Sustained Release of IGF-1 by 3D Mesoporous Scaffolds Promoting Cardiac Stem Cell Migration and Proliferation

Abstract

Background/Aims: C-kit-positive cardiac stem cells (CSCs) may have potential as a treatment for cardiovascular disease. However, the low survival rates of c-kit-positive CSCs present a major challenge during the transplantation process. Methods: The hierarchical structure of the 3D cell scaffold was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and N₂ adsorption-desorption isotherms. Analyses of the proliferation and migration performances of the IGF-1 scaffold on c-kit-positive CSCs were conducted by experiments including QuantiT PicoGreen dsDNA and transwell assays. Results: In this study, we synthesized for the first time a novel hierarchical macro-mesoporous silica material (denoted MS15-c) in a one-pot procedure for the release of insulin-like growth factor-1 (IGF-1) and a three-dimensional (3D) cell scaffold. Both macropores and mesopores were visible in MS15-c and enabled the sustained release of IGF-1, extending its half-life and enhancing CSC proliferation and migration. Proliferation and migration were detected by QuantiT PicoGreen dsDNA and transwell assays, respectively. Moreover, an in vivo experiment was conducted to detect heart function with the addition of MS15-c. The new strategy proposed in this paper may extend the bio-applications of 3D cell scaffolds, thus permitting the sustained release of growth factors and efficient promotion of cell proliferation. Conclusion: This work successfully demonstrated an effective strategy for the construction of MS15-c cell scaffolds with hierarchical macro-mesoporous structures. The macro-mesoporous structures gave cell scaffolds the ability to release a growth factor to facilitate cell growth, while the scaffold structure promoted cell proliferation.

Effect of Bone Morphogenic Protein-2-Loaded Mesoporous Strontium Substitution Calcium Silicate/Recycled Fish Gelatin 3D Cell-Laden Scaffold for Bone Tissue Engineering

“…A steady release was important as a high concentration could cause various side effects, such as heterotopic bone formation, edema or inflammatory reactions [35]. In order to solve this problem, some studies have used the encapsulation of BMP-2 in micro-or nanoparticles and incorporated in the composite scaffolds [36]. Our previous results have shown that pre-loading of factors into raw materials had better sustained-release profiles as compared to direct loading of factors [19].…”

Incorporation of Calcium Sulfate Dihydrate into a Mesoporous Calcium Silicate/Poly-ε-Caprolactone Scaffold to Regulate the Release of Bone Morphogenetic Protein-2 and Accelerate Bone Regeneration

“…During the past few years, nano-porous bioscaffolds have been proven to be good methods for drug delivery and for controlled, sustained release of drug molecules. According to one report, a mesoporous scaffold was loaded with insulin-like growth factor 1 to induce cardiac stem cell proliferation and migration and it was shown to be a potential candidate for in vivo treatment [43]. To investigate whether a higher BMP-2 concentration ratio would increase bone regeneration, we used 3D printing to make nano-pore-sized scaffolds intended to provide a controlled release rate over a 6-month time period.…”

Engineering Functional Cardiac Tissues for Regenerative Medicine Applications

“…Engineered scaffolds, when paired with patient-specific stem cells, can be used to deliver novel therapies and advance regenerative medicine [46,50]. In the field of cardiac tissue engineering, polymeric biomaterials can be derived from natural or synthetic sources.…”

“…To accurately simulate their target environment, scaffolds require directed assembly of the biomaterial components using various approaches including casting, bioprinting, or electrospinning, which are covered in more detail later in this review. In the case of synthetic scaffolds, polymer functionalization using a variety of small molecules, peptides, and proteins is often required to facilitate cellular integration and maturation within the engineered tissue construct [48,50]. For any of these scaffolds to be a viable long-term translational option, they must support vascularization, either directly, or through their porous structure.…”