Injectable bioactive akermanite/alginate composite hydrogels for in situ skin tissue engineering.

In situ tissue engineering holds great promise in regenerative medicine owing to the utilization of the body's own regenerative capacity via recruiting host endogenous stem cells or tissue-specific progenitor cells to the site of injury. In this study, an injectable bioactive akermanite/alginate composite hydrogel was prepared for in situ tissue engineering using an akermanite bioceramic as a bioactive cross-linking component to provide bioactive ions such as Ca, Mg and Si. These bioactive ions on the one hand cross-link alginate to form injectable hydrogels in the presence of acidic amino acids and on the other hand function as bioactive stimuli to activate the wound healing process. The bioactive hydrogel exhibits specific activity in regulating cell behavior such as migration, proliferation and differentiation both in vitro and in vivo. Most interestingly, using a chronic wound healing model, we demonstrated for the first time that the composite hydrogel significantly enhances the healing of chronic wounds by recruiting stem cells, stimulating cell proliferation, and enhancing blood vessel formation and re-epithelialization. Our results indicate that the injectable bioactive composite hydrogels act as in situ tissue engineering scaffolds to stimulate the regeneration of skin tissue, and utilizing the interaction between the bioactive bioceramics and biopolymers, in which bioceramics function as both cross-linking agents and bioactive factors, is a versatile strategy for designing multifunctional bioactive biomaterials for wound healing and tissue engineering applications.

Self-Healing Elastin-Bioglass Hydrogels.

Tailorable hydrogels that are mechanically robust, injectable, and self-healable, are useful for many biomedical applications including tissue repair and drug delivery. Here we use biological and chemical engineering approaches to develop a novel in situ forming organic/inorganic composite hydrogel with dynamic aldimine cross-links using elastin-like polypeptides (ELP) and bioglass (BG). The resulting ELP/BG biocomposites exhibit tunable gelling behavior and mechanical characteristics in a composition and concentration dependent manner. We also demonstrate self-healing in the ELP/BG hydrogels by successfully reattaching severed pieces as well as through rheology. In addition, we show the strength of genetic engineering to easily customize ELP by fusing cell-stimulating "RGD" peptide motifs. We showed that the resulting composite materials are cytocompatible as they support the cellular growth and attachment. Our robust in situ forming ELP/BG composite hydrogels will be useful as injectable scaffolds for delivering cell and drug molecules to promote soft tissue regeneration in the future.

Design of a thermosensitive bioglass/agarose-alginate composite hydrogel for chronic wound healing.

Chronic wounds are a major health problem around the world, and there is a need to develop new types of dressing materials to enhance chronic wound healing. Humidity and angiogenic conditions are two important factors that may significantly affect the healing process. Therefore, a new wound dressing system based on bioglass (BG) and agarose-alginate (AA) has been designed, which can create a moist environment and improve the angiogenic condition of the wound area at the same time. The obtained BG/AA hydrogel has thermosensitivity allowing it to gel at physiological temperature through the interaction between the agarose and alginate polymer chains, and the chains can be further cross-linked by ions released from BG. The BG/AA hydrogel can promote migration of fibroblast and endothelial cells and it can also enhance the angiogenesis of endothelial cells in a fibroblast-endothelial cell co-culture model in vitro. The potential of the BG/AA hydrogel as a wound dressing has been further evaluated by using the rabbit ear ischemic wound model. The results demonstrate that the BG/AA hydrogel can enhance blood vessel and epithelium formation, which contribute to wound healing. The present study suggests that this new BG/AA hydrogel system may be used as a bioactive dressing for chronic wound healing.

Bioglass/alginate composite hydrogel beads as cell carriers for bone regeneration.

Cell carrier is a useful biomedical tool to deliver particular kind of cells to a specific site for cell therapy or tissue regeneration. In the current study, 45S5 bioglass (BG) was introduced into alginate (ALG) to generate BG/ALG composite hydrogel beads as cell carriers. The ions releasing behavior, dimensional stability and in vitro bioactivity of the beads were investigated. Results showed that the BG/ALG beads revealed similar calcium ion releasing behavior as compared with ALG beads. In addition, silicon ion releasing was detected in BG/ALG beads. BG/ALG and ALG beads shared similar dimensional stability, and BG/ALG beads could induce apatite deposition on their surface after being soaked in stimulated body fluid. Then, the effects of ion extracts from hydrogel beads on cell behavior were investigated. Results confirmed that extracts of BG/ALG beads could simulate proliferation and osteogenic differentiation of mesenchymal stem cells as well as angiogenesis of endothelial cells. Furthermore, MC3T3-E1 cells were successfully encapsulated in hydrogel beads. BG/ALG beads enhanced the cell proliferation and stimulated osteogenic differentiation of the encapsulated MC3T3-E1 cells as compared with ALG beads. Therefore, BG/ALG composite hydrogel beads loaded with bone forming cells may be useful tools for bone regeneration and tissue engineering applications.

The calcium silicate/alginate composite: preparation and evaluation of its behavior as bioactive injectable hydrogels.

In this study, an injectable calcium silicate (CS)/sodium alginate (SA) hybrid hydrogel was prepared using a novel material composition design. CS was incorporated into an alginate solution and internal in situ gelling was induced by the calcium ions directly released from CS with the addition of d-gluconic acid δ-lactone (GDL). The gelling time could be controlled, from about 30s to 10 min, by varying the amounts of CS and GDL added. The mechanical properties of the hydrogels with different amounts of CS and GDL were systematically analyzed. The compressive strength of 5% CS/SA hydrogels was higher than that of 10% CS/SA for the same amount of GDL. The swelling behaviors of 5% CS/SA hydrogels with different contents of GDL were therefore investigated. The swelling ratios of the hydrogels decreased with increasing GDL, and 5% CS/SA hydrogel with 1% GDL swelled by only less than 5%. Scanning electron microscopy (SEM) observation of the scaffolds showed an optimal interconnected porous structure, with the pore size ranging between 50 and 200 µm. Fourier transform infrared spectroscopy and SEM showed that the CS/SA composite hydrogel induced the formation of hydroxyapatite on the surface of the materials in simulated body fluid. In addition, rat bone mesenchymal stem cells (rtBMSCs) cultured in the presence of hydrogels and their ionic extracts were able to maintain the viability and proliferation. Furthermore, the CS/SA composite hydrogel and its ionic extracts stimulated rtBMSCs to produce alkaline phosphatase, and its ionic extracts could also promote angiogenesis of human umbilical vein endothelial cells. Overall, all these results indicate that the CS/SA composite hydrogel efficiently supported the adhesion, proliferation and differentiation of osteogenic and angiogenic cells. Together with its porous three-dimensional structure and injectable properties, CS/SA composite hydrogel possesses great potential for bone regeneration and tissue engineering applications.