Nanofiber-microsphere (nano-micro) matrices for bone regenerative engineering: a convergence approach toward matrix design

Abstract

Bone is an essential organ for health and quality of life. Due to current shortfalls in therapy for bone tissue engineering, scientists have sought the application of synthetic materials as bone graft substitutes. As a composite organic/inorganic material with significant extra cellular matrix (ECM), one way to improve bone graft substitutes may be to engineer a synthetic matrix that is influenced by the physical appearance of natural ECM networks. In this work, the authors evaluate composite, hybrid scaffolds for bone tissue engineering based on composite ceramic/polymer microsphere scaffolds with synthetic ECM-mimetic networks in their pore spaces. Using thermally induced phase separation, nanoscale fibers were deposited in the pore spaces of structurally sound microsphere-based scaffold with a density proportionate to the initial polymer concentration. Porosimetry and mechanical testing indicated no significant changes in overall pore characteristics or mechanical integrity as a result of the fiber deposition process. These scaffolds displayed adequate mechanical integrity on the scale of human trabecular bone and supported the adhesion and proliferation of cultured mouse calvarial osteoblasts. Drawing from natural cues, these scaffolds may represent a new avenue forward for advanced bone tissue engineering scaffolds.

Nanostructured surface bioactive composite scaffold for filling of bone defects

“…These data indicate that the scaffold has good biocompatibility: human MSCs adhered to and proliferated on the surface of the scaffold, and their metabolic activity was normal. The similarity of the XRD TEM, and BET results of natural bone and collagen fibers mineralized with nanosized HA, [6][7][8][9][10][11][12][13][14][15][16][17][18] may explain the biomimetic effect in terms of osteointegration, cell seeding, and formation of new bone. However the hydrophobic PCL could hamper differentiation of MSCs.…”

“…Therefore, tissue-engineering scaffolds can be engineered by fabricating protein-polysaccharide composite nanofibers. Scaffolds with both micro-and nano-scale structures promote cell growth and new tissue formation [3,11]. Scaffolds should have a large surface area and high porosity to facilitate cell attachment and nutrient diffusion [12].…”

Nanofiber/Microsphere Hybrid Matrices In Vivo for Bone Regenerative Engineering: A Preliminary Report

“…The resulting values of both total cell number and GFP positive cell number were plotted as a function of distance from the periphery of the matrix (figure 2C–2E) are consistent with both the previous in vitro data on matrix DNA content, the total population of nuclei was higher in control matrices compared to hybrid matrices (figure 2D, p < 0.01). 3 Although the total number of cells was lower, the fraction of these total cells that had positive collagen promoter activity as determined through GFP expression was significantly higher on hybrid matrices compared to control matrices (figure 2F, p = 0.02). Taken together, these data indicate that fewer cells are inhabiting the nanofiber-permeated matrices, but a higher fraction of those cells are producing type I collagen and are thus more likely to be in the process of committing to the osteogenic lineage and therefore may be more beneficial for regenerative engineering.…”

“…4–6 Recently our group has created matrices with nanofibers placed in the pore spaces of these sintered microsphere matrices. 3 Since natural human bone has large quantities of extracellular matrix (ECM), incorporation of such matrix elements in an advanced biomaterial matrix is well reasoned.…”

“…These hybrid matrices were shown to support the adherence and proliferation of the immortalized mouse pre-osteoblast cell line MC3T3-E1. 3 Furthermore, these constructs were shown to influence the expression of Runx2 and osteocalcin, two important markers of osteoblast differentiation and function. 8 To have a successful clinical application, however, the efficacy of these matrices needs to be tested both in vitro and in vivo to determine their ability to function as bone graft substitutes.…”