Hydrogel-based Materials Research Articles

Trends of Dye Removal and Heavy Metal Removal of Different Hydrogel-Based Materials and Their Mixtures

Background Hydrogels are relatively newly developed materials that has piqued the curiosity of scientists in various fields, particularly for wastewater treatment applications. Heavy metal ions and dye removal hydrogels is becoming more popular due to its ease of use, low cost, increased effectiveness, biodegradability, and reusability. Objective Evaluate and study the adsorption behaviour of different hydrogel materials towards heavy metal ions and dyes. Methods The hydrogels investigated are Poly(2-Acrylamido-2-Methylpropane Sulphonic Acid) (PAMPS) hydrogels, commercial sodium polyacrylates (Na-PA), chitosan (CH), along with their binary and ternary mixtures. A semi-interpenetrating network (IPN) based on PAMPS and Na-PA was also investigated. The performance of each hydrogel towards six different heavy metals (Co+2, Cu+2, Ni+2, Cd+2, Zn+2, and Mn+2), cationic Methylene Blue (MB) dye, and anionic Methyl Orange (MO) dye, was studied and analysed. Results It was found that the Na-PA/CH hydrogel was the best performing hydrogel for heavy metal removal, removing more than 84% of all metals, followed by PAMPS/Na-PA which removed up to 70%. The best hydrogel mixture with both cationic and anionic dyes is PAMPS/CH, removing 90.1% and 85%, respectively. The proposed dye removal mechanism is electrostatic attraction between the dyes and the charged functional groups on the hydrogel’s surface. Conclusion It is concluded that the use of Na-PA with CH for heavy metal removal yields better results than when using each hydrogel separately. For dye removal, it was found that combining PAMPS with CH creates a very promising hydrogel suitable for removing both anionic and cationic dyes, which is critical for industrial applications.

How Efficient are Alendronate-Nano/Biomaterial Combinations for Anti-Osteoporosis Therapy? An Evidence-Based Review of the Literature.

Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Because of the systemic nature of osteoporosis, the associated escalation in fracture risk affects virtually all skeletal sites. The problem is serious since it is estimated that more than 23 million men and women are at high risk of osteoporotic-like breakages in the European Union. Alendronate (ALN) is the most commonly prescribed oral nitrogen-containing bisphosphonate (BP) for the prevention and the therapy of osteoporosis. This is also one of the most intensely studied drugs in this field. However, ALN is characterized by restricted oral absorption and bioavailability and simultaneously its administration has serious side-effects (jaw osteonecrosis, irritation of the gastrointestinal system, nausea, musculoskeletal pain, and cardiovascular risks). Therefore, delivery systems enabling controlled release and local action of this drug are of great interest, being widely researched and presented in the literature. In this review, we discuss the current trends in the design of various types of alendronate carriers. Our paper is focused on the most recent developments in the field of nano/biomaterials-based systems for ALN delivery, including nano/microformulations, synthetic/natural polymeric and inorganic materials, hydrogel-based materials, scaffolds, coated-like structures, as well as organic-inorganic hybrids. Topics related to the treatment of complex bone diseases including osteoporosis have been covered in several more general reviews; however, the systems for this particular drug have not yet been discussed in detail.

Swelling-Dependent Shape-Based Transformation of a Human Mesenchymal Stromal Cells-Laden 4D Bioprinted Construct for Cartilage Tissue Engineering.

3D bioprinting is usually implemented on flat surfaces, posing serious limitations in the fabrication of multilayered curved constructs. 4D bioprinting, combining 3D bioprinting with time-dependent stimuli-induced transformation, enables the fabrication of shape-changing constructs. Here, a 4D biofabrication method is reported for cartilage engineering based on the differential swelling of a smart multi-material system made from two hydrogel-based materials: hyaluronan and alginate. Two ink formulations are used: tyramine-functionalized hyaluronan (HAT, high-swelling) and alginate with HAT (AHAT, low-swelling). Both inks have similar elastic, shear-thinning, and printability behavior. The inks are 3D printed into a bilayered scaffold before triggering the shape-change by using liquid immersion as stimulus. In time (4D), the differential swelling between the two zones leads to the scaffold's self-bending. Different designs are made to tune the radius of curvature and shape. A bioprinted formulation of AHAT and human bone marrow cells demonstrates high cell viability. After 28 days in chondrogenic medium, the curvature is clearly present while cartilage-like matrix production is visible on histology. A proof-of-concept of the recently emerged technology of 4D bioprinting with a specific application for the design of curved structures potentially mimicking the curvature and multilayer cellular nature of native cartilage is demonstrated.

ECM-Mimicking Hydrogels Loaded with Bone Mesenchymal Stem Cell-Derived Exosomes for the Treatment of Cartilage Defects.

It is well-established that treating articular cartilage injuries is clinically challenging since they lack blood arteries, nerves, and lymphoid tissue. Recent studies have revealed that bone marrow stem cell-derived exosomes (BMSCs-Exos) exert significant chondroprotective effects through paracrine secretions, and hydrogel-based materials can synergize the exosomes through sustained release. Therefore, this research aims to synthesize an ECM (extracellular matrix)-mimicking gelatin methacryloyl (GelMA) hydrogel modified by gelatin combined with BMSCs-derived exosomes to repair cartilage damage. We first isolated and characterized exosomes from BMSCs supernatant and then loaded the exosomes into GelMA hydrogel to investigate cartilage repair effects in in vitro and in vivo experiments. The outcomes showed that the GelMA hydrogel has good biocompatibility with a 3D (three-dimensional) porous structure, exhibiting good carrier characteristics for exosomes. Furthermore, BMSCs-Exos had a significant effect on promoting chondrocyte ECM production and chondrocyte proliferation, and the GelMA hydrogel could enhance this effect through a sustained-release effect. Similarly, in vivo experiments showed that GelMA-Exos promoted cartilage regeneration in rat joint defects and the synthesis of related cartilage matrix proteins.

A study on the thermal responsive behavior of hydrogel-based materials and their potential use in medical applications

PurposeThe purpose of this paper is to present synthesis protocol of hydrogel composed of Chitosan (CS) and Poly(ethylene glycol) (PEG) and establish an understanding of its thermal responsive behavior. It aims to prove the basic temperature sensing ability of a novel CS-PEG-based hydrogel and define its sensing span.Design/methodology/approachThis study includes synthesis of CS and PEG-based hydrogel samples by first performing dissolution of both constituents, respectively, and then adding Glutaraldehyde as the cross-linking agent. It further includes proposed hydrogel’s swelling studies and dynamic behavior testing, followed by hydrogel characterization by Fourier transform infrared spectroscopy, X-ray diffraction and SEM. The last section focuses on the use of proposed hydrogel as a temperature sensor.FindingsDetailed experimental results show that a hydrogel comprising of CS and PEG presents a thermally responsive behavior. It offers potential to be used as a temperature responsive hydrogel-based sensor which could be used in medical applications.Originality/valueThis research study presents scope for future research in the field of thermally responsive bio-sensors. It provides basis for the fabrication of a thermal responsive sensor system based on hydrogels that can be used in specific medical applications.

Nacre-inspired underwater superoleophobic films with high transparency and mechanical robustness.

Underwater superoleophobic materials have attracted increasing attention because of their remarkable potential applications, especially antifouling, self-cleaning and oil-water separation. A limitation of most superoleophobic materials is that they are non-transparent and have limited mechanical stability underwater. Here, we report a protocol for preparing a transparent and robust superoleophobic film that can be used underwater. It is formed by a hydrogel layer prepared by the superspreading of chitosan solution on a superhydrophilic substrate and biomimetic mineralization of this layer. In contrast to conventional hydrogel-based materials, this film exhibits significantly improved mechanical properties because of the combination of high-energy, ordered, inorganic aragonite (one crystalline polymorph of calcium carbonate) and homogeneous external hierarchical micro/nano structures, leading to robust underwater superoleophobicity and ultralow oil adhesion. Moreover, the mineralized film is suitable for neutral and alkaline environments and for containing organic solvent underwater and can be coated on different transparent materials, which has promising applications in underwater optics, miniature reactors and microfluidic devices. In this protocol, the time for the whole biomimetic mineralization process is only ~6 h, which is significantly shorter than that of traditional methods, such as gas diffusion and the Kitano method. The protocol can be completed in ~2 weeks and is suitable for researchers with intermediate expertise in organic chemistry and inorganic chemistry.

Multiparametric Material Functionality of Microtissue-Based InVitro Models as Alternatives to Animal Testing.

With the definition of the 3R principle by Russel and Burch in 1959, the search for an adequate substitute for animal testing has become one of the most important tasks and challenges of this time, not only from an ethical, but also from a scientific, economic, and legal point of view. Microtissue‐based in vitro model systems offer a valuable approach to address this issue by accounting for the complexity of natural tissues in a simplified manner. To increase the functionality of these model systems and thus make their use as a substitute for animal testing more likely in the future, the fundamentals need to be continuously improved. Corresponding requirements exist in the development of multifunctional, hydrogel‐based materials, whose properties are considered in this review under the aspects of processability, adaptivity, biocompatibility, and stability/degradability.

Nitric Oxide-Releasing Bacterial Cellulose/Chitosan Crosslinked Hydrogels for the Treatment of Polymicrobial Wound Infections.

Polymicrobial wound infections are a major cause of infectious disease-related morbidity and mortality worldwide. In this study, we prepared a nitric oxide (NO)-releasing oxidized bacterial cellulose/chitosan (BCTO/CHI) crosslinked hydrogel to effectively treat polymicrobial wound infections. Linear polyethyleneimine diazeniumdiolate (PEI/NO) was used as the NO donor. The aldehyde group of BCTO and the amine of CHI were used as crosslinked hydrogel-based materials; their high NO loading capacity and antibacterial activity on the treatment of polymicrobial-infected wounds were investigated. The blank and NO-loaded crosslinked hydrogels, namely BCTO-CHI and BCTO-CHI-PEI/NO, were characterized according to their morphologies, chemical properties, and drug loading. BCTO-CHI-PEI/NO exhibited sustained drug release over four days. The high NO loading of BCTO-CHI-PEI/NO enhanced the bactericidal efficacy against multiple bacteria compared with BCTO-CHI. Furthermore, compared with blank hydrogels, BCTO-CHI-PEI/NO has a favorable rheological property due to the addition of a polymer-based NO donor. Moreover, BCTO-CHI-PEI/NO significantly accelerated wound healing and re-epithelialization in a mouse model of polymicrobial-infected wounds. We also found that both crosslinked hydrogels were nontoxic to healthy mammalian fibroblast cells. Therefore, our data suggest that the BCTO-CHI-PEI/NO developed in this study improves the efficacy of NO in the treatment of polymicrobial wound infections.

Hydrogel: An Encouraging Nanocarrier System for the Delivery of Herbal Bioactive Compounds

Herbal medicine is a significant component of traditional medicine and has been a part of the treatment of many diseases. Asian people are using herbal medicines for decades. Still, the therapeutic efficacy and pharmaceutical application of herbal extracts encounter difficulties associated with many factors, such as poor bioavailability, low solubility, permeability and lack of targeting potential. Hydrogels are a hydrophilic polymeric network and able to permeate a significant volume of fluids. Hydrogels are biologically compatible and can allow for the sustained release of drugs. These have thus attracted the attention of extensive pharmaceutical formulation studies. The present article first provides a general overview of the hydrogel as a professional nanocarrier. Secondly, the relationship between hydrogel properties and carrier efficiency deliberation has been discussed. In the end, the focus is on the latest technological progress over hydrogel-based materials as herbal medicine carriers. The potential application of hydrogel systems as a carrier for herbal bioactive delivery has shown remarkable promise. This study would be helpful for researchers in the relevant field to understand the most recent advancements in the production of hydrogel-based elements as a vehicle for the delivery of herbal drugs.

Tough and Resilient Hydrogels Enabled by a Multifunctional Initiating and Cross-Linking Agent.

Many high-strength hydrogels have been developed in recent years; however, few of them are both tough and resilient, and their intrinsic paradoxical nature makes designing a gel with both high toughness and high resilience a great challenge. To address this problem, we introduced both N,N,N,N-pentamethyldiethylenetriamine (PA) and N,N-methylenebisacrylamide (MBA) into polyacrylamide hydrogel networks to construct an entangled network that contains chemically cross-linked chains and branched chains simultaneously. The entanglements of branched chains can act as a physical cross-linking point to uniformly disperse stress on molecular chains, and chemical cross-linking ensures the stability of the hydrogel network. The increase in the number and length of branched chains is able to achieve an enhancement in strength while the slip of the entangled polymer chains can effectively achieve energy dissipation and can improve the toughness of the gel. Moreover, the resultant hydrogels exhibit an excellent resilience (>98%). Therefore, high toughness and resilience are achieved simultaneously. In addition, we also investigated the initiation mechanism of PA. This strategy creates a new way for the preparation of next-generation high toughness and high resilience hydrogel-based materials, which have promising applications in wearable, flexible strain/pressure sensors.

Effect of Washing Treatment on the Textural Properties and Bioactivity of Silica/Chitosan/TCP Xerogels for Bone Regeneration.

Silica/biopolymer hydrogel-based materials constitute very attractive platforms for various emerging biomedical applications, particularly for bone repair. The incorporation of calcium phosphates in the hybrid network allows for designing implants with interesting biological properties. Here, we introduce a synthesis procedure for obtaining silica–chitosan (CS)–tricalcium phosphate (TCP) xerogels, with CS nominal content varying from 4 to 40 wt.% and 10 to 20 wt.% TCP. Samples were obtained using the sol-gel process assisted with ultrasound probe, and the influence of ethanol or water as washing solvents on surface area, micro- and mesopore volume, and average pore size were examined in order to optimize their textural properties. Three washing solutions with different soaking conditions were tested: 1 or 7 days in absolute ethanol and 30 days in distilled water, resulting in E1, E7, and W30 washing series, respectively. Soaked samples were eventually dried by evaporative drying at air ambient pressure, and the formation of interpenetrated hybrid structures was suggested by Fourier transformed infrared (FTIR) spectroscopy. In addition the impact that both washing solvent and TCP content have on the biodegradation, in vitro bioactivity and osteoconduction of xerogels were explored. It was found that calcium and phosphate-containing ethanol-washed xerogels presented in vitro release of calcium (2–12 mg/L) and silicon ions (~60–75 mg/L) after one week of soaking in phosphate-buffered saline (PBS), as revealed by inductive coupled plasma (ICP) spectroscopy analysis. However, only the release of silicon was detected for water-washed samples. Besides, all the samples exhibited in vitro bioactivity in simulated body fluid (SBF), as well as enhanced in vitro cell growth and also significant focal adhesion development and maturation.

Development of Conductive Gelatine-Methacrylate Inks for Two-Photon Polymerisation.

Conductive hydrogel-based materials are attracting considerable interest for bioelectronic applications due to their ability to act as more compatible soft interfaces between biological and electrical systems. Despite significant advances that are being achieved in the manufacture of hydrogels, precise control over the topographies and architectures remains challenging. In this work, we present for the first time a strategy to manufacture structures with resolutions in the micro-/nanoscale based on hydrogels with enhanced electrical properties. Gelatine methacrylate (GelMa)-based inks were formulated for two-photon polymerisation (2PP). The electrical properties of this material were improved, compared to pristine GelMa, by dispersion of multi-walled carbon nanotubes (MWCNTs) acting as conductive nanofillers, which was confirmed by electrochemical impedance spectroscopy and cyclic voltammetry. This material was also confirmed to support human induced pluripotent stem cell-derived cardiomyocyte (hPSC-CMs) viability and growth. Ultra-thin film structures of 10 µm thickness and scaffolds were manufactured by 2PP, demonstrating the potential of this method in areas spanning tissue engineering and bioelectronics. Though further developments in the instrumentation are required to manufacture more complex structures, this work presents an innovative approach to the manufacture of conductive hydrogels in extremely low resolution.

Emerging Role of Hydrogels in Drug Delivery Systems, Tissue Engineering and Wound Management.

The popularity of hydrogels as biomaterials lies in their tunable physical properties, ability to encapsulate small molecules and macromolecular drugs, water holding capacity, flexibility, and controllable degradability. Functionalization strategies to overcome the deficiencies of conventional hydrogels and expand the role of advanced hydrogels such as DNA hydrogels are extensively discussed in this review. Different types of cross-linking techniques, materials utilized, procedures, advantages, and disadvantages covering hydrogels are tabulated. The application of hydrogels, particularly in buccal, oral, vaginal, and transdermal drug delivery systems, are described. The review also focuses on composite hydrogels with enhanced properties that are being developed to meet the diverse demand of wound dressing materials. The unique advantages of hydrogel nanoparticles in targeted and intracellular delivery of various therapeutic agents are explained. Furthermore, different types of hydrogel-based materials utilized for tissue engineering applications and fabrication of contact lens are discussed. The article also provides an overview of selected examples of commercial products launched particularly in the area of oral and ocular drug delivery systems and wound dressing materials. Hydrogels can be prepared with a wide variety of properties, achieving biostable, bioresorbable, and biodegradable polymer matrices, whose mechanical properties and degree of swelling are tailored with a specific application. These unique features give them a promising future in the fields of drug delivery systems and applied biomedicine.

Impacts of Mechanical Stiffness of Bacteriophage-Loaded Hydrogels on Their Antibacterial Activity.

The elaboration of efficient hydrogel-based materials with antimicrobial properties requires a refined control of defining their physicochemical features, which includes mechanical stiffness, so as to properly mediate their antibacterial activity. In this work, we design hydrogels consisting of polyelectrolyte multilayer films for the loading of T4 and φX174 bacteria-killing viruses, also called bacteriophages. We investigate the antiadhesion and bactericidal performances of this biomaterial against Escherichia coli, with a specific focus on the effects of chemical cross-linking of the hydrogel matrix, which, in turn, mediates the hydrogel stiffness. Depending on the latter and on phage replication features, it is found that the hydrogels loaded with the bacteria-killing viruses make both contact killing (targeted bacteria are those adhered at the hydrogel surface) and release killing (planktonic bacteria are the targets) possible with ca. 20-80% efficiency after only 4 h of incubation at 25 °C as compared to cases where hydrogels are free of viruses. We further demonstrate the lack of dependence of virus diffusion within the hydrogel and of the maximal viral storage capacity on the hydrogel mechanical properties. In addition to the evidenced bacteriolytic activity of the phages loaded in the hydrogels, the antimicrobial property of the phage-loaded materials is shown to be partly controlled by the chemistry of the hydrogel skeleton and, more specifically, by the mobility of the peripheral free polycationic components, known for their ability to weaken and permeabilize membranes of bacteria, the latter then becoming "easier" targets for the viruses.

A Composite Hydrogel Based on Pectin/Cellulose via Chemical Cross-Linking for Hemorrhage.

Hydrogel-based material have been demonstrated promising potential for hemostasis. Herein, we prepared a composite hydrogel (CH-P 40%) by combining pectin and cellulose in ionic liquid. The superficial morphology of the CH-P 40% was explored by SEM; the internal chemical bonds, crystal form and thermal stability were determined via FTIR, XRD and thermogravimetric analysis, respectively. The biocompatibilities of the CH-P 40% hydrogel was evaluated by MTT, flow cytometry, and histological observation with H&E staining. Furthermore, the hemostatic effect was evaluated via the blood clotting index and mouse liver hemostatic model. The results showed that the CH-P 40% hydrogel exhibited a dense network structure and retained its chemical bonds, including the OH, CH, C=O, -CH2, CO, C1-H, and β-glycosidic bonds. Simultaneously, the hydrogel retained the Cellulose I and II crystal structure and favorable thermal stability. Moreover, the proliferation rates of CH-P 40%-treated cells increased (P > 0.05), and there were no pathological lesions in the mouse organs, which suggests favorable biocompatibility. The results showed less bleeding in the hydrogel-treated liver wound within 3 min. Overall, the pectin-cellulose hydrogel is stable and possesses favorable biocompatibility and hemostatic ability, further highlighting that the composite hydrogel has the potential to be rapid hemostatic biomedical material.

Controlling Growth Factor Diffusion by Modulating Water Content in Injectable Hydrogels.

Recent advancements in the delivery of therapeutics for retinal diseases include the development of injectable hydrogels, networks of one or more hydrophilic polymers that contain a high-volume fraction of water. These systems are of particular interest due to their biocompatibility, permeability to water-soluble metabolites, and function as minimally invasive injectable delivery vehicles. Recently, hydrogels for ophthalmic applications have been developed that display a controlled release of factors necessary for cellular survival and proliferation. Understanding the relationship between the volume water fraction and the physical, chemical, and diffusion properties of the hydrogel scaffold could aid in the improvement of existing drug delivery treatments for retinal regeneration. In this study, we compared the diffusion and release of human epidermal growth factor (hEGF) encapsulated in different injectable homogenous and heterogenous hydrogels, namely gelatin-hydroxyphenyl propionic acid (Gtn-HPA) and hyaluronic acid-tyramine (HA-Tyr)-based hydrogels. These experimental results were compared with the measured stiffness and water content of these hydrogels and applied to different diffusion theories of polymers to determine the model of best fit. We find that the normalized diffusion and release of hEGF increases with free water content in injectable hydrogels: ranging from 0.176 at 41% free water in HA-Tyr to 0.2 at 53% free water in Gtn-HPA, whereas it decreases with hydrogel stiffness: 600 Pa for Gtn-HPA and 1440 Pa for HA-Tyr. Further, we compared our experimental data with theoretical diffusion models. We found that homogeneous theoretical models, notably the hydrodynamic model (giving a normalized diffusion close to 0.2), provide the most suitable explanation for the measured solute diffusion coefficient. Impact statement Diffusion in a three-dimensional system is a key factor in designing new hydrogel-based materials. It allows to control and predict diffusion in implants and delivery systems. However, very little is done to explore and test the diffusion since it is a complex process. Many models can predict solute diffusion; however, practical application using these models has not yet been done. We have shown the variation of these models in a practical extent, which could have a tremendous impact on designing biomaterial for biological application as it allows one to understand the diffusion of injected drugs and growth factors.

Influence of the Degree of Deacetylation of Chitosan and BMP-2 Concentration on Biocompatibility and Osteogenic Properties of BMP-2/PLA Granule-Loaded Chitosan/β-Glycerophosphate Hydrogels.

Compositions based on chitosan/β-glycerophosphate hydrogels with highly porous polylactide granules can be used to obtain moldable bone graft materials that have osteoinductive and osteoconductive properties. To eliminate the influence of such characteristics as chain length, degree of purification, and molecular weight on a designed material, the one-stock chitosan sample was reacetylated to degrees of deacetylation (DD%) of 19.5, 39, 49, 55, and 56. A study of the chitosan/β-glycerophosphate hydrogel with chitosan of a reduced DD% showed that a low degree of deacetylation increased the MSCs (multipotent stromal cells) viability rate in vitro and reduced the leukocyte infiltration in subcutaneous implantation to Wistar rats in vivo. The addition of 12 wt% polylactide granules resulted in optimal composite mechanical and moldable properties, and increased the modulus of elasticity of the hydrogel-based material by approximately 100 times. Excessive filling of the material with PLA (polylactide) granules (more than 20%) led to material destruction at a ~10% strain. Osteoinductive and osteoconductive properties of the chitosan hydrogel-based material with reacetylated chitosan (39 DD%) and highly porous polylactide granules impregnated with BMP-2 (bone morphogenetic protein-2) have been demonstrated in models of orthotopic and ectopic bone formation. When implanted into a critical-size calvarial defect in rats, the optimal concentration of BMP-2 was 10 μg/mL: bone tissue areas filled the entire material’s thickness. Implantation of the material with 50 μg/mL BMP-2 was accompanied with excessive growth of bone tissue and material displacement beyond the defect. Significant osteoinductive and osteoconductive properties of the material with 10 μg/mL of BMP-2 were also shown in subcutaneous implantation.

Mechanochemical Cellular Membrane Internalization of Nanohydrogels: A Large-Scale Mesoscopic Simulation.

By combining large-scale dissipative particle dynamics and steered molecular dynamics simulations, we investigate the mechanochemical cellular internalization pathways of homogeneous and heterogeneous nanohydrogels and demonstrate that membrane internalization is determined by the crosslink density and encapsulation ability of nanohydrogels. The homogeneous nanohydrogels with a high crosslink density and low encapsulation ability behave as soft nanoparticles partially wrapped by the membrane, while those with a low crosslink density and high encapsulation ability permeate into the membrane. Regardless of the crosslink density, the homogeneous nanohydrogels undergo typical dual morphological deformations. The local lipid nanodomains are identified at the contacting region between the membrane and nanohydrogels because of different diffusion behaviors between lipid and receptor molecules during the internalization process. The yolk@shell heterogeneous nanohydrogels present a different mechanochemical cellular internalization pathway. The yolk with strong affinity is directly in contact with the membrane, resulting in partial membrane wrapping, and the contacting area is much reduced when compared to homogenous nanohydrogels, leading to a smaller lipid nanodomain and thus avoiding related cellular toxicity. Our findings provide a critical mechanism understanding of the biological pathways of nanohydrogels and may guide the molecular design of the hydrogel-based materials for controlled release drug delivery, tissue engineering, and cell culture.

Recombinant collagen polypeptide as a versatile bone graft biomaterial

Autografts and allografts are currently considered the gold standard for grafting surgery; however, to meet the growing demand in fast-aging societies, synthetic biomaterials will play an increasingly important role. Here we report a biodegradable scaffold material composed of recombinant polypeptide based on the human type I collagen alpha 1 chain (RCPhC1) as a source of hydrogel-based graft materials. The flexibility to engineer ideal characteristics for bone grafts was demonstrated. The critical internal isotropic pore structure was generated through a designed thin-layer freeze casting process. The optimized biodegradation rate was controlled by dehydrothermal crosslinking by adjusting the amino acid composition of RCPhC1. As a result, RCPhC1 bone grafts manufactured by a highly scalable streamlined production protocol induced robust regeneration of mature bone tissue while being completely resorbed in pre-clinical animal models.

Facilitate Angiogenesis and Neurogenesis by Growth Factors Integrated Decellularized Matrix Hydrogel.

Neurological functional recovery depends on the synergistic interaction between angiogenesis and neurogenesis after peripheral nerve injury (PNI). Decellularized nerve matrix hydrogels have drawn much attention and been considered as potential therapeutic biomaterials for neurovascularization, due to their intrinsic advantages in construction of a growth-permissive microenvironment, strong affinity to multiple growth factors (GFs), and promotion of neurite outgrowth. In the present study, nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) were incorporated into porcine decellularized nerve matrix hydrogel (pDNM-gel) for PNI treatment. Both GFs bound strongly to pDNM-gel and underwent a controlled release manner, which showed facilitated axonal extension and vascular-like tube formation in vitro. Especially, a companion growth was identified when human umbilical vein endothelial cells and neurons were cocultured on the GFs containing pDNM-gel. In a crushed rat sciatic nerve model, the incorporated NGF and VEGF appeared to contribute for axonal growth and neovascularization correspondingly but separately. Both GFs were equally important in improving nerve functional recovery after in situ administration. These findings indicate that pDNM-gel is not only a bioactive hydrogel-based material that can be used alone, but also serves as suitable carrier of multiple GFs for promoting an effective PNI repair. Impact statement Decellularized matrix hydrogel derived from nerve tissue has demonstrated its effectiveness in promoting nerve reinnervation, remyelination, and functionalization. Meanwhile, angiogenesis is highly desirable for treatment of long-distance peripheral nerve defects. To this end, we incorporated both vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) into porcine decellularized nerve matrix hydrogel (pDNM-gel) to induce neovascularization and neuroregeneration. At the cellular level, the pDNM-gel with both growth factors (GFs) exhibited significant capability in promoting axonal elongation, Schwann cell proliferation and migration, as well as vessel/nerve interaction. In crushed peripheral nerve injury (PNI) rat model, the integrated VEGF was more favorable for angiogenesis, whereas NGF mainly contributed to neurogenesis. However, the combination of both GFs in pDNM-gel highly facilitated motor functional recovery, highlighting the therapeutic promise of decellularized matrix hydrogel for growth factor delivery toward neuroprotection and neuroregeneration after PNI.