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Self-sealing hyaluronic acid (HA)-coated self-sealing 30-gauge needles exhibiting instant leakage prevention of intravitreal humor and injected drug were developed in this study. Ninety New Zealand rabbits were used in this study. We assessed dye regurgitation in intravitreal ICG dye injections using HA-coated needles (HA needle group) and conventional needles (control group). Vitreous humor levels of anti-vascular endothelial growth factor (VEGF) were compared between groups one, three, and seven days after intravitreal bevacizumab (0.016 mL) injections. Expression levels of inflammatory cytokines in the aqueous humor and vitreous humor, including prostaglandin E2 (PGE2), interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-4, IL-6, IL-17, and IL-8, were compared between HA needle, control, and normal (in which intravitreal injection was not performed) groups following 12 intravitreal injections over a period of one week. In the HA needle group, HA remained at the injection site and blocked the hole after intravitreal injection. Dye regurgitation occurred significantly less frequently in the HA needle group (16.7%) than the control group (55.6%) after intravitreal ICG dye injection. Meanwhile, vitreous anti-VEGF levels were markedly higher in the HA needle group than the control group one and three days after intravitreal bevacizumab injections. After 12 intravitreal injections, expression levels of aqueous and vitreous IL-8 significantly increased in the control group compared to the HA needle and normal groups. Conversely, there were no significant differences in the expression of the other seven cytokines among the three groups. Intravitreal injections using HA-coated self-sealing 30-gauge needles can block the outflow of vitreous humor and drugs through the needle passage.

Marine mussels secrete adhesive proteins to attach to solid surfaces. These proteins contain phenolic and basic amino acids exhibiting wet adhesion properties. This study used a mussel-inspired hemostatic polymer, chitosan-catechol, to treat gastrointestinal bleeding caused by endoscopic mucosal resection in a heparinized porcine model. We aimed to evaluate the hemostatic efficacy and short-term safety of this wet adhesive chitosan-catechol. We used 15 heparinized pigs. Four iatrogenic bleeding ulcers classified as Forrest Ib were created in each pig using an endoscopic mucosal resection method. One ulcer in each pig was untreated as a negative control (no-treatment group). The other three ulcers were treated with gauze (gauze group), argon plasma coagulation (APC group), and chitosan-catechol hemostatic agent (CHI-C group) each. The pigs were sacrificed on Days 1, 5, and 10, and histological examination was performed (n = 5 per day). Rapid hemostasis observed at 2 min after bleeding was 93.3% (14/15) in the CHI-C group, 6.7% (1/15) in the no-treatment group, 13.3% (2/15) in the gauze group, and 86.7% (13/15) in the APC group. No re-bleeding was observed in the CHI-C group during the entire study period. However, a few re-bleeding cases were observed on Day 1 in the no-treatment, gauze, and APC groups and on Day 5 in the gauze and APC groups. On histological analysis, the CHI-C group showed the best tissue healing among the four test groups. Considering the results, chitosan-catechol is an effective hemostatic material with reduced re-bleeding and improved healing.

Mussel-inspired adhesion chemistry provides a useful alternative to the use of fibrin glues., Since the first report of underwater adhesive proteins of marine mussels in 1981, numerous studies have reported mussel-inspired synthetic adhesive polymers. However, none of them have developed up to human-level translational studies. Here, we report a sticky polysaccharide that effectively promotes hemostasis from animal bleeding models to first-in-human hepatectomy. We found that the hemostatic material instantly generates a barrier layer that seals hemorrhaging sites. The barrier is created within a few seconds by in situ interactions with abundant plasma proteins. Therefore, as long as patient blood contains proper levels of plasma proteins, hemostasis should always occur even in coagulopathic conditions. To date, insufficient tools have been developed to arrest coagulopathic bleedings originated from genetic disorders, chronic diseases, or surgical settings such as organ transplantations. Mussel-inspired adhesion chemistry described here provides a useful alternative to the use of fibrin glues up to a human-level biomedical application.

Purpose InnoSEAL Plus is an adhesive, coagulant-free hemostatic material that mimics the adhesion mechanism of marine mussels. This study reports on the safety and efficacy of InnoSEAL Plus for patients with hemorrhage after hepatectomy despite first-line hemostasis treatments. Methods This is a multicenter, prospective, single-blinded, randomized clinical trial involving 96 hepatectomy patients. TachoSil was used as a comparator group. Three-minute and 10-minute hemostatic success rates were monitored. Rebleeding rates were also observed. Safety was assessed by recording all novel undesirable symptoms. Results InnoSEAL Plus showed a 3-minute hemostasis rate of 100%, while TachoSil had a rate of 98.0% (48 of 49 patients), demonstrating that the 2 had similar hemostatic efficacies. The difference in efficacy between the test and comparator group was 2.04%, and the lower limit of the one-sided 97.5% confidence interval was −1.92%; as this is greater than the noninferiority limit of −23.9%, the 2 treatments were equivalent. Meanwhile, the 10-minute hemostatic success rate was the same in both groups (100%). No rebleeding occurred in either group. In the safety evaluation, 89 patients experienced adverse events (45 in the test group and 44 in the comparator group). The difference between the 2 groups was not significant. No death occurred after application of the test or comparator group product. Conclusion Given that InnoSEAL Plus is a coagulation factor-free product, the hemostasis results are encouraging, especially considering that TachoSil contains a coagulation factor. InnoSEAL Plus was found to be a safe and effective hemostatic material for control of bleeding in hepatectomy patients.

Organically modified silicates incorporated with calcium salts produce novel, bioactive materials, which bond directly to living bone, because after exposure to a physical environment, calcium silicates have a high hydroxyapatite-deposit potential. In this study, transparent, monolithic, bi-structured hybrids were prepared using a sol–gel process for the CaO–SiO2-PTMO system. To establish the bi-structure, two types of sols were prepared: a polymer-rich sol that had a starting composition of PTMO/TEOS in an 80/20 mass ratio and a ceramic-rich sol that had a starting composition of TEOS/Ca(NO3)2 in a 1/0.3 molar ratio. The bi-structured hybrid was synthesized using a gelation process, where the ceramic-rich sol was placed on the polymer-rich wet gel. An interfacial structure with tight binding was established between the two gels that had the potential to form calcium phosphate within a period of 6 h on the bi-structured hybrid. This process led to the successful synthesis of a bi-structured hybrid with a high potential for bone-bonding property, which was also flexible.

The osteoconduction potential of artificial materials is usually evaluated in vitro by apatite formation in a simulated body fluid (SBF) proposed by Kokubo and his colleagues. This paper reports the compositional dependence of apatite formation on organic-inorganic hybrids in the CaO-SiO(2)-PO(5/2)-poly(tetramethylene oxide) system, initiated from tetraethoxysilane (TEOS), triethyl phosphate (OP(OEt)(3)), calcium chloride (CaCl(2)) and poly(tetramethylene oxide)(PTMO) modified with alkoxysilane. Formation of an apatite layer was observed on the surface of the organic-inorganic hybrids with molar ratios of TEOS/OP(OEt)(3) ranging from 100/0 to 20/80. The rate of apatite formation remarkably decreased when the hybrids were synthesized with TEOS/OP(OEt)(3) ratios of 40/60 or less. Hybrids without TEOS showed no apatite formation in SBF for up to 14 days. Addition of small amounts of OP(OEt)(3) to TEOS in the hybrids led to the high dissolution of calcium and silicate, while addition of large amounts of OP(OEt)(3) decreased the dissolution of calcium and silicate ions and resulted in reduced apatite formation regardless of the dissolution of phosphate ions from the hybrids.

Bioactive organic-inorganic hybrids can be used as biomaterials for bone substitution because they exhibit osteoconduction and other functions due to their organic components, such as flexibility and bioabsorbability. In this study, we synthesized uniform organic-inorganic hybrids from triethoxysilane-functionalized poly (tetramethylene oxide) (Si-PTMO), tetraethoxysilane (TEOS) and calcium chloride (CaCl 2 ) via the sol-gel process. The starting composition of Si-PTMO/TEOS molar had a weight ratio ranging from 20/80 to 90/10. The CaCl 2 concentration was kept constant at a CaCl 2 /TEOS molar ratio of 0.15. Uniform and transparent hybrids were obtained with a Si-PTMO/TEOS compositional range from 20/80 to 90/10. The potential bioactivity was evaluated by determining the formation of a bone-like apatite layer in simulated body fluid (SBF). Formation of a bone-like apatite layer was observed on the surface of the organic-inorganic hybrids when they were prepared from starting compositions of Si-PTMO/TEOS with weight ratios ranging from 20/80 to 50/50. An appreciable quantity of the calcium silicate is required to produce bioactive organic-inorganic hybrids.

Hydrogels able to form a bone-like hydroxyapatite (HAp) layer in the body environment are attractive materials as scaffolds for tissue engineering because they show osteoconductivity, i.e. bone-bonding property. In the present study, we synthesized hydrogels from sodium carboxymethylcellulose (sCMC), a water soluble polymer, through modification with a cross-linking agent, either ethylenediamine (EDA) or 3-aminopropyltriethoxysilane (APTES), followed by treatment with an aqueous solution containing calcium chloride aqueous solution. Formation of the bone-like HAp on the hydrogels was evaluated after immersion in a simulated body fluid (SBF). Hydrogels modified with the cross-linking agents EDA or APTES, and treated with 0.1 mol/dm3 of calcium chloride aqueous solution, formed a bone-like HAp layer on their surfaces after immersion in SBF for 3 days. Modification of organic polymers rich in carboxyl groups with APTES and CaCl2 offers a new method to produce biomaterials with greater potential for forming HAp, which provides high affinity to living bone because the incorporation of silanol groups confers the high ability to induce HAp formation.