Corrigendum: A minimally manipulated preservation and virus inactivation method for amnion/chorion.

[This corrects the article DOI: 10.3389/fbioe.2022.952498.].

A minimally manipulated preservation and virus inactivation method for amnion/chorion.

Allogeneic amnion tissues have been widely used in tissue repair and regeneration, especially a remarkable trend of clinical uses in chronic wound repair. The virus inactivation procedures are necessary and required to be verified for the clinical use and approval of biological products. Cobalt-60 (Co-60) or electron-beam (e-beam) is the common procedure for virus and bacterial reduction, but the excessive dose of irradiation was reported to be harmful to biological products. Herein, we present a riboflavin (RB)-ultraviolet light (UV) method for virus inactivation of amnion and chorion tissues. We used the standard in vitro limiting dilution assay to test the viral reduction capacity of the RB-UV method on amnion or chorion tissues loaded with four types of model viruses. We found RB-UV was a very effective procedure for inactivating viruses of amnion and chorion tissues, which could be used as a complementary method to Co-60 irradiation. In addition, we also screened the washing solutions and drying methods for the retention of growth factors.

"PP-type" self-assembling peptides with superior rheological properties.

The ionic-complementary self-assembling peptides discovered by Zhang Shuguang have solution-to-gel (sol-gel) transition capacity and one such peptide RADA16 has been commercialized into hemostatic agents. However, their sol-gel transition ability was not obvious because the peptide aqueous solution with a concentration greater than 1% w/v appeared to be thick and viscous. The current report describes PP-type self-assembling peptides. In addition to the ionic-complementary sequence, they have prolines at both ends of the sequence. This feature has led to better solubility, lower viscosity of the peptide solution, and simplified synthesis and purification processes while maintaining the great gelling performance of the ionic-complementary peptides. The PP-type peptides self-assembled into a well-organized nanofiber scaffold as shown by TEM. Among the PP-type peptides, the PRVDP9 sequence peptide was tested as a hemostatic agent and a mucosal elevating agent. The results were comparable to the classic RADA16. The PP-type self-assembling peptides have superior sol-gel transition ability. Therefore, it is predicted that they will be more suitable to be transported through catheters or endoscopes and have higher commercialization potential as compared with the classic self-assembling peptide sequences.

[Copolymer of 2-hydroxyethyl methacrylate for cerebral arteriovenous malformation: an experimental study].

OBJECTIVE: To investigate the feasibility of using methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA) to embolize cerebral arteriovenous malformations (AVM). METHODS: Methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA) in the ratio of 9:1 were solved in 16% alcohol so as to make a kind of copolymer (CoHEMA). 12 g glass beads 2 mm in diameter were put into a container so as to construct an in vitro model of AVM. The container was connected with a normal saline bottle via microcatheter. CoHEMA, as embolized, was injected through the microcatheter and the diffusion of CoHEMA was observed till the water flow was stopped. CoHEMA was injected through microcatheter into the pharyngeal ascending arteries near the rete mirabile (RMB) tissue, similar to the human AVM, under digital subtraction angiography until satisfactory embolization was obtained, totally 9 RMB tissues in 7 pigs. Five pigs were injected with normal saline as controls. The pigs were killed 2 days, 2 weeks, and 6 months after embolization respectively and the bilateral RMB tissues were taken out to undergo pathological examination. RESULTS: Nine AVM models in vitro were constructed with the copolymer dispersed symmetrically among the glass beads and stopped the fluid across the model effectively. No copolymer adhered to the wall of microcatheter. Nine RMB tissues of 6 pigs were embolized by using CoHEMA. Six of the seven pigs survived the procedure except one died of too fast injection of copolymer in the primary stage. Follow-up angiography was performed in four pigs and found that no recanalization occurred and the copolymer was diffused in the vessels 80-150 microm in diameter. In the specimens obtained 2 days after embolization, neutrophilic granulocytes scattered surrounding the copolymer, suggesting minor inflammatory reaction. In the specimens obtained 2 weeks after embolization no vessel wall damage and morphological change were found except minor inflammatory reaction inside the vessels and surrounding tissues. In the specimens obtained 2 to 6 months after embolization hyperplasia of connective tissue, minor or mediate chronic inflammatory reaction, and giant cell reaction inside the vessels and surrounding tissues. CONCLUSION: With low viscosity, better biocompatibility, and embolic instability, and easy to be injected through delivery microcatheter, CoHEMA is an excellent non-adhesive embolic material and can be used in embolic treatment of cerebral AVM.

Technical feasibility and histopathologic studies of poly (N-isopropylacrylamide) as a non-adhesive embolic agent in swine rete mirabile.

BACKGROUND: Non-adhesive liquid embolic agents are increasingly gaining importance in the embolization of cerebral arteriovenous malformations (AVMs). We investigated the use of poly (N-isopropylacrylamide) (PNIPAM) as a non-adhesive embolic agent in swine rete mirabile. METHODS: The PNIPAM hydrogel was mixed with iohexol and embolization was performed in swine rete mirabile in 30 animals. The microcatheter was examined after embolization. Follow-up angiography was performed for embolic efficacy after embolization. Embolized retia were examined histopathologically, and the alterations of inside rete and surrounding tissue were observed. RESULTS: The copolymer hydrogel was used for rete embolization in 30 swine, 28 swine survived the procedure, 2 swine died, 1 swine died of cerebrum infarction and the other died of embolic agent reflux into the occipital artery. The inside wall of the microcatheter was smooth, without copolymer adhering to it. Follow-up angiography was performed in 22 swine, there was no rete recanalization in 20 swine and partial rete recanalization in 2 swine because of the trunk embolization of ascending pharyngeal arteries. Histopathologically, the copolymer was found diffused into vessels of 100 - 150 microm in diameter. In acute group, neutrophils scattered surrounding the copolymer and endothelial integrity was observed, without endothelial denuding and necrosis. In subacute and chronic groups, the copolymer was found inside retia, a few mononuclear cells and eosinocytes scattered inside and surrounding it. The muscular layer was loosened with most muscular nuclei degraded. CONCLUSION: Experimental rete embolization with PNIPAM, made radiopaque with iohexol, is technically feasible in swine. Because of its properties, PNIPAM has great potential as a therapeutic non-adhesive embolic agent.

A rapid temperature-responsive sol-gel reversible poly(N-isopropylacrylamide)-g-methylcellulose copolymer hydrogel.

Poly(N-isopropylacrylamide) (PNIPAAm) was grafted to methylcellulose (MC) with various feeding ratios using ammonium persulfate and N,N,N',N'-tetramethyl ethylene diamine as an initiator. FTIR results confirm the formation of PNIPAAm-g-MC copolymers. The temperature responsiveness of copolymer gels was investigated by turbidimetry, dynamic contact angle (DCA), differential scanning calorimetry and dynamic mechanical analysis (DMA). The results indicate that PNIPAAm-g-MC hydrogels are strongly temperature responsive. At lower contents of MC, the lower critical solution temperature (LCST) is decreased, whereas further increasing MC contents raises the LCSTs. It is observed that the phase transition of the hydrogels occurs reversibly within 1 min, and near body temperature, a rigid gel can be generated in a certain range of MC content. What is more, the incorporation of MC prevents the syneresis of copolymer hydrogel. DMA measurement reveals that the storage moduli (E') of the gels increase upon increasing MC contents, and moreover the values of E' go up markedly above LCST. The copolymer hydrogels hold a promise as a blood vessel barrier by tuning gelation temperature, gelation time and mechanical strength.