Injectable cell-laden hybrid bioactive scaffold containing bioactive glass microspheres.

The rising incidence of bone disorders has resulted in the need for minimally invasive therapies to meet this demand. Injectable bioactive filler, alone or with cells, could be applied in a minimally invasive manner to fulfill irregular cavities in non-load bearing sites, which do not require high mechanical properties. Thermosensitive chitosan hydrogels that transition from a liquid to a mechanically stable solid at body temperature provide interesting features as in-situ injectable cytocompatible biomaterials, but they are not osteoconductive. Osteoconductivity can be applied in combination with bioactive ceramics e.g., 45S5-Bioglass® (BG). However, BG addition in chitosan hydrogels results in pH elevation, due to rapid ions release, which adversely affects gel formation, mechanical properties, and cytocompatibility. To address this, we created hybrid hydrogels, where BG is concentrated in chitosan-based microbeads, incorporated in in-situ gelling chitosan hydrogels. We then compared the hybrid hydrogels' properties to chitosan hydrogels with homogenously distributed BG. By varying the stirred emulsification process, BG percentage, and CH formulation, we could tune the microbeads' properties. Incorporation of BG microbeads drastically improved the hydrogel's compressive modulus in comparison to homogeneously distributed BG. It also strongly increased the survival and metabolic activities of encapsulated cells. Calcium/phosphate increase on BG microbeads suggests hydroxyapatite formation. The small diameter of microbeads allows minimally invasive injection through small needles. The feasibility of freezing and thawing microbeads provides the possibility of long-term storage for potential clinical applications. These data indicate that this hybrid hydrogel forms a promising injectable cell-laden bioactive biomaterial for the treatment of unloaded bone defects.

Aging of Bioactive Glass-Based Foams: Effects on Structure, Properties, and Bioactivity.

Bioactive glasses (BG) possess significant bone-bonding and osteogenic properties that support their use for bone defects repair in orthopaedic and dental procedures. Recent advancement enables the manufacturing of BG-based scaffolds providing structural support during bone regeneration. Despite the wide number of studies on BG and BG-based materials, little information on their aging mechanisms and shelf life is available in the literature. In this study, the evolution of chemical species on BG-based foams was investigated via accelerated tests in the presence of CO2 and humidity. The aging process led to the formation of carbonates (Na2CO3 and CaCO3) and hydrocarbonates (NaHCO3). The amount and composition of nucleated species evolved with time, affecting the structure, properties, and bioactivity of the scaffolds. This study provides a first structured report of aging effects on the structure and chemico-physical properties of bioactive glass-based scaffolds, offering an insight about the importance of their storage and packaging.

Chondroitin sulfate and epidermal growth factor immobilization after plasma polymerization: a versatile anti-apoptotic coating to promote healing around stent grafts.

Bioactive coatings constitute an interesting approach to enhance healing around implants, such as stent-grafts used in endovascular aneurysm repair. Three different plasma techniques, namely NH3 plasma functionalization and atmospheric- or low-pressure plasma polymerization, are compared to create amino groups and covalently bind CS and EGF bioactive molecules on PET. The latter presents the greatest potential. CS + EGF coating is shown to strongly decrease cell apoptosis and cell depletion in serum-free medium, while increasing cell growth compared to unmodified PET. This versatile biomimetic coating holds promise in promoting vascular repair around stent-grafts, where resistance to apoptosis is a key issue.

Stimulation of cell growth and resistance to apoptosis in vascular smooth muscle cells on a chondroitin sulfate/epidermal growth factor coating.

Deficient healing after endovascular aneurysm repair is thought to be related to the pro-apoptotic environment in abdominal aortic aneurysms and inertness of the graft materials. A bioactive coating containing both chondroitin sulfate (CS) and epidermal growth factor (EGF) was developed in order to increase the growth and resistance to apoptosis of vascular smooth muscle cells (VSMC) on biomaterials surfaces. CS and EGF were covalently grafted using carbodiimide chemistry and the coating was characterized and optimized using ellipsometry, static contact angle and ToF-SIMS. Its potential to improve cell adhesion, growth and resistance to apoptosis was assessed in vitro with rat aortic VSMC. Results showed that CS and EGF immobilization allowed for the creation of a uniform coating that increased cell adhesion, growth and resistance to apoptosis in serum-free medium. Overall, CS and EGF possess great potential as bioactive anti-apoptotic mediators for vascular repair.

Chondroitin-4-sulfate: a bioactive macromolecule to foster vascular healing around stent-grafts after endovascular aneurysm repair.

Deficient healing after endovascular aneurysm repair with a stent-graft is thought to be related to pro-apoptotic environment in abdominal aortic aneurysms and inertness of graft materials. We developed a bioactive coating containing chondroitin-4-sulfate and assessed its potential to improve cell adhesion, viability and resistance to apoptosis on PET surfaces. Coatings of collagen type I and CS were prepared and characterized by DMMB, FT-IR, DSC, SEM and contact angle goniometry. Preliminary cell culture experiments with vascular smooth muscle cells showed increased adhesion and viability in serum-free medium on CS-coated surfaces compared to control PET films.