Composite scaffolds: Bridging nanofiber and microsphere architectures to improve bioactivity of mechanically competent constructs

Abstract

Tissue engineering often benefits from the use of composites to produce an ideal scaffold. We present the focused development of a novel structure that combines the biomimetic properties of nanofibers with the robust mechanical aspects of the sintered microsphere scaffold to produce a composite scaffold that demonstrates an ability to mimic the mechanical environment of trabecular bone while also promoting the phenotype progression of osteoblast progenitor cells. These composite nanofiber/microsphere scaffolds exhibited a mechanical modulus and compressive strength similar to trabecular bone and exhibited degradation resulting in a mass loss of 30% after 24 weeks. The nanofiber portion of these scaffolds was sufficiently porous to allow cell migration throughout the fibrous portion of the scaffold and promoted phenotype progression through focal adhesion kinase-mediated activation of the transcription factor Runx2, control scaffolds not containing nanofibers did not demonstrate extensive cell migration or phenotype progression. Ultimately, the focal adhesion kinase activity on the composite nanofiber/microsphere scaffolds demonstrated causality over the production of the mature osteoblast marker, osteocalcin, and the development of a calcified matrix.

Biomimetic Structures: Biological Implications of Dipeptide‐Substituted Polyphosphazene–Polyester Blend Nanofiber Matrices for Load‐Bearing Bone Regeneration

“…For example, our laboratory recently demonstrated the incorporation of nanofi bers within the mechanically robust sintered microsphere matrix resulted in accelerated osteoblast phenotype development. [ 50 ] Inspired by the complex hierarchical structures that enable bone functions, we further designed and constructed a 3D biomimetic scaffold with an open central cavity to mimic the native bone structurally and mechanically. It is known that nanofi ber shrinkage results in signifi cant scaffold dimensional change due to the relaxation of stretched amorphous polymer chains.…”

The role of substrate topography on the cellular uptake of nanoparticles

“…As ECMs in vivo vary widely in chemical compositions 33 (collagen, fibronectin, glycosaminoglaycans), organization (topography, 53,54 porosity 55 ), and physical properties (stiffness 56 ), it is critically important to design nanoscale targets in concert with the physicochemical properties of the ECM to achieve optimized targeting efficiency. To date, for therapeutic purposes, the roles of substrate physicochemical properties such as stiffness of the substrate 57 and surface chemistry 58 have been investigated in regards to the cellular response.…”

Electrospinning of polymer nanofibers for tissue regeneration

“…Laurencin et al have since investigated a number of electrospun biodegradable nanofibrous scaffolds using polyphosphazenes, poly(lactide-co-glycolide) (PLGA), and poly (ε-caprolactone) (PCL) for wound healing [34], drug delivery [35], and regenerating soft [36][37][38][39][40][41][42] and hard tissues [43]. Furthermore, polyphosphazenenanohydroxyapatite composite [44] and polyphosphazene-PLGA blend [45] nanofiber scaffolds, as well as composite scaffolds comprised of poly(L-lactic acid) (PLLA) nanofibers and sintered microspheres [46], have been investigated for bone tissue engineering applications. Many Page 10 of 65 A c c e p t e d M a n u s c r i p t research groups have also investigated the electrospinning of a wide range of both natural and synthetic polymers for biomedical engineering applications [20,47].…”