Genipin Crosslinking Research Articles

Genipin crosslinking reduced the immunogenicity of xenogeneic decellularized porcine whole-liver matrices through regulation of immune cell proliferation and polarization.

Decellularized xenogeneic whole-liver matrices are plausible biomedical materials for the bioengineering of liver transplantation. A common method to reduce the inflammatory potential of xenogeneic matrices is crosslinking. Nevertheless, a comprehensive analysis of the immunogenic features of cross-linked decellularized tissue is still lacking. We aimed to reduce the immunogenicity of decellularized porcine whole-liver matrix through crosslinking with glutaraldehyde or genipin, a new natural agent, and investigated the mechanism of the immune-mediated responses. The histologic assessment of the host’s immune reaction activated in response to these scaffolds, as well as the M1/M2 phenotypic polarization profile of macrophages, was studied in vivo. The genipin-fixed scaffold elicited a predominantly M2 phenotype response, while the glutaraldehyde-fixed scaffold resulted in disrupted host tissue remodeling and a mixed macrophage polarization profile. The specific subsets of immune cells involved in the responses to the scaffolds were identified in vitro. Crosslinking alleviated the host response by reducing the proliferation of lymphocytes and their subsets, accompanied by a decreased release of both Th1 and Th2 cytokines. Therefore, we conclude that the natural genipin crosslinking could lower the immunogenic potential of xenogeneic decellularized whole-liver scaffolds.

Tendon Collagen Crosslinking Offers Potential to Improve Suture Pullout in Rotator Cuff Repair: An Ex Vivo Sheep Study.

The suture-tendon interface is often the weakest link in tendon to bone repair of massive rotator cuff tears. Genipin is a low-toxicity collagen crosslinker derived from the gardenia fruit that has been shown to augment collagen tissue strength and mechanically arrest tendon-tear progression. The purpose of the current study was to evaluate whether genipin crosslinking can sufficiently augment the suture-tendon interface to improve suture pullout strength using simple single-loop sutures and the modified Mason-Allen technique. The study also aimed to assess whether time of genipin treatment is a relevant factor in efficacy. In an ex vivo (cadaveric) sheep rotator cuff tendon model, a total of 142 suture pullout tests were performed on 32 infraspinatus tendons. Each tendon was prepared with three single-loop stitches. Two groups were pretreated by incubation in genipin solution for either 4 hours or 24 hours. Two corresponding control groups were incubated in phosphate buffered saline for the same periods. The same test protocol was applied to tendons using modified Mason-Allen technique stitch patterns. Each suture was loaded to failure on a universal materials testing machine. Suture pullout force, stiffness, and work to failure were calculated from force-displacement data, and then compared among the groups. Median single-loop pullout force on tendons incubated for 24 hours in genipin yielded an approximately 30% increase in maximum pullout force for single-loop stitches with a median of 73 N (range, 56-114 N) compared with 56 N (range, 40-69 N; difference of medians = 17 N; p = 0.028), with corresponding increases in the required work to failure but not stiffness. Genipin treatment for 4 hours showed no added benefit for suture-pullout behavior (46 N, [range, 35-95 N] versus 45 N, [range, 28-63 N]; difference of medians, 1 N; p = 1). No tested genipin crosslinking conditions indicated benefit for tendons grasped using the modified Mason-Allen technique after 4 hours (162 N, [range, 143-193 N] versus 140 N, [range, 129-151 N]; difference of medians, 22 N; p = 0.114) or after 24 hours of crosslinking (172 N, [range, 42-183 N] versus 164 N [range, 151-180 N]; difference of medians, 8 N; p = 0.886). Exogenous collagen crosslinking in genipin can markedly improve resistance to pullout at the tendon-suture interface for simple stitch patterns while the modified Mason-Allen stitch showed no benefit in an ex vivo animal model. Tendon strength augmentation by genipin pretreatment offers the potential to improve suture retention properties. Future studies are warranted for the development of clinically viable intraoperative delivery strategies and in vivo testing for safety and efficacy.

Enhancing the biological response of titanium surface through the immobilization of bone morphogenetic protein-2 using the natural cross-linker genipin

Titanium (Ti) is widely used in orthopaedic and dental implants; however, the surface modification methods used to promote osseointegration require further development. In this study, we developed a simple, cost-effective method for the immobilization of bone morphogenetic protein-2 (BMP-2) on Ti surfaces using a natural cross-linker genipin. We then investigated the surface characteristics, including topography, chemistry, hydrophilicity, coating layer adhesion, and protein (albumin) adsorption. In accordance with ISO 10993-5, the cytotoxicity of the resulting materials was evaluated. Human bone marrow mesenchymal stem cell responses, including adhesion, proliferation, and mineralization, were also evaluated. Immersion in alkaline solution resulted in the formation of a porous Ti surface. The use of the cross-linker genipin for the immobilization of BMP-2 on porous Ti surfaces improved the surface hydrophilicity and protein adsorption, which resulted in a non-cytotoxic coating with good adhesion characteristics. The immobilization of BMP-2 on porous Ti surfaces was shown to significantly increase cell mineralization and bioactivity (i.e. Ca/P formation ability), resulting in a biomolecular surface with outstanding potential for bone implant applications.

An efficient thermophilic histone-polyethylenimine hybrid gene carrier through the genipin crosslinking

An efficient thermophilic histone-polyethylenimine hybrid gene carrier through the genipin crosslinking

Tough and strong nacre-like composites from hyperbranched poly(amido amine) and clay nanosheets cross-linked by genipin

Tough and strong nacre-like composite films were fabricated from hyperbranched poly(amido amine) (HPAMAM) and clay nanosheets with the aid of genipin crosslinking.

Investigation of in Vitro Release Dynamics of Cisplatin from Genipin Crosslinked Gelatin Nanocarriers

Background: Emergence of new synthetic methods has given great impetus and momentum to nanotechnology which has revolutionized almost all disciplines of science and technology including medicine and pharmacy. The most fascinating aspect of nanomaterials is their vital role in drug delivery technology that makes use of them as drug carrying vehicles and delivers the carried drug to the diseased site in pre-determined amount. The present work aims at designing genipin crosslinked nanocarriers of gelatin and studying release of cisplatin drug under varying experimental conditions. Methods: The genipin crosslinked nanoparticles of gelatin were prepared by emulsion crosslinking method and the nanoparticles were characterized by techniques like FTIR, SEM, TEM and particle size analysis. The nanocarriers were loaded with cisplatin and the release of drug was monitored spetrophotometrically. Results: The size of nanoparticles was found up to 150 nm and the FTIR spectra confirmed the crosslinking of gelatin by genipin. The release of cisplatin was found to increase with increasing percent loading of drug. The amount of released cisplatin was significantly dependent on the amount of gelatin and genipin. The amounts of released drug at acidic and alkaline pH were greater than that released at neutral medium. The drug was found to decrease with increasing temperature of the release medium. Conslusions: The emulsion crosslinking of gelatin with genipin results in a swelling controlled drug delivery system which may be successfully used to achieve controlled release of cisplatin type of drug. The nanoparticles produced are quite nanosize in dimension and offer greater loading of drug which may desirably be released with precise control over its amount. Keywords: Cisplatin, drug delivery, gelatin, nanoparticles.

Genipin-crosslinked, immunogen-reduced decellularized porcine liver scaffold for bioengineered hepatic tissue

Liver disease affects millions of patients each year worldwide. Decellularized biologic matrices are plausible biomedical materials for bioengineered replacement hepatic tissue. However, one of the concerns for its safe medical application is the lack of objective assessment of the immunogen within the materials and in vivo immune responses to the matrices. The purpose of this study was to produce immunogen- reduced and biocompatible matrices from porcine liver. Whole porcine livers were perfusion decellularized and cross-linked with glutaraldehyde (GA) or genipin (GP). Proteins were extracted, and the migratory response of human leukocytes toward protein extracts was examined using an in vitro migration chamber. In addition, biopsy specimens of decellularized scaffolds were implanted subcutaneously into rodents to investigate scaffold immunogenicity. Histological staining confirmed cellular clearance from pig livers, with removal of nuclei and cytoskeletal components and widespread preservation of structural extracellular molecules. Polymerase chain reaction analysis showed that galactose-alpha-1,3-galactose-beta-1,4-N-acetylglucosamine (1,3 gal), swine leukocyte antigen, and porcine endogenous retrovirus were completely removed in the matrices. Decellularization significantly reduced the migration of monocytes compared with native porcine tissue. Although the proportion of transmigrating lymphocytes was much lower, repeating the cross-linking procedure reduced the migratory response. After implantation for 4 weeks, the decellularized and native samples were degraded, and the GA-treated group demonstrated a severe inflammatory reaction; however, minimal inflammatory cell infiltration was seen in the GPtreated group during the 8-week investigation period. In conclusion, our study provided evidence that GP crosslinking could significantly reduce the immunogenicity of decellularized liver biomaterials.

Highly Compliant Vascular Grafts with Gelatin-Sheathed Coaxially Structured Nanofibers.

We have developed three types of materials composed of polyurethane-gelatin, polycaprolactone-gelatin, or polylactic acid-gelatin nanofibers by coaxially electrospinning the hydrophobic core and gelatin sheath with a ratio of 1:5 at fixed concentrations. Results from attenuated total reflection-Fourier transformed infrared spectroscopy demonstrated the gelatin coating around nanofibers in all of the materials. Transmission electron microscopy images further displayed the core-sheath structures showing the core-to-sheath thickness ratio varied greatly with the highest ratio found in polyurethane-gelatin nanofibers. Scanning electron microscopy images revealed similar, uniform fibrous structures in all of the materials, which changed with genipin cross-linking due to interfiber interactions. Thermal analyses revealed varied interactions between the hydrophilic sheath and hydrophobic core among the three materials, which likely caused different core-sheath structures, and thus physicomechanical properties. The addition of gelatin around the hydrophobic polymer and their interactions led to the formation of graft scaffolds with tissue-like viscoelasticity, high compliance, excellent swelling capability, and absence of water permeability while maintaining competent tensile modulus, burst pressure, and suture retention. The hydrogel-like characteristics are advantageous for vascular grafting use, because of the capability of bypassing preclotting prior to implantation, retaining vascular fluid volume, and facilitating molecular transport across the graft wall, as shown by coculturing vascular cells sandwiched over a thick-wall scaffold. Varied core-sheath interactions within scaffolding nanofibers led to differences in graft functional properties such as water swelling ratio, compliance, and supporting growth of cocultured vascular cells. The PCL-gelatin scaffold with thick gelatin-sheathed nanofibers demonstrated a more compliant structure, elastic mechanics, and high water swelling property. Our results demonstrate a feasible approach to produce new hybrid, biodegradable nanofibrous scaffold biomaterials with interactive core-sheath structure, good biocompatibility, and tissue-like viscoelasticity, which may reduce potential problems with the use of individual polymers for vascular grafts.

Biosynthesis and Characterization of Cross-Linked Fmoc Peptide-Based Hydrogels for Drug Delivery Applications.

Recently, scientific and technological interest in the synthesis of novel peptide-based hydrogel materials have grown dramatically. Applications of such materials mostly concern the biomedical field with examples covering sectors such as drug delivery, tissue engineering, and production of scaffolds for cell growth, thanks to their biocompatibility and biodegradability. In this work we synthesized Fmoc-Phe3 based hydrogels of different chirality by using a biocatalytic approach. Moreover, we investigated the possibility of employing a crosslinker during the biosynthetic process and we studied and compared some chemico-physical features of both crosslinked and non-crosslinked hydrogels. In particular, we investigated the rheological properties of such materials, as well as their swelling ability, stability in aqueous medium, and their structure by SEM and AFM analysis. Crosslinked and non-crosslinked hydrogels could be formed by this procedure with comparable yields but distinct chemico-physical features. We entrapped dexamethasone within nanopolymeric particles based on PLGA coated or not with chitosan and we embedded these nanoparticles into the hydrogels. Dexamethasone release from such a nanopolymer/hydrogel system was controlled and sustained and dependent on genipin crosslinking degree. The possibility of efficiently coupling a drug delivery system to hydrogel materials seem particularly promising for tissue engineering applications, where the hydrogel could provide cells the necessary support for their growth, while nanoparticles could favor cell growth or differentiation by providing them the necessary bioactive molecules.

PH Responsiveness of Multilayered Films and Membranes Made of Polysaccharides.

We investigated the pH-dependent properties of multilayered films made of chitosan (CHI) and alginate (ALG) and focused on their postassembly response to different pH environments using a quartz crystal microbalance with dissipation monitoring (QCM-D), swelling studies, ζ potential measurements, and dynamic mechanical analysis (DMA). In an acidic environment, the multilayers presented lower dissipation values and, consequently, higher moduli when compared with the values obtained for the pH used during the assembly (5.5). When the multilayers were exposed to alkaline environments, the opposite behavior occurred. These results were further corroborated by the ability of this multilayered system to exhibit a reversible swelling-deswelling behavior within the pH range from 3 to 9. The changes in the physicochemical properties of the multilayer system were gradual and different from those of individual solubilized polyelectrolytes. This behavior is related to electrostatic interactions between the ionizable groups combined with hydrogen bonding and hydrophobic interactions. Beyond the pH range of 3-9, the multilayers were stabilized by genipin cross-linking. The multilayered films also became more rigid while the pH responsiveness conferred by the ionizable moieties of the polyelectrolytes was preserved. This work demonstrates the versatility and feasibility of LbL methodology to generate inherently pH stimulus-responsive nanostructured films. Surface functionalization using pH responsiveness endows several biomedical applications with abilities such as drug delivery, diagnostics, microfluidics, biosensing, and biomimetic implantable membranes.

Exogenous Crosslinking Restores Intradiscal Pressure of Injured Porcine Intervertebral Discs: An In Vivo Examination Using Quantitative Discomanometry.

In vivo examination of intradiscal pressure by quantitative discomanometry (QD). To determine whether an injectable, exogenous crosslinking could acutely restore intradiscal pressure of stab-injured discs in vivo by short-term treatment. Disc biomechanical performance depends on its integrity associated with the intradiscal pressure and mechanical properties. Genipin crosslink augmentation has demonstrated the in vitro biomechanical capability to improve intervertebral joint stability and increase mechanical properties of the annulus fibrosus. 4 lumbar discs on each of 8 swine were randomly assigned to 4 groups: intact, injured, untreated, and crosslinked. A 16G needle was stabbed into the annulus fibrosus to create the disc injury model. An injection of 0.33% genipin solution was delivered into the annulus to treat the injury. QD technique was performed to examine the intradiscal pressure for the intact and injured discs at the time of surgery, while untreated and crosslinked discs were measured 1-week postsurgery. 4 QD parameters were analyzed and compared across the 4 groups: leakage pressure and volume, and saturation pressure and volume. The leakage and saturation pressures of the injured group were significantly lower than those of the intact group (P = 0.004 and P = 0.01, respectively). The leakage and saturation pressures of untreated discs were statistically equivalent to the injured levels, but with a 2-times higher saturation volume. Relative to the untreated group, the leakage pressure and saturation pressure of genipin-crosslinked discs had a 617% (P = 0.008) and a 473% increase (P = 0.007), respectively. A large disc injury produced by annular puncture immediately lowered intradiscal pressure when left untreated. Genipin crosslinking can restore intradiscal pressure acutely in vivo without any obvious morbidity associated with the injection.

Surface modification of electrospun poly(methyl methacrylate) (PMMA) nanofibers for the development of in vitro respiratory epithelium model

Scaffold design is an important aspect of in vitro model development. In this study, nanoscaffold surface modification, namely UV radiation and genipin cross-linking to immobilize collagen on the surface of electrospun poly (methyl methacrylate) (PMMA) nanofiber sheet was investigated. Samples were divided into four groups; PMMA nanofibers (PMMA), collagen-coated PMMA nanofibers (PMMACOL), genipin cross-linked collagen-coated PMMA nanofibers (PMMAGEN), and UV-irradiated collagen-coated PMMA nanofibers (PMMAUV). 6 h of UV radiation significantly reduced the hydrophobicity of PMMA nanofibers from (131.88° ± 1.33°) to (110.04° ± 0.27°) (p < 0.05). The amount of collagen immobilized was significantly higher in PMMAGEN group (239.36 ± 16.63 μg collagen/mg nanofibers) (p < 0.05) compared to the other groups. RECs on all scaffold expressed epithelial cell-specific markers (CK18 and CK14), mucin-producing cell marker (MUC5Ac) and were actively proliferating, based on the positive expression of Ki67. Total number of attached cells was significantly the highest in PMMAUV group on day 9 (6.44 × 104 ± 2.77 × 104 cells/cm2) and it has the highest proliferation rate from day 4 to 9 (0.005 ± 0.003 h−1) compared to the other groups. Even though PMMAGEN group showed the highest collagen adsorption, in terms of cells attachment and proliferation, PMMAUV group showed a better outcome compared to the other groups. Thus, PMMAUV scaffold is more suitable to be used in the construction of in vitro respiratory epithelial model.

Preparation of a biomimetic composite scaffold from gelatin/collagen and bioactive glass fibers for bone tissue engineering

Bone tissue is a composite material made of organic and inorganic components. Bone tissue engineering requires scaffolds that mimic bone nature in chemical and mechanical properties. This study proposes a novel method for preparing composite scaffolds that uses sub-micron bioglass fibers as the organic phase and gelatin/collagen as the inorganic phase. The scaffolds were constructed by using freeze drying and electro spinning methods and their mechanical properties were enhanced by using genipin crosslinking agent.Electron microscopy micrographs showed that the structure of composite scaffolds were porous with pore diameters of approximately 70–200μm, this was again confirmed by mercury porosimetery. These pores are suitable for osteoblast growth. The diameters of the fibers were approximately 150–450nm. Structural analysis confirmed the formation of desirable phases of sub-micron bioglass fibers. Cellular biocompatibility tests illustrated that scaffolds containing copper ion in the bioglass structure had more cell growth and osteoblast attachment in comparison to copper-free scaffolds.

Genipin-cross-linked silk sericin/poly(N-isopropylacrylamide) IPN hydrogels: Color reaction between silk sericin and genipin, pore shape and thermo-responsibility

To investigate the color reactions between naturally cross-linking agent genipin and silk sericin (SS), a series of genipin/SS film with adjustable color were firstly fabricated and analyzed by FTIR, UV/Vis and colorimetric methods. Then under the various genipin/SS contents, double cross-linked genipin/SS/Poly(N-isopropyl- acrylamide/N,N′-Methylene-bis-acrylamide) (HMGX) hydrogels were prepared, and the SEM, DSC, gravimetric and MTT method were performed to investigate pore structure, swelling behavior, temperature-sensitivities and cell adhesion behavior of HMGX hydrogels. The results show that SS cross-linked by genipin presents various colors during reaction. With increasing genipin/SS from 0 to 20 wt% or reacted time from 0 to 250 min, the color of genipin/SS mixture solution changes from transparent yellow to green, then to skyblue and finally became dark blue. After SS was cross-linked genipin, the maximum absorption peak turns to 570–600 nm from 282 nm, the reacted gardenia blue shows thermo/pH stable and water soluble. The absorption values of genipin/SS solutions increase, especially as genipin/SS ratio is 20 wt%, sharply increase can be found. The reaction time or rate between sericin and genipin is dependent on genipin/SS feed ratios. And with increasing mass percentage of genipin/(NIPAm + SS) from 0 to 10 wt%, due to high hydrophilicity of cross-linked product between genipin and SS, the pore sizes of HMGX hydrogels increase 1–3.75 times, the maximum swelling ratios (MSR) values increase to 2243% from 1057%. The volume phase transition temperature (VPTT) values of HMGX hydrogels keep still at 32–36 °C, but the endothermic peak becomes broader. After adsorption of L929 cells for 4 h and 1 d, the hydrogel with 3 wt% of genipin/(NIPAm + SS) presents the highest adhesion percentage.

Multifunctional chitosan/polyvinyl pyrrolidone/45S5 Bioglass® scaffolds for MC3T3-E1 cell stimulation and drug release.

Novel chitosan-polyvinyl pyrrolidone/45S5 Bioglass® (CS-PVP/BG) scaffolds were prepared via foam replication and chemical cross-linking techniques. The pristine BG, CS-PVP coated BG and genipin cross-linked CS-PVP/BG (G-CS-PVP/BG) scaffolds were synthesized and characterized in terms of chemical composition, physical structure and morphology respectively. Resistance to enzymatic degradation of the scaffold is improved significantly with the use of genipin cross-linked CS-PVP. The bio-effects of scaffolds on MC3T3-E1 osteoblast-like cells were evaluated by studying cell viability, adhesion and proliferation. The CCK-8 assay shows that cell viability on the resulting G-CS-PVP/BG scaffold is improved obviously after cross-linking of genipin. Cell skeleton images exhibit that well-stretched F-actin bundles are obtained on the G-CS-PVP/BG scaffold. SEM results present significant improvement on the cell adhesion and proliferation for cells cultured on the G-CS-PVP/BG scaffold. The drug release performance on the as-synthesized scaffold was studied in a phosphate buffered saline (PBS) solution. Vancomycin is found to be released in burst fashion within 24h from the pristine BG scaffold, however, the release period from the G-CS-PVP/BG scaffold is enhanced to 7days, indicating improved drug release properties of the G-CS-PVP/BG scaffold. Our results suggest that the G-CS-PVP/BG scaffolds possess promising physicochemical properties, sustained drug release capability and good biocompatibility for MC3T3-E1 cells' proliferation and adhesion, suggesting their potential applications in areas such as MC3T3-E1 cell stimulation and bone tissue engineering.

Silk Hydrogels of Tunable Structure and Viscoelastic Properties Using Different Chronological Orders of Genipin and Physical Cross-Linking

Catering the hydrogel manufacturing process toward defined viscoelastic properties for intended biomedical use is important to hydrogel scaffolding function and cell differentiation. Silk fibroin hydrogels may undergo "physical" cross-linking through β-sheet crystallization during high pressure carbon dioxide treatment, or covalent "chemical" cross-linking by genipin. We demonstrate here that time-dependent mechanical properties are tunable in silk fibroin hydrogels by altering the chronological order of genipin cross-linking with β-sheet formation. Genipin cross-linking before β-sheet formation affects gelation mechanics through increased molecular weight, affecting gel morphology, and decreasing stiffness response. Alternately, genipin cross-linking after gelation anchored amorphous regions of the protein chain, and increasing stiffness. These differences are highlighted and validated through large amplitude oscillatory strain near physiologic levels, after incorporation of material characterization at molecular and micron length scales.

Genipin crosslinking of cartilage enhances resistance to biochemical degradation and mechanical wear.

Collagen crosslinking enhances many beneficial properties of articular cartilage, including resistance to chemical degradation and mechanical wear, but many crosslinking agents are cytotoxic. The purpose of this study was to evaluate the effectiveness of genipin, a crosslinking agent with favorable biocompatibility and cytotoxicity, as a potential treatment to prevent the degradation and wear of articular cartilage. First, the impact of genipin concentration and treatment duration on the viscoelastic properties of bovine articular cartilage was quantified. Next, two short-term (15 min) genipin crosslinking treatments were chosen, and the change in collagenase digestion, cartilage wear, and the friction coefficient of the tissue with these treatments was measured. Finally, chondrocyte viability after exposure to these genipin treatments was assessed. Genipin treatment increased the stiffness of healthy, intact cartilage in a dose-dependent manner. The 15-min crosslinking treatments improved cartilage's resistance to both chemical degradation, particularly at the articular surface, and to damage due to mechanical wear. These enhancements were achieved without sacrificing the low coefficient of friction of the tissue and at a genipin dose that preserved chondrocyte viability. The results of this study suggest that collagen crosslinking via genipin may be a promising preventative treatment to slow the degradation of cartilage.

Tailoring material properties of cardiac matrix hydrogels to induce endothelial differentiation of human mesenchymal stem cells.

Cardiac matrix hydrogel has shown great promise as an injectable biomaterial due to the possession of cardiac-specific extracellular matrix composition. A cardiac matrix hydrogel facilitating neovascularization will further improve its therapeutic outcomes in cardiac repair. In this study, we explored the feasibility of tailoring material properties of cardiac matrix hydrogels using a natural compound, genipin, to promote endothelial differentiation of stem cells. Our results demonstrated that the genipin cross-linking could increase the mechanical properties of the cardiac matrix hydrogel to a stiffness range promoting endothelial differentiation of human mesenchymal stem cells (hMSCs). It also decreased the swelling ratio and prolonged degradation without altering gelation time. Human mesenchymal stem cells cultured on the genipin cross-linked cardiac matrix hydrogels showed great viability. After 1 day culture, hMSCs demonstrated down-regulation of early endothelial marker expression and up-regulation of mature endothelial marker expression. Especially for 1 mM genipin cross-linked cardiac matrix hydrogels, hMSCs showed particularly significant expression of mature endothelial cell marker vWF. These attractive results indicate the potential of using genipin cross-linked cardiac matrix hydrogels to promote rapid vascularization for cardiac infarction treatment through minimally invasive therapy.

In situ forming chitosan-based hydrogel as a lung sealant for biological lung volume reduction

Biological lung volume reduction (BLVR) using lung sealant has received more attention recently as a new non-surgical approach to emphysema treatment. Many tissue sealants have been studied but only a few have been proposed for BLVR. In this work, we prepared in situ forming chitosan-based hydrogels (CSG) using covalent cross-linking of chitosan and genipin in the cooperation of ionic interaction between chitosan and sodium orthophosphate hydrate (Na3PO4·12H2O) and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy and rheological methods. CSG showed short gelation time (8min), high swelling ratio (>100%) and non-toxicity (3T3 mouse fibroblast cell viability >80%) under physiological conditions. The application of lung sealant for BLVR was tested in a Chinese dog and evaluated by chest computed tomography. After 3 weeks of the installation of CSG in bronchopulmonary segment, the gel formation was detected at a localized region of bronchi and the local atelectasis occurred. Our findings indicate that this chitosan-based hydrogel is a promising new candidate for use as a lung sealant for BLVR.

Injectable in situ forming chitosan-based hydrogels for curcumin delivery

In this paper, a series of injectable in situ forming chitosan-based hydrogels were prepared by chemical crosslinking of chitosan and genipin with the cooperation of ionic bonds between chitosan and sodium salts at room temperature. Four hydrogels (A, B, C, and D) were obtained by mixing chitosan, genipin and a sodium salt of trisodium phosphate (Na3PO4·12H2O), sodium sulfate (Na2SO4), sodium sulfite (Na2SO3), or sodium bicarbonate (NaHCO3) and examined for their characteristics, morphology, and rheological properties. Their cell viability assays exhibited low toxicity and the localized in situ gel formation was detected after subcutaneous injections in rat. Curcumin which possesses many pharmaceutical potentials but has low bioavailability, was chosen as a drug model. In vitro curcumin release profiles exhibit sustained release properties with initial burst release for all hydrogels with about 3 to 6 times higher cumulative release than other gel controls. The results of this study demonstrate that our hydrogels have a potential as local curcumin carriers.