A Biosurfactant-containing TSD Strategy to Modify Bovine Pericardial Bioprosthetic Valves for Anticalcification

Bioprosthetic heart valves(BHVs)are important for transcatheter valve replacement.Current commercial BHVs on the market are basically porcine or bovine pericardium(BP)crosslinked with glutaraldehyde(GA).Simply applying GA to BHVs can enhance mechanical stability,but cannot alleviate in vivo calcification.In this work,we developed a two-step decellularization(TSD)strategy to modify this biomacromolecular network,in which BP was post-treated,as the second step of decellularization,with a mild biosurfactant n-dodecyl-β-D-maltoside in a mixture of isopropanol and phosphate-buffered saline after the first step of traditional decellularization and GA cross-linking.The TSD-treated BP exhibited not only low cytotoxicity and excellent mechanical properties in vitro,but also low immune responses and significant anticalcification in vivo.After 60 days of subcutaneous implantation in the back of Wistar rats,the calcium content was,as quantified with an inductively coupled plasma optical emission spectrometer,only 1.1µg/mg compared to 138.6µg/mg in the control group without the post-treatment.In addition,collagen fibrils were observed with field emitting scanning electron microscopy(SEM),and the morphology and composition of the calcified sites resulting from in vivo biomineralization were studied with SEM with energy dispersive spectroscopy and also X-ray diffraction.This study proposes a facile yet effective anticalcification strategy for the modification of the bovine pericardial bioprosthetic heart valve,a natural biomacromolecular network.

Stride Strategy to Enable a Quasi-ergodic Search of Reaction Pathways Demonstrated by Ring-opening Polymerization of Cyclic Esters

Coordination-insertion ring-opening polymerization(ROP)of cyclic esters is an industrial way to synthesize polyesters,which are widely applied in biomedical and environment-benign fields.However,the rate-determining transition state(TS)identified by the conventional reaction pathways(pathway A and pathway B)presented in the literature did not well describe the structure-reactivity relationship.The misidentification of the rate-determining TS might arise from the less ergodicity in the search of reaction pathways.Herein,we suggested a stride strategy based on the insight that even a partial double bond is rotatable at the catalysis temperature.As a result,we revealed a new reaction pathway,pathway C with a torsion transition state TSC2,by density functional theory(DFT).We also carried out kinetic experiments of ROP of D-lactide(D-LA),L-lactide(L-LA),ε-caprolactone(CL),andδ-valerolactone(VL),using poly(ethylene glycol)as the initiator and stannous octoate as the catalyst.The excellent linearity between the calculated free energy barriers and logarithms of the experimental kinetic constants of the two kinds of lactide and lactone monomers,was established,validating the quasi-ergodic search of reaction pathways and the scaling predicted by transition state theory.The linearity was highly predictive for the other lactide and lactone monomers,demonstrated by glycolide(GA)and trimethylene urethane(TU).

Accelerated Cutaneous Wound Healing Using an Injectable Teicoplanin-loaded PLGA-PEG-PLGA Thermogel Dressing

Bacterial infection is a very troublesome issue in wound treatment, which stimulates exudate formation and severely delays the healing process. Herein, a thermogelling dressing system composed of two triblock copolymers of poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid-co-glycolic acid)(PLGA-PEG-PLGA) with different block lengths was developed to deliver teicoplanin(TPN), a glycopeptide antibiotic, for cutaneous wound repair. The TPN-loaded thermogel was a free-flowing sol at room temperature and formed a semi-solid gel at physiological temperature. In vitro studies demonstrated that the TPN-loaded thermogel system exhibited desired tissue adhesiveness and realized the sustained release of TPN in a fast-followed-slow manner for over three weeks. Furthermore, a full-thickness excision wound model in Sprague-Dawley(SD) rats was constructed to assess the efficacy of TPNloaded thermogel formulation. Gross and histopathologic observations implied that treatment with the thermogel formulation reduced inflammation response, promoted disposition of collagen, enhanced angiogenesis, and accelerated wound closure and maturity of SD rats.The combination of the bioactivity of TPN and the acidic nature of the thermogel matrix was responsible for such an enhanced wound healing process. Consequently, the TPN-loaded PLGA-PEG-PLGA thermogel is a good candidate of wound dressing for full-thickness excision wound healing.

An Injectable Hydrogel with or without Drugs for Prevention of Epidural Scar Adhesion after Laminectomy in Rats

Epidural scarring occurs inevitably in the defect after spinal laminectomy, and thus how to prevent or reduce it becomes a challenging topic. In the present study, an injectable hydrogel and its dexamethasone （DEX）-loaded hydrogel systems were adopted to prevent epidural scarring in a postlaminectomy rat model. The hydrogel system composed of poly（D,L-lactic acid-co-glycolic acid）-poly（ethylene glycol）-poly（D,L-lactic acid-co-glycolic acid） （PLGA-PEG-PLGA） triblock copolymers was a free-flowing sol at room temperature, and spontaneously turned into a semi-solid gel at body temperature. A lumbar 3 total laminectomy was performed on Sprague Dawley （SD） rats, and the efficacy of the injectable hydrogel with or without drugs in preventing epidural scar formation was evaluated via the gross anatomical observation and histological examination at one month post-surgery. The results demonstrate that the use of hydrogel alone reduced epidural scarring significantly, whereas the efficacy of the DEX-loaded hydrogels presented an irregular dose-dependency of drug and even the inappropriate drug doses resulted in the negative results. Therefore, the present study confirms that the PLGA-PEG- PLGA hydrogel holds potential as a barrier device to decrease peridural scarring, and reveals that the sustained delivery of the steroid hormone DEX to prevent surgery-related adhesions in the laminectomy defect is complex. Moreover, our in vivo studies also remind the researchers to pay attention to the irregular dose-dependency of the hormone drugs.