Seol-Ha Jeong

Polyurethane-silica hybrid foams from a one-step foaming reaction, coupled with a sol-gel process, for enhanced wound healing

Polyurethane (PU)-based dressing foams have been widely used due to their excellent water absorption capability, optimal mechanical properties, and unequaled economic advantage. However, the low bioactivity and poor healing capability of PU limit the applications of PU dressings in complex wound healing cases. To resolve this problem, this study was carried out the hybridization of bioactive silica nanoparticles with PU through a one-step foaming reaction that is coupled with the sol-gel process. The hybridization with silica did not affect the intrinsically porous microstructure of PU foams with silica contents of up to 10wt% and where 5-60nm silica nanoparticles were well dispersed in the PU matrix, despite slight agglomerations. The incorporated silica enhanced the mechanical performance of PU by proffering better flexibility and durability as well as maintaining good water absorption capabilities and the WVTR characteristics of pure PU foam. The silica of PU-10wt% Si foams was gradually dissolved and released under physiological conditions during a 14-day immersion period. The in vitro cell attachment and proliferation tests showed significant improvements in terms of the biocompatibility of PU-Si hybrid foams and demonstrated the effects of silica on cell growth. More significantly, the superior healing capability of PU-Si as a wound dressing in comparison to PU-treated wounds was verified through in vivo animal tests. Full-thickness wounds treated with PU-Si foams exhibited faster wound closure rates as well as accelerated collagen and elastin fiber regeneration in newly formed dermis, which was ultimately completely covered by a new epithelial layer. It is clear that PU-Si hybrid foams have considerable potential as a wound dressing material geared for accelerated, superior wound healing.

Long-lasting and bioactive hyaluronic acid-hydroxyapatite composite hydrogels for injectable dermal fillers: Physical properties and in vivo durability

Hyaluronic acid (HAc)–hydroxyapatite (HAp) composite hydrogels were developed to improve the biostability and bioactivity of HAc for dermal filler applications. Two kinds of HAc-HAp composite fillers were generated: HAcmicroHAp and HAc-nanoHAp composites. HAc-microHAp was fabricated by mixing HAp microspheres with HAc hydrogels, and HAc-nanoHAp was made by in situ precipitation of nano-sized HAp particles in HAc hydrogels. Emphasis was placed on the effect of HAp on the durability and bioactivity of the fillers. Compared with the pure HAc filler, all of the HAc-HAp composite fillers exhibited significant improvements in volumetric maintenance based on in vivo tests owing to their reduced water content and higher degree of biointegration between the filler and surrounding tissues. HAc-HAp composite fillers also showed noticeable enhancement in dermis recovery, promoting collagen and elastic fiber formation. Based on their long-lasting durability and bioactivity, HAc-HAp composite fillers have great potential for soft tissue augmentation with multifunctionality.

Enhancement of bio-stability and mechanical properties of hyaluronic acid hydrogels by tannic acid treatment

Hyaluronic acid (HA) has been widely investigated because of its excellent biocompatibility and its ability to form hydrogels with various chemical modifications. However, HA hydrogels undergo rapid degradation and exhibit poor mechanical stability under physiological conditions. Tannic acid (TA), a naturally occurring polyphenol found in plants and fruits, has recently attracted interest as a crosslinking agent because of its abundant hydroxyl groups. In this study, we prepared HA hydrogels chemically crosslinked by polyethylene glycol diglycidyl ether (PEGDE) and treated with TA in an attempt to enhance the physical properties of HA hydrogels. TA acts as a physical crosslinker owing to the strong hydrogen bonding between TA and PEGDE, resulting in improved mechanical properties that support both cell attachment and proliferation without any sign of cytotoxicity. The enzymatic stability of the HA-TA hydrogels was significantly enhanced with the addition of TA, which was attributed to the hyaluronidase inhibition activity of TA. Additionally, the antioxidant potential of TA resulted in good resistance to degradation by reactive oxygen species, which can be generated in human tissues.

Biomimetic Coating of Hydroxyapatite on Glycerol Phosphate-Conjugated Polyurethane via Mineralization

In this study, glycerol phosphate was introduced into polyurethane (PU) to promote the coating stability of hydroxyapatite (HA) during its mineralization on the PU surface. Glycerol phosphate was successfully conjugated with the PU chain during polymerization. Phosphate groups in glycerol phosphate accelerated the nucleation of HA under calcium phosphate ion-rich conditions (concentrated simulated body fluid), resulting in the enhancement of structural stability. The robust interface between HA and PU also improved mechanical properties. Hydrophilic phosphate groups and bioactive HA improved in vitro cellular responses in terms of the attachment and proliferation of L929 fibroblasts and MC3T3-E1 preosteoblasts. Thus, the highly elastic and bioactive PU-gp-HA could be a promising candidate for tissue engineering applications that experience frequent deformation, including diverse cartilage replacements.

Acceleration of the healing process of full-thickness wounds using hydrophilic chitosan–silica hybrid sponge in a porcine model:

In this study, we evaluated the surface characterization of a novel chitosan–silica hybridized membrane and highlighted the substantial role of silica in the wound environment. The chemical coupling of chitosan and silica resulted in a more condensed network compared with pure chitosan, which was eventually able to stably maintain its framework, particularly in the wet state. In addition, we closely observed the wound-healing process along with the surface interaction between chitosan–silica and the wound site using large-surface-area wounds in a porcine model. Our evidence indicates that chitosan–silica exerts a synergetic effect of both materials to promote a remarkable wound-healing process. In particular, the silica in chitosan–silica accelerated wound closure including wound contraction, and re-epithelialization via enhancement of cell recruitment, epidermal maturity, neovascularization, and granulation tissue formation compared with pure chitosan and other commercial dressing materials. This advanced wound dressing material may lead to effective treatment for problematic cutaneous wounds and can be further applied for human skin regeneration.

Hyaluronic acid-Hydroxyapatite Nanocomposite Hydrogels for Enhanced Biophysical and Biological Performance in a Dermal Matrix

A hyaluronic acid (HAc)-hydroxyapatite (HAp) nanocomposite (HAc-nanoHAp) hydrogel was fabricated through an in situ precipitation process for mechanical and biological enhancement as a soft tissue augmentation product. In this study, these composite hydrogel fillers were analyzed from three different perspectives and compared with pure HAc hydrogel for soft tissue augmentation application: (1) rheological behaviors, (2) in vivo lateral diffusion under mouse skin, and (3) wrinkle improvement in a photo-aged mouse model. HAc-nanoHAp provided great improvement to wrinkles because of its higher stiffness and gel cohesiveness in comparison with that of pure HAc. HAc-nanoHAp also presented great enhancement in strengthening the dermal matrix by stimulating the synthesis of collagen and elastin. Thus, HAc-nanoHAp filler has great potential as a soft tissue augmentation product, improving the biophysical and biological performance in skin tissue.

Calcium Phosphate–Collagen Scaffold with Aligned Pore Channels for Enhanced Osteochondral Regeneration

This study reports the development of a bilayered scaffold with aligned channels produced via a sequential coextrusion and unidirectional freezing process to facilitate upward bone-marrow stem-cell migration. The biomimetic scaffold with collagen and biphasic calcium phosphate (BCP) layers is successfully fabricated with matching of the cartilage and bone layers. The aligned structure results in an enhancement of the compressive strength, and the channels enable tight anchoring of the collagen layers on the BCP scaffolds compared with a randomly structured porous scaffold. An in vitro evaluation demonstrates that the aligned channels guide the cells to attach on the surface in highly stretched shapes and migrate upward faster than the random structure. In addition, in vivo assessment reveals that the aligned channels yield superior osteochondral tissue regeneration compared with the random structure. Moreover, the channel diameter greatly affects the tissue regeneration, and the scaffold with a channel diameter of ≈270 µm exhibits the optimal regeneration because of sufficient nutrient supply and adequate tissue ingrowth. These findings indicate that the introduction of aligned channels to a bilayered scaffold provides an effective approach for osteochondral tissue regeneration.

Chitosan-Based Dressing Materials for Problematic Wound Management

Wound healing is a complex mechanism involving a variety of factors and is a representative process of tissue growth and regeneration in our body. Surface-based interactions between the dressing material and the wound may significantly influence the healing phase. Advances in understanding the mechanism of wound healing have led to the development of numerous dressing materials that can accelerate the healing process. However, these materials have a passive role in wound healing. It is therefore necessary to develop novel wound dressing materials, especially effective for clinically problematic wounds. Chitosan-based dressing materials are considered suitable for clinically problematic wounds as they exhibit several characteristic features, such as facilitating hemostasis, enhanced wound healing during the inflammatory and proliferative phases, antimicrobial effect, etc. Here, we review the current status of clinically available dressing materials and studies on the biological characteristics of chitosan, and discuss the potential applications of chitosan in multi-functional dressing materials for accelarated wound healing.

In vitro and in vivo evaluation of polylactic acid-based composite with tricalcium phosphate microsphere for enhanced biodegradability and osseointegration:

A biodegradable polylactic acid composite containing tricalcium phosphate microsphere was fabricated. The composite exhibited enhanced biocompatibility and a well-interconnected porous structure that enabled tissue ingrowth after degradation. The tricalcium phosphate microspheres had an average size of 106 ± 43 μm and were incorporated into the polylactic acid matrix using a high-shear mixer. The resulting bioactivity and hydrophilicity were enhanced to levels comparable to those of a polylactic acid composite containing tricalcium phosphate powder, which is a well-known material used in the medical field. An accelerated 30-day degradation test in HCl revealed successful generation of an open porous structure with ∼98% interconnectivity in the polylactic acid–tricalcium phosphate microsphere composite, demonstrating the potential of this material to induce enhanced osseointegration in the later stage of bone regeneration. The early stage osseointegration was also evaluated by implanting the composite in vivo using a rabbit femoral defect model. After 16 weeks of implantation, the bone-to-implant contact ratio of the polylactic acid–tricalcium phosphate microsphere composite was enhanced owing to tissue ingrowth through the generated pores near the surface.

Facile strategy involving low-temperature chemical cross-linking to enhance the physical and biological properties of hyaluronic acid hydrogel

Here, we present a novel strategy to fabricate hyaluronic acid (HA) hydrogels with excellent physical and biological properties. The cross-linking of HA hydrogel by butanediol diglycidyle ether (BDDE) was characterized under different reaction temperatures, and the resulting physical properties (i.e., the storage modulus and swelling ratio) were measured. The ratio between the cross-linking rate (a strengthening effect) and the hydrolysis rate (a weakening effect) was much greater with lower cross-linking temperatures after sufficient cross-linking time, resulting in a noticeably higher storage modulus. As the cross-linking temperature decreased, the formed HA hydrogel structure became denser with smaller pores. Moreover, the introduction of low-temperature HA cross-linking strategy also resulted in an enhanced several important characteristics of HA hydrogels including its enzymatic resistivity and its ability to elicit a cellular response. These results indicate the performance of HA hydrogels can be markedly enhanced without further additives or modifications, which is expected to contribute to the advancement of applications of HA hydrogels in all industrial fields.