Osteoinductive Biomaterial Geometries for Bone Regenerative Engineering

Abstract

Worldwide, more than 2.2 million patients undergo bone graft procedures annually. In each of these procedures an interface is formed between the host tissue and the graft material. Synthetic implants exhibit an interface with the host tissue and the formation of a homogenous interface consisting of bone and void of intervening soft tissue is desired (osseointegration); recent developments have highlighted the benefit of incorporating nanostructures at that interface. Autograft and allograft bone are frequently used for bone loss, nonunion fractures, and spinal fusions; however, both are plagued with complications either due to supply or inadequate graft properties. In contrast to bone tissue engineering, which uses a top-down approach to repair bone defects, bone regenerative engineering uses a bottom-up approach focused on strategies incorporating stem cells, biomaterials, and growth factors alone or in combination to generate or regenerate bone tissue. Early constructs developed for bone regenerative engineering utilized polymeric microstructures, presenting surface features with characteristic dimensions similar to that of a cell (1µm - 1000µm). These microstructures were typically biodegradable and demonstrated an excellent ability to match the mechanics of native bone tissue. They were also osteoconductive-capable of promoting osteoblast growth. On the other hand, the osteoinductive abilities of these microstructures were lacking. Osteoinduction, or the ability to promote the progression of a preosteoblastic cell to a mature osteoblast, historically was achieved in two ways: via the addition of nanoscale ceramics to the microstructures or via an external stimulus such as the addition of bone morphogenetic proteins (BMPs). More recent developments in bone regenerative engineering have utilized polymeric nanostructures (less than 1µm) with characteristic dimensions an order of magnitude or more less than that of a cell to stimulate and drive an osteoinductive response in the absence of growth factors. Despite strong literature evidence supporting the nanostructures' ability to be both osteoconductive and osteoinductive, there is still disparity regarding how nanostructures regulate the progression towards an osteoblastic phenotype. This review will explore unique micro- and nano-architectures, how they initiate osteoinductive signals through pathways similar to BMPs, and how these unique geometries can be translated to the clinic.

Profiling stem cell states in three-dimensional biomaterial niches using high content image informatics

“…These results correlated fast blue staining assay at 14 days, as well as with previous studies elucidating the development and applicability of these scaffolds for enhancing osteogenesis [12–14]. These results also corroborate with other recent studies elucidating that the intrinsic ability of hMSCs to differentiate into osteogenic lineage, even in the absence of osteogenic growth factors and supplements, can be enhanced by engineering the scaffold architecture (structure and topography) [36–38]. …”

Intrinsic Surface Effects of Tantalum and Titanium on Integrin α5β1/ ERK1/2 Pathway-Mediated Osteogenic Differentiation in Rat Bone Mesenchymal Stromal Cells

“…Given the use of a featureless structure with almost identical nano-scale roughness between the two substrate surfaces, we consider that the surface morphology was not obviously osteoinductive and had similar effects on cell behavior [17][18][19][20]. Indeed, the cells showed similar morphology and average spreading areas on the two substrates, which revealed similar influences of topographic guidance on cytoskeleton tension and membrane deformation, as the most important factors regulating cell commitment [31]. There was also no apparent difference in the water contact angles, indicating that the impact of surface Although the osteoinductive surrounding provided by OM has been regarded as one of the preconditions for cell osteogenic differentiation in vitro [32][33][34], using a normal culture environment may better reflect the actual effect of a material on osteogenesis; thus, in this study, both OM and CM were adopted for comprehensive testing.…”

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.…”