spots in the field of biomedicine in recent years, and play a crucial role in the treatment of many diseases. However, its low stability and difficulty in target drug delivery are the bottlenecks restricting its application. Hydrogels are proven to be promising for improving the stability of nucleic acid drugs, reducing the adverse effects of rapid degradation, sudden release, and unnecessary diffusion of nucleic acid drugs. In this review, the strategies of loading nucleic acid drugs in hydrogels are summarized for various biomedical research, and classify the mechanism principles of these strategies, including electrostatic binding, hydrogen bond based binding, hydrophobic binding, covalent bond based binding and indirect binding using various carriers. In addition, this review also describes the release strategies of nucleic acid drugs, including photostimulation-based release, enzyme-responsive release, pH-responsive release, and temperature-responsive release. Finally, the applications and future research directions of hydrogels for delivering nucleic acid drugs in the field of medicine are discussed.

A review of recent advances in drug loading, mathematical modeling and applications of hydrogel drug delivery systems

A review of recent advances in drug loading, mathematical modeling and applications of hydrogel drug delivery systems

Topical application of daphnetin hydrogel for traumatic brain injury.

Traumatic brain injury (TBI) causes neuronal cell damage and dysfunction. According to previous studies, daphnetin (Dap) has a protective effect in neurological injury. However, the in vivo bioavailability of daphnetin is not high. The purpose of this study was to determine whether administering daphnetin directly into the site of injury via a hydrogel drug carrier could improve its therapeutic impact. Tripolycerol monostearates / daphnetin (TM/Dap) hydrogels were prepared and characterised using water bath heating, scanning electron microscopy (SEM) and small animal in vivo imaging techniques. The TBI model was established using the Feeney free fall impact method. Using the Morris water maze test, the mNSS neurological deficit rating scale, haematoxylin-eosin staining, and liver and kidney function tests, the therapeutic benefit of TM/Dap and its toxic side effects were assessed. The therapeutic effects of TM/Dap were further investigated using wet and dry gravimetric methods, Evans blue staining, protein immunoblotting, immunofluorescence staining techniques and ELISA. The efficacy of the TM/Dap hydrogel in gradually releasing daphnetin in the context of traumatic brain damage was shown by both in vitro and in vivo tests. Behavioral experiments showed that the learning and spatial memory abilities of TM/Dap hydrogel treated mice were significantly improved in the water maze experiment. And TM/Dap hydrogel has high biosafety for organisms. The results of the therapeutic mechanism of action showed that TM/Dap hydrogel showed more significant efficacy in reducing the neuroinflammatory response caused by TNF-α, IL-6 and other factors, as well as promoting the recovery of post-traumatic neurological function. The use of hydrogel as a drug carrier for daphnetin showed more significant efficacy in reducing neuroinflammatory response, protecting nerve tissue and promoting post-traumatic neurological recovery compared with traditional drug delivery methods.

Drug Release Study of Polyvinyl Alcohol-Gelatin-Montmorillonite Bionanocomposite Hydrogel Drug Delivery Systems Loaded with Clindamycin

One of the challenges facing medical science is the proper formulation of drug delivery systems for the correct transfer of active pharmaceutical ingredients to the body. Polymer and nanocomposite hydrogels have been considered ideal options in the preparation of drug delivery systems due to their proper properties, such as hydrophilicity and biocompatibility. In this, our research, described in this manuscript, the drug release from polyvinyl alcohol (PVA)-gelatin-montmorillonite (MMT) bionanocomposite hydrogel drug delivery systems loaded with clindamycin was studied. The structural and physical properties of prepared nanocomposite hydrogels were investigated using X-ray diffractometry (XRD), field emission scanning electron microscopy (FESEM), Fourier-transform infrared spectroscopy (FTIR), Brunauer-Emmette-Teller (BET) analysis, gel fraction and swelling tests. The results showed that by adding MMT clay to PVA-gelatin hydrogels, the amount of gel fraction increased, and due to the decrease in the size of the pores, the amount of swelling decreased. The results of the drug release tests showed that the release rate of clindamycin was inversely related to the percentage of MMT added to the nanocomposite hydrogel. The results also showed that the shape of the drug delivery system and its dimensions affected the release rate of clindamycin. The dominant mechanism of drug release in all samples was found to be Fickian transport. Considering the favorable in-vitro drug release performance of our PVA-gelatin-MMT nanocomposite hydrogels in the release of clindamycin, it was concluded that they are suitable options for preparing practical drug delivery systems with controlled drug release ability.

Corn-inspired high-density plasmonic metal-organic frameworks microneedles for enhanced SERS detection of acetaminophen

Effective monitoring of acetaminophen (APAP) dosage is crucial for preventing antipyretic abuse, ensuring therapeutic efficacy, and minimizing toxic effects. However, existing self-monitoring methods are limited. In this study, we designed a plasmonic microneedle (MN) sensor for real-time nondestructive monitoring of acetaminophen levels in dermal interstitial fluid (ISF) by employing a handheld Raman spectrometer. The fabricated MN sensor incorporated a high-density plasmonic MOFs known as HDPM, which unique structure of large specific surface area, specific pore structure as well as high density gold nanospheres packing enabled the excellent performance of selective ISF drug enrichment and surface-enhanced Raman scattering (SERS). The maximum electric field enhancement factor of the HDPM nanostructure could be calculated as 5.73 × 107. The developed HDPM@MNs was characterized with a core-shell type “soft on the outside and rigid on the inside” structure, which exhibited sufficient hardness and flexibility to penetrate the dermal tissue with little damage, and robust SERS enhancement effect in APAP detection without any interfering peaks. Through a hydrogel drug simulation experiment, the sensor demonstrated robust capabilities for acetaminophen enrichment and monitoring, exhibiting excellent stability and repeatability. The quantitative detection window spanned from 1 to 100 μM, with a low detection limit reaching 0.45 μM. Furthermore, by monitoring the concentration of acetaminophen in the interstitial fluid of rat skin at different doses and for different administration times, the HDPM@MNs can be used to determine the pharmacokinetics of acetaminophen in rats and the physiological characteristics associated with various dosage regimens. This work not only holds promise for drug monitoring but also provides a novel approach for nondestructive monitoring of other crucial low-abundance physiological markers.

Wrecking neutrophil extracellular traps and antagonizing cancer-associated neurotransmitters by interpenetrating network hydrogels prevent postsurgical cancer relapse and metastases

Tumor-promoting niche after incomplete surgery resection (SR) can lead to more aggressive local progression and distant metastasis with augmented angiogenesis-immunosuppressive tumor microenvironment (TME). Herein, elevated neutrophil extracellular traps (NETs) and cancer-associated neurotransmitters (CANTs, e.g., catecholamines) are firstly identified as two of the dominant inducements. Further, an injectable fibrin-alginate hydrogel with high tissue adhesion has been constructed to specifically co-deliver NETs inhibitor (DNase I)-encapsulated PLGA nanoparticles and an unselective β-adrenergic receptor blocker (propranolol). The two components (i.e., fibrin and alginate) can respond to two triggers (thrombin and Ca2+, respectively) in postoperative bleeding to gelate, shaping into an interpenetrating network (IPN) featuring high strength. The continuous release of DNase I and PR can wreck NETs and antagonize catecholamines to decrease microvessel density, blockade myeloid-derived suppressor cells, secrete various proinflammatory cytokines, potentiate natural killer cell function and hamper cytotoxic T cell exhaustion. The reprogrammed TME significantly suppress locally residual and distant tumors, induce strong immune memory effects and thus inhibit lung metastasis. Thus, targetedly degrading NETs and blocking CANTs enabled by this in-situ IPN-based hydrogel drug depot provides a simple and efficient approach against SR-induced cancer recurrence and metastasis.

Impact of Peptide Length and Solution Conditions on Tetrameric Coiled Coil Formation.

Unlike naturally derived peptides, computationally designed sequences offer programmed self-assembly and charge display. Herein, new tetrameric, coiled coil-forming peptides were computationally designed ranging from 8 to 29 amino acids in length. Experimental investigations revealed that only the sequences having three or more heptads (i.e., 21 or more amino acids) exhibited coiled coil behavior. The shortest stable coiled coil sequence had a melting temperature (Tm) of approximately 58 ± 1 °C, making it ideal for thermoreversible assembly over moderate temperatures. Effects of pH and monovalent salt were examined, revealing structural stability over a pH range of 4 to 11 and an enhancement in Tm with the addition of salt. The incorporation of the coiled coil as a hydrogel cross-linker results in a thermally and mechanically reversible hydrogel. A subsequent demonstration of the hydrogel printed through a syringe illustrated one of many potential uses from 3D printing to injectable hydrogel drug delivery.