An ultrathin poly(L-lactic acid) nanosheet as a burn wound dressing for protection against bacterial infection.

Burn wounds are highly susceptible to bacterial infection due to impairment of the skin's integrity. Therefore, prevention of bacterial colonization/infection in the wound is crucial for the management of burns, including partial-thickness burn injuries. Although partial-thickness burn injuries still retain the potential for reepithelialization, the complication of wound infection severely impairs the reepithelialization even in such superficial burn injuries. We recently developed a biocompatible nanosheet consisting of poly(L-lactic acid) (PLLA). The PLLA nanosheets have many useful and advantageous biological properties for their application as a wound dressing, such as sufficient flexibility, transparency, and adhesiveness. We herein investigated the suitability of the PLLA nanosheets as a wound dressing for partial-thickness burn wounds in mice. The PLLA nanosheets tightly adhered to the wound without any adhesive agents. Although wound infection with Pseudomonas aeruginosa in the controls significantly impaired reepithelialization of burn wounds, dressing with the PLLA nanosheet markedly protected against bacterial wound infection, thereby improving wound healing in the mice receiving partial-thickness burn injuries. The PLLA nanosheet also showed a potent barrier ability for protecting against bacterial penetration in vitro. The ultrathin PLLA nanosheet may be applied as a protective dressing to reduce environmental contamination of bacteria in a partial-thickness burn wound.

Free-Standing Biodegradable Poly(lactic acid) Nanosheet for Sealing Operations in Surgery.

A free-standing biodegradable nanosheet composed of poly(L-lactic acid) (PLLA) was shown to have excellent sealing efficacy for a gastric incision as a novel wound dressing material that did not require adhesive agents, and the PLLA nanosheet-induced wound repair showed neither scars nor tissue adhesion. This material may, therefore, be an ideal alternative to conventional tissue repairing procedures using suture/ligation in surgery.

Novel platelet substitutes: disk-shaped biodegradable nanosheets and their enhanced effects on platelet aggregation.

We have studied biocompatible spherical carriers carrying a dodecapeptide, HHLGGAKQAGDV (H12), on their surface as platelet substitutes. This peptide is a fibrinogen γ-chain carboxy-terminal sequence (γ400-411) and specifically recognizes the active form of glycoprotein IIb/IIIa on activated platelets. Our purpose is to assess the possibility of making a novel platelet substitute consisting of disk-shaped nanosheets having a large contact area for the targeting site, rather than conventional small contact area spherical carriers. The H12 peptide was conjugated to the surface of the free-standing nanosheets made of biodegradable poly(d,l-lactide-co-glycolide) (PLGA). These H12-PLGA nanosheets were fabricated onto 3 µm disk-shaped patterned hydrophobic octadecyl regions on a SiO(2) substrate. By way of comparison, spherical H12-PLGA microparticles with the same surface area and conjugation number of H12 were also prepared. The resulting H12-PLGA nanosheets specifically interacted with the activated platelets adhered on the collagen surface at twice the rate of the H12-PLGA microparticles under flow conditions, and showed platelet thrombus formation in a two-dimensional spreading manner. Thus, H12-PLGA nanosheets might be a suitable candidate novel platelet alternative substitute for infused human platelet concentrates for the treatment of bleeding in patients with severe thrombocytopenia.

Hepatitis B surface antigen incorporated in dissolvable microneedle array patch is antigenic and thermostable.

Alternatives to syringe-based administration are considered for vaccines. Intradermal vaccination with dissolvable microneedle arrays (MNA) appears promising in this respect, as an easy-to-use and painless method. In this work, we have developed an MNA patch (MNAP) made of hydroxyethyl starch (HES) and chondroitin sulphate (CS). In swines, hepatitis B surface antigen (HBsAg) formulated with the saponin QS-21 as adjuvant, both incorporated in HES-based MNAP, demonstrated the same level of immunogenicity as a commercially available aluminum-adjuvanted HBsAg vaccine, after two immunizations 28 days apart. MNAP application was associated with transient skin reactions (erythema, lump, scab), particularly evident when the antigen was delivered with the adjuvant. The thermostability of the adjuvanted antigen when incorporated in the HES-based matrix was also assessed by storing MNAP at 37, 45 or 50 °C for up to 6 months. We could demonstrate that antigenicity was retained at 37 and 45 °C and only a 10% loss was observed after 6 months at 50 °C. Our results are supportive of MNAP as an attractive alternative to classical syringe-based vaccination.

Fragmentation of poly(lactic acid) nanosheets and patchwork treatment for burn wounds.

Freestanding poly(L-lactic acid) (PLLA) nanosheets are mass-produced by a simple combination of a spin-coating-assisted multi-layering process and a peeling technique. The resulting PLLA nanosheets are fragmented by homogenization and then reconstructed into a "patchwork" sheet on various surfaces without any adhesive reagents. The patchwork is shown to offer excellent protection against burn wound infection with Pseudomonas aeruginosa, and may therefore be an alternative to conventional burn therapy for prevention of infection.