Benzeneboronic-alginate/quaternized chitosan-catechol powder with rapid self-gelation, wet adhesion, biodegradation and antibacterial activity for non-compressible hemorrhage control.

Although hemostatic powders have excellent adaptability for irregular and inaccessible wounds, their hemostasis for continuous bleeding or bleeding wounds of non-compressible organs remains a critical challenge. Herein, a series of benzeneboronic acid-modified sodium alginate/catechol-modified quaternized chitosan (SA-BA/QCS-C, SBQCC) powders is developed by borate ester crosslinking for non-compressible hemorrhage control. SBQCC powders possess remarkable tissue adhesion, rapid self-gelation, good cytocompatibility and antibacterial activity against S. aureus and E. coil. The blood coagulation assays show that SBQCC powders display excellent blood clotting ability due to the synergistic effect of SA-BA and QCS-C. The SBQCC2 powder with the SA-BA to QCS-C mass ratio of 5 to 3 has the greatest effect on the blood-clotting rate. Upon depositing SBQCC2 powder to bleeding wounds of rabbit liver, the powder can absorb a large amount of blood and form a stable hydrogel physical barrier at the bleeding wounds in situ to achieve non-pressing rapid hemostasis. The SBQCC2 powder also has good biocompatibility and can be degraded in vivo. Altogether, the SBQCC powders can be a promising candidate for rapid hemostasis, and these findings may provide a new perspective for improving the hemostatic efficiency of the hemostatic powder in biomedical fields.

Combination of natural polyanions and polycations based on interfacial complexation for multi-functionalization of wound dressings.

Multi-functionalization of wound dressings with natural polymers is meaningful and remains a challenge. The combination of natural polyanions and polycations appears to be a promising strategy. Still, its performances based on current layer-by-layer self-assembly or homogeneous complexation are mutable and limited. Herein, Ca2+-incorporated carboxymethyl cellulose (Ca/Na-CMC) and hydroxypropyltrimethyl ammonium chloride chitosan (HACC) are adopted as the model polyanion and polycation, respectively, to develop multi-functionalized dressings based on interfacial complexation. The dressings exhibit a multilayer structure composed of a polyanion layer (Ca/Na-CMC) for hemostasis and promotion of cell proliferation, a formed polyelectrolyte complex (PEC) layer for structural stability, and a polycation layer (HACC) for antibiosis. Compared to the dressing based on homogeneous complexation, the multilayer dressings show stronger moisture penetrability (around 1,150 g/m2/24 h), higher hemostatic activity, and higher antibacterial rate (up to 100%) and promoted effect on cell proliferation. An in vivo evaluation using a rat full-thickness skin defect model reveals that the multilayer dressings can accelerate wound healing in 2 weeks. Overall, owing to interfacial complexation resulting in separate layers, the performances of polyanions and polycations after combination are more predictable, and their biological functions can be effectively preserved. These findings not only support the extensive application of multilayer dressings but also offer an alternative strategy for multi-functionalizing wound dressings with natural polyanions and polycations.

Acid Leaching Vermiculite: A Multi-Functional Solid Catalyst with a Strongly Electrostatic Field and Brönsted Acid for Depolymerization of Cellulose in Water.

Vermiculite is a natural mineral. In this study, vermiculite and acid-activated vermiculite was used as a solid acid catalyst for the hydrolysis of cellulose in water. The catalysts were characterized by XRD, FT-IR, and BET. The effects of time, temperature, mass ratio and water amount on the reaction were investigated in the batch reactor. The results showed that the highest total reducing sugars (TRS) yield of 40.1% could be obtained on the vermiculite activated by 35 (wt)% H2SO4 with the mass ratio of catalyst to cellulose of 0.18 and water to cellulose of 16 at 478 K for 3.5 h. The acid-activated vermiculite was a stable catalyst through calcination at 628 K and the yield of TRS decreased to 36.2% after three times reuse. The results showed that the crystal structure of vermiculite was destroyed and the surface -OH groups increased after the acid treatment. However, the synergistic effect of a strongly electrostatic polarization and Brönsted acid was responsible for the efficient conversion of cellulose. The mechanism of cellulose hydrolysis on the acid-activated vermiculite was suggested. This work provides a promising strategy to design an efficient solid catalyst for the cellulose hydrolysis, and expands the use of vermiculite in a new field.

Freeform optical surface design in an off-axis reflective imaging system by a double seed curve extension algorithm.

A double seed curve extension (DSCE) method is proposed to design a freeform surface directly in an off-axis reflective imaging system. Compared with the basic seed curve extension (SCE) method, the DSCE can effectively reduce the error of freeform surface construction and improve the imaging quality of the off-axis reflective imaging system. In addition, the method can be employed to design an off-axis reflective imaging system consisting of multiple freeform surfaces with several virtual image points set in advance. In order to verify the DSCE method, three examples are given. One is the off-axis freeform one-mirror system, one is a compact off-axis three-mirror imaging system with two freeform surfaces, and the other is an off-axis reflective system with three freeform surfaces. The modulation transfer function (MTF) of the one-mirror system is greater than 0.9 at 20 lp/mm, which is close to the diffraction limit. The average of the sagittal and tangential MTFs of the second system designed by the SCE and DSCE methods are 0.26 and 0.74 at spatial frequency of 20 lp/mm, respectively. And the MTF of the last system designed by the DSCE method is greater than 0.9 at 20 lp/mm, which is better than that of the SCE method.

Absorbable nanocomposites composed of mesoporous bioglass nanoparticles and polyelectrolyte complexes for surgical hemorrhage control.

Absorbable polyelectrolyte complexes-based hemostats are promising for controlling hemorrhage in iatrogenic injuries during surgery, whereas their hemostatic efficacy and other performances require further improvement for clinical application. Herein, spherical mesoporous bioglass nanoparticles (mBGN) were fabricated, and mBGN-polyelectrolyte complexes (composed of carboxymethyl starch and chitosan oligosaccharide) nanocomposites (BGN/PEC) with different mBGN contents were prepared via in situ coprecipitation followed by lyophilization. The effect of various mBGN content (10 and 20 wt%) on morphology, zeta potential, water absorption, degradation behavior and ion release were systematically evaluated. The in vitro degradability was dramatically promoted and a more neutral environment was achieved with the incorporation of mBGN, which is preferable for surgical applications. The in vitro coagulation test with whole blood demonstrated that the incorporation of mBGN facilitated blood clotting process. The plasma coagulation evaluation indicated that BGN/PEC had increased capability to accelerate coagulation cascade via the intrinsic pathway than that of the PEC, while have inapparent influence on the extrinsic and common pathway. The in vivo hemostatic evaluation in a rabbit hepatic hemorrhage model revealed that BGN/PEC with 10 wt% mBGN (10BGN/PEC) treatment group had the lowest blood loss, although its hemostatic time is close to that of 20BGN/PEC treatment group. The cytocompatibility evaluation with MC3T3-L1 fibroblasts indicated that 10BGN/PEC induced a ~25% increase of cell viability compared to the PEC at days 4 and 7, indicating improved biocompatibility. These findings support the promising application of absorbable BGN/PEC with optimized mBGN content as internal hemostats and present a platform for further development of PEC-based hemostats.

Simonkolleite Coating on Poly(Amino Acids) to Improve Osteogenesis and Suppress Osteoclast Formation in Vitro.

Zinc can enhance osteoblastic bone formation and stimulate osteogenic differentiation, suppress the differentiation of osteoclast precursor cells into osteoclasts, and inhibit pathogenic bacterial growth in a dose-dependent manner. In this study, simonkolleite, as a novel zinc resource, was coated on poly (amino acids) (PAA) via suspending PAA powder in different concentrations of zinc chloride (ZnCl2) solution, and the simonkolleite-coated PAA (Zn-PAA) was characterized by SEM, XRD, FT-IR and XPS. Zinc ions were continuously released from the coating, and the release behavior was dependent on both the concentration of the ZnCl2 immersing solution and the type of soak solutions (SBF, PBS and DMEM). The Zn-PAA was cultured with mouse bone marrow stem cells (BMSCs) through TranswellTM plates, and the results indicated that the relative cell viability, alkaline phosphatase (ALP) activity and mineralization of BMSCs were significantly higher with Zn-PAA as compared to PAA. Moreover, the Zn-PAA was cultured with RAW264.7 cells, and the results suggested an inhibiting effect of Zn-PAA on the cell differentiation into osteoclasts. In addition, Zn-PAA exhibited an antibacterial activity against both S. aureus and E. coli. These findings suggest that simonkolleite coating with certain contents could promote osteogenesis, suppress osteoclast formation and inhibit bacteria, indicating a novel way of enhancing the functionality of synthetic bone graft material and identifying the underline principles for designing zinc-containing bone grafts.

Developing novel Ca-zeolite/poly(amino acid) composites with hemostatic activity for bone substitute applications.

The novel Ca-zeolite/poly(amino acid) (CaY/PAA) composites for bone substitute applications with hemostatic activity were prepared using the in situ melting polymerization method. In this study, Ca-zeolite (CaY) loaded with Ca2+ was obtained from Y-type zeolite (NaY) by ion-exchange method. The properties of the CaY/PAA composites and PAA, including composition, structure, compressive strength, in vitro degradability in phosphate-buffered solution (PBS), bioactivity, cytocompatibility and in vitro coagulation tests were characterized and investigated. The results showed that compressive strength of the CaY/PAA composites ranged from 145 to 186 MPa, demonstrating sufficient mechanical strength for load-bearing bone substitute. After soaking in PBS for 16 weeks, the weight loss of 25CaY/PAA and 50CaY/PAA were 4.1 and 1.6 wt%, respectively, and the pH values for CaY/PAA composites increased to about 8.0 in 2 weeks and then gradually stabilized around 7.4, indicating good stability in PBS. Scanning electron microscope and energy dispersive spectrometer results showed that the composites were bioactive and new apatite layers attached on their surfaces. Mesenchymal stem cells (MSCs) exhibited high-proliferation in the extract solution of the CaY/PAA composites and were well spread on the surfaces of the composites. Cells on the CaY/PAA composite groups showed higher alkaline phosphatase (ALP) activity indicating the potential to promote cell differentiation. The in vitro coagulation tests showed that CaY/PAA composites have shorter clotting time and better performance of promoting blood coagulation than other samples, presenting improved hemostatic activity. In summary, the results demonstrated that the CaY/PAA composites had good mechanical strength, stability, bioactivity, cytocompatibility and hemostatic activity for bone substitute applications.

Evaluation of absorbable hemostatic agents of polyelectrolyte complexes using carboxymethyl starch and chitosan oligosaccharide both in vitro and in vivo.

Absorbable hemostatic agents with a high hemostatic efficacy play an important role in surgical and severely traumatic hemostasis. In the present study, by applying polyelectrolyte assembly, polyelectrolyte complexes (PECs), using carboxymethyl starch (CMS) and chitosan oligosaccharide (COS), with controllable physicochemical properties were prepared and optimized for hemorrhage control. Particle size, zeta potential, morphology and water absorption of the PECs with different CMS/COS ratios were systematically evaluated. The results of in vitro degradation in PBS suggested that CMS/COS PECs were degradable and their degradation rates, which decreased with the increase of the COS content, were suitable for absorbable hemostatic agents. The in vivo hemostatic efficacy of the PECs with 10 wt% COS content (PEC 10), which was evaluated in a rabbit hepatic hemorrhage model, was better than CMS but decreased with the increase of the COS content. The plasma coagulation evaluation revealed that the PECs could significantly activate and accelerate the coagulation cascade through both the intrinsic and extrinsic pathways but could not directly affect the common pathway. CMS/COS PECs also showed antimicrobial activity against S. aureus, which enhanced with the increase of the COS content, but failed against E. coli. Moreover, PEC 10 displayed excellent cytocompatibility with MC3T3-L1 and good tissue compatibility in a rabbit liver model. These findings not only suggest that CMS/COS PECs with a suitable COS content were promising absorbable hemostatic agents for internal use but they are also useful to understand the underlying principles for designing PEC based hemostatic agents.

[Comparative studies on the material performances of natural bone-like apatite from different bone sources].

The compressive strength of the original bone tissue was tested, based on the raw human thigh bone, bovine bone, pig bone and goat bone. The four different bone-like apatites were prepared by calcining the raw bones at 800 degrees C for 8 hours to remove organic components. The comparison of composition and structure of bone-like apatite from different bone sources was carried out with a composition and structure test. The results indicated that the compressive strength of goat bone was similar to that of human thigh bone, reached (135.00 +/- 7.84) MPa; Infrared spectrum (IR), X-ray diffraction (XRD) analysis results showed that the bone-like apatite from goat bone was much closer to the structure and phase composition of bone-like apatite of human bones. Inductively Coupled Plasma (ICP) test results showed that the content of trace elements of bone-like apatite from goat bone was closer to that of apatite of human bone. Energy Dispersive Spectrometer (EDS) results showed that the Ca/P value of bone-like apatite from goat bone was also close to that of human bone, ranged to 1.73 +/- 0.033. Scanning electron microscopy (SEM) patterns indicated that the macrographs of the apatite from human bone and that of goat bone were much similar to each other. Considering all the results above, it could be concluded that the goat bone-like apatite is much similar to that of human bone. It can be used as a potential natural bioceramic material in terms of material properties.

Preparation and properties of BSA-loaded microspheres based on multi-(amino acid) copolymer for protein delivery.

A multi-(amino acid) copolymer (MAC) based on ω-aminocaproic acid, γ-aminobutyric acid, L-alanine, L-lysine, L-glutamate, and hydroxyproline was synthetized, and MAC microspheres encapsulating bovine serum albumin (BSA) were prepared by a double-emulsion solvent extraction method. The experimental results show that various preparation parameters including surfactant ratio of Tween 80 to Span 80, surfactant concentration, benzyl alcohol in the external water phase, and polymer concentration had obvious effects on the particle size, morphology, and encapsulation efficiency of the BSA-loaded microspheres. The sizes of BSA-loaded microspheres ranged from 60.2 µm to 79.7 µm, showing different degrees of porous structure. The encapsulation efficiency of BSA-loaded microspheres also ranged from 38.8% to 50.8%. BSA release from microspheres showed the classic biphasic profile, which was governed by diffusion and polymer erosion. The initial burst release of BSA from microspheres at the first week followed by constant slow release for the next 7 weeks were observed. BSA-loaded microspheres could degrade gradually in phosphate buffered saline buffer with pH value maintained at around 7.1 during 8 weeks incubation, suggesting that microsphere degradation did not cause a dramatic pH drop in phosphate buffered saline buffer because no acidic degradation products were released from the microspheres. Therefore, the MAC microspheres might have great potential as carriers for protein delivery.