H-W Kim

Therapeutic bioactive microcarriers: co-delivery of growth factors and stem cells for bone tissue engineering.

Novel microcarriers made of sol-gel-derived bioactive glasses were developed for delivering therapeutic molecules effectively while cultivating stem cells for bone tissue engineering. Silica sols with varying concentration of Ca (0-30 mol.%) were formulated into microspheres ranging from 200 to 300 μm under optimized conditions. A highly mesoporous structure was created, with mesopore sizes of 2.5-6.3 nm and specific surface areas of 420-710 m(2)g(-1), which was highly dependent on the Ca concentration. Therapeutic molecules could be effectively loaded within the mesoporous microcarriers during microsphere formulation. Cytochrome C (cyt C), used as a model protein for the release study, was released in a highly sustainable manner, with an almost zero-order kinetics over a period of months; the amount released was ~2% at 9 days, and 15% at 40 days. A slight increase in the release rate was observed in the microcarrier containing Ca, which was related to the dissolution rate and pore size. The presence of Ca accelerated the formation of hydroxyapatite on the surface of the microcarriers. Cells cultured on the bioactive microcarriers were well adhered and distributed, and proliferated actively, confirming the three-dimensional substrate role of the microcarriers. An in vivo study performed in a rat subcutaneous model demonstrated the satisfactory biocompatibility of the prepared microspheres. As a therapeutic target molecule, basic fibroblast growth factor (bFGF) was incorporated into the microcarriers. A slow release pattern similar to that of cyt C was observed for bFGF. Cells adhered and proliferated to significantly higher levels on the bFGF-loaded microcarriers, demonstrating the effective role of bFGF in cell proliferative potential. It is believed that the developed mesoporous bioactive glass microspheres represent a new class of therapeutic cell delivery carrier, potentially useful in the sustainable delivery of therapeutic molecules such as growth factors, as well as in the support of stem cell proliferation and osteogenesis for bone tissue engineering.

Preparation of porous bioactive ceramic microspheres and in vitro osteoblastic culturing for tissue engineering application

Microparticulates are useful for directly filling defective tissues as well as for delivering cells and bioactive molecules in regenerative medicine. This paper reports on the production of bioactive ceramic microspheres with an interconnected macropore structure. The sol-gel derived calcium silicate powder was homogenized with an oligomeric Camphene melt, which was used as a novel porogen, and spherical-shaped microparticulates were obtained by an oil-in-water emulsion method. A porous structure was generated through the sublimation of Camphene within the calcium silicate-Camphene solidified blend under ambient conditions. The microspheres retained the crystalline phase of apatite and wollastonite during heat treatment and induced calcium phosphate precipitation under a body-simulating medium, showing the characteristics of bone-bioactive materials. Osteoblastic cells were observed to anchor to and spread well over the surface of the porous microspheres, and further to proliferate actively with culturing time. The bioactive and porous microspheres developed are considered potentially useful in the regeneration of hard tissues as a matrix for tissue engineering as well as a direct filling material.

Advanced Biomatrix Designs for Regenerative Therapy of Periodontal Tissues

Periodontitis is an inflammatory disease that causes loss of the tooth-supporting apparatus, including periodontal ligament, cementum, and alveolar bone. A broad range of treatment options is currently available to restore the structure and function of the periodontal tissues. A regenerative approach, among others, is now considered the most promising paradigm for this purpose, harnessing the unique properties of stem cells. How to make full use of the body’s innate regenerative capacity is thus a key issue. While stem cells and bioactive factors are essential components in the regenerative processes, matrices play pivotal roles in recapitulating stem cell functions and potentiating therapeutic actions of bioactive molecules. Moreover, the positions of appropriate bioactive matrices relative to the injury site may stimulate the innate regenerative stem cell populations, removing the need to deliver cells that have been manipulated outside of the body. In this topical review, we update views on advanced designs of biomatrices—including mimicking of the native extracellular matrix, providing mechanical stimulation, activating cell-driven matrices, and delivering bioactive factors in a controllable manner—which are ultimately useful for the regenerative therapy of periodontal tissues.

Biological Effects of Provisional Resin Materials on Human Dental Pulp Stem Cells

OBJECTIVES This study investigated the in vitro cytotoxicity as well as the proinflammatory cytokine expression of provisional resin materials on primary cultured human dental pulp stem cells (hDPSCs). METHODS Five commercially available provisional resin materials were chosen (SNAP [SN], Luxatemp [LT], Jet [JE], Revotek LC [RL], and Vipi block [VB]). Eluates that were either polymerizing or already set were added to hDPSCs under serially diluted conditions divided into three different setting times (25% set, 50% set, and 100% set) and incubated for 24 hours with 2× concentrated culture media. Cell cytotoxicity tests were performed by LDH assay and live and dead confocal microscope images. The expression of proinflammatory cytokines in SN and VB was measured using cytokine antibody arrays. Data were analyzed using repeated measures analysis of variance (ANOVA) or ANOVA followed by the Tukey post hoc test at a significance level of p<0.05. RESULTS Cytotoxicity greater than 30% was observed in the 50% diluted culture in SN, LT, and JE in the already set stage (p<0.05), while it was detected in SN and LT in early or intermediate stage samples. The cytotoxicity of SN, JE, and LT was greater with eluates from the polymerizing phase compared to that from already set samples (p<0.05), as observed by live and dead images. On the other hand, RL and VB did not exhibit cytotoxicity greater than 30%. Proinflammatory cytokines were not detected in 12.5% diluted culture with eluates from VB and early set stage SN. CONCLUSIONS The eluates from chemical-activated provisional resin materials during polymerization (SN, LT, and JE) were cytotoxic to hDPSCs and may adversely affect pulp tissue.