Abstract
The performance of biomaterials designed for bone repair depends, in part, on the ability of the material to support the adhesion and survival of mesenchymal stem cells (MSCs). In this study, a nanofibrous bone-mimicking scaffold was electrospun from a mixture of polycaprolactone (PCL), collagen I, and hydroxyapatite (HA) nanoparticles with a dry weight ratio of 50/30/20 respectively (PCL/col/HA). The cytocompatibility of this tri-component scaffold was compared with three other scaffold formulations: 100% PCL (PCL), 100% collagen I (col), and a bi-component scaffold containing 80% PCL/20% HA (PCL/HA). Scanning electron microscopy, fluorescent live cell imaging, and MTS assays showed that MSCs adhered to the PCL, PCL/HA and PCL/col/HA scaffolds, however more rapid cell spreading and significantly greater cell proliferation was observed for MSCs on the tri-component bone-mimetic scaffolds. In contrast, the col scaffolds did not support cell spreading or survival, possibly due to the low tensile modulus of this material. PCL/col/HA scaffolds adsorbed a substantially greater quantity of the adhesive proteins, fibronectin and vitronectin, than PCL or PCL/HA following in vitro exposure to serum, or placement into rat tibiae, which may have contributed to the favorable cell responses to the tri-component substrates. In addition, cells seeded onto PCL/col/HA scaffolds showed markedly increased levels of phosphorylated FAK, a marker of integrin activation and a signaling molecule known to be important for directing cell survival and osteoblastic differentiation. Collectively these results suggest that electrospun bone-mimetic matrices serve as promising degradable substrates for bone regenerative applications.
Highlights
Bone is the second most transplanted tissue in the body
In the current investigation we evaluated mesenchymal stem cell (MSC) responses to the bone-like tri-component PCL/col/HA scaffolds (50%PCL/ 30%col I/20% HA), in direct comparison with three other scaffold formulations; 100% PCL, 100% collagen I, and a PCL/20% HA (PCL/HA) composite (80%PCL/20%HA)
In comparison, blending collagen I with PCL significantly increased scaffold strength relative to scaffolds composed of collagen I alone, providing a useful alternative to chemical cross-linking of collagen fibers
Summary
Bone is the second most transplanted tissue in the body (after blood transfusions). Autografting of bone is extensively employed in orthopedic and dental surgeries; the harvesting of the patient’s own bone requires a second surgery that can greatly increase the time and cost for the procedure. Nonunion at the repair site is a common problem, and iliac crest harvest can lead to complications in as many as 20% of patients [1,2,3] Another limitation is that the supply of bone material from the iliac crest may be inadequate when a large amount of graft material is required [4]. For these reasons, there is an immediate need for a biomaterial that can either substitute for autografted bone or serve as a temporary matrix that induces regeneration of native bone at implant sites. PCL is a semicrystalline, aliphatic polyester that has a much lower rate of degradation than collagen, and is useful in a composite scaffold for increasing mechanical strength, and fine-tuning the rate of resorbability [19,20,21]
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