Effect of rat bone marrow derived–stem cell delivery from serum-loaded oxidized alginate–gelatin–biphasic calcium phosphate hydrogel for bone tissue regeneration using a nude mouse critical-sized calvarial defect model

Abstract

Blood serum contains various kinds of proteins which are necessary for tissue repair and regeneration process. Defect healing of fractured bone is initiated by the influx of blood and then clot formation. Thus, proteins in serum may have the ability to stimulate the bone regeneration process. In this work, we investigated the fabrication of serum-loaded oxidized alginate–gelatin–biphasic calcium phosphate hydrogels with various contents of blood serum (0%, 5%, 10%, and 15% in % v/v) to evaluate the stimulatory effect of serum proteins on bone regeneration. This system was also evaluated for rat bone marrow–derived stem cell delivery to get faster bone healing. The serum-loaded oxidized alginate–gelatin–biphasic calcium phosphate hydrogel samples were characterized by scanning electron microscopy, porosity meter, X-ray diffraction, and Fourier transform infrared for morphology and phase characterization together with their mechanical behavior. Protein release behavior, degradation, and swelling of the samples were studied. In vitro study was performed using bone marrow–derived stem cells to study cell attachment, viability, and proliferation. These studies revealed the best cell attachment and highest proliferation for 5% serum-loaded oxidized alginate–gelatin–biphasic calcium phosphate hydrogel scaffold. This composition also showed the ability to deliver stem cell in the defect zone which significantly improved the bone regeneration extent found in the in vivo animal model. In vivo study revealed that for the critical 5-mm calvarial defect into nude mouse skull, the 5% serum-loaded sample with bone marrow–derived stem cells shows the best bone regeneration potential.

Oxidized Alginate-Based Hydrogels for Tissue Engineering Applications: A Review

“…After oxidizing alginate by sodium periodate in the dark to the desired period of time, the reaction can be stopped by adding ethylene glycol into the reaction mixture. The OA product can be purified by dialysis of the obtained solution against deionized water, − distilled water, − or can be precipitated by adding sodium chloride and ethanol into the solution. ,, For obtaining dried OA, the dialyzed solution can be dried by lyophilization, whereas the precipitated product can be vacuum-dried at room temperature or oven-dried at 40–50 °C …”

“…The incorporation of blood serum into OA/gelatin/biphasic calcium phosphate composite hydrogels for bone TE was studied by Paul et al Scaffolds were produced by freeze-drying the hydrogels containing various concentrations of blood serum. Increasing blood serum content in the samples resulted in a higher degradation rate of samples.…”

Alginate-Based Composites for Corneal Regeneration: The Optimization of a Biomaterial to Overcome Its Limits

“…The investigations about biomedical applications of oxidized alginate (OA) are continuously incrementing and generating curiosity [ 42 ]. For example, the partial oxidation of alginate allowed the provision of the controlled degradation kinetics of hydrogels and also to manage the release of incorporated factors, as is also demonstrated in other tissue regeneration fields [ 182 , 183 ].…”

Augmenting in vitro osteogenesis of a glycine–arginine–glycine–aspartic-conjugated oxidized alginate–gelatin–biphasic calcium phosphate hydrogel composite and in vivo bone biogenesis through stem cell delivery

“…23 We also mechanized the hydrogel-BCP system and modified it with various percentages of blood serum for housing and delivering rat bone marrow stem cells. 24 Although the blood serum contains numerous proteins, growth factors and ECMs, it is not likely to be useful clinically for patients with chronic or acute illnesses with concerns over microbial infection and transmission of blood-borne illnesses.…”