Patients with diabetes experience delayed wound healing because of the uncontrolled glucose level in their bloodstream, which leads to impaired function of white blood cells, poor circulation, decreased production and repair of new blood vessels. Treatment using polydeoxyribonucleotide (PDRN), which is a DNA extracted from the sperm cells of salmon, has been introduced to accelerate the healing process of diabetic wounds. To accelerate the wound-healing process, sustained delivery of PDRN is critical. In this study, taking advantage of the non-invasive gelation property of alginate, PDRN was loaded inside the hydrogel (Alg-PDRN). The release behavior of PDRN was altered by controlling the crosslinking density of the Alg hydrogel. The amount of PDRN was the greatest inside the hydrogel with the highest crosslinking density because of the decreased diffusion. However, there was an optimal degree of crosslinking for the effective release of PDRN. In vitro studies using human dermal fibroblasts and diabetes mellitus fibroblasts and an in ovo chorioallantoic membrane assay confirmed that the Alg-PDRN hydrogel effectively induced cell proliferation and expression of angiogenic growth factors and promoted new blood vessel formation. Its effectiveness for accelerated diabetic wound healing was also confirmed in an in-vivo animal experiment using a diabetic mouse model.
In this study, we
report the development of a hyaluronic acid (HA)-based
composite hydrogel containing calcium fluoride (CaF2) with
good biocompatibility and antibacterial properties for multifunctional
wound dressing applications. CaF2 was newly selected for
incorporation within HA because it can release both Ca2+ and F– ions, which are well-known ions for affecting
cell proliferation and inhibiting bacterial growth, respectively.
In particular, an in situ precipitation process enables easy control
over the released amount of F– ions by simply adjusting
the precursor solutions (calcium chloride (CaCl2) and ammonium
fluoride (NH4F)) used for the CaF2 precipitation.
CaF2 particles were uniformly embedded within a HA-based
pure hydrogel using an in situ precipitation process. Through variation
of the CaCl2 and NH4F concentrations used in
the precipitation as well as the precipitation time, composite hydrogels
with different ion-release profiles were obtained. By controlling
the precipitation time, especially for 10 min and after 30 min, large
differences in the ion-release profiles as a function of CaF2 concentration were observed. A shorter precipitation time resulted
in faster release of fluoride, whereas for the 30 min and 1 h samples,
sustained ion release was achieved. Colony tests and live/dead assays
using Escherichia coli and Staphylococcus
aureus revealed a lower density of bacteria on the CaF2 composite hydrogels than on the pure hydrogel for both strains.
In addition, improved cellular responses such as cell attachment and
proliferation were also observed for the CaF2 composite
hydrogels compared to those for the pure hydrogel. Furthermore, the
composite hydrogels exhibited excellent wound healing efficiency,
as evidenced by an in vitro cell migration assay. Finally, monitoring
of the wound closure changes using a full-thickness wound in a rat
model revealed the accelerated wound healing capability of the CaF2 composite hydrogels compared with that of the pure hydrogel.
Based on our findings, these CaF2 composite hydrogels show
great potential for application as advanced hydrogel wound dressings
with antibacterial properties and accelerated wound-healing capabilities.
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.
High EMT scores of ECS tumors in LNM predict an unfavorable prognosis and systemic dissemination more accurately than the simple presence of ECS in LNM in head and neck cancer patients.
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