Simple coating with fibronectin fragment enhances stainless steel screw osseointegration in healthy and osteoporotic rats

Abstract

Metal implants are widely used to provide structural support and stability in current surgical treatments for bone fractures, spinal fusions, and joint arthroplasties as well as craniofacial and dental applications. Early implant-bone mechanical fixation is an important requirement for the successful performance of such implants. However, adequate osseointegration has been difficult to achieve especially in challenging disease states like osteoporosis due to reduced bone mass and strength. Here, we present a simple coating strategy based on passive adsorption of FN7-10, a recombinant fragment of human fibronectin encompassing the major cell adhesive, integrin-binding site, onto 316-grade stainless steel (SS). FN7-10 coating on SS surfaces promoted α5β1 integrin-dependent adhesion and osteogenic differentiation of human mesenchymal stem cells. FN7-10-coated SS screws increased bone-implant mechanical fixation compared to uncoated screws by 30% and 45% at 1 and 3 months, respectively, in healthy rats. Importantly, FN7-10 coating significantly enhanced bone-screw fixation by 57% and 32% at 1 and 3 months, respectively, and bone-implant ingrowth by 30% at 3 months compared to uncoated screws in osteoporotic rats. These coatings are easy to apply intra-operatively, even to implants with complex geometries and structures, facilitating the potential for rapid translation to clinical settings.

Experimental and computational examination of anastellin (FnIII1c)–polymer interactions

“…The RGD sequence allows binding to cell-bound integrin receptors, such as α5β1, to enable adhesion of cells to the extracellular matrix while the PHSRN sequence has a synergistic effect on this binding. 3 The RGD peptide sequence has been incorporated onto biomaterials, [4][5][6] in its linear form, or cyclic forms, or as part of a larger fragment in order to improve aspects of biocompatibility such as osseointegration. 4 Use of a protein fragment offers advantages over whole Fn such as improved stability and increased density of desired sequences on the surface.…”

“…3 The RGD peptide sequence has been incorporated onto biomaterials, [4][5][6] in its linear form, or cyclic forms, or as part of a larger fragment in order to improve aspects of biocompatibility such as osseointegration. 4 Use of a protein fragment offers advantages over whole Fn such as improved stability and increased density of desired sequences on the surface. 7 Another area of Fn that has been shown to elicit potentially useful interactions is the Cterminal fragment of the first FnIII domain (FnIII1c), known as anastellin, which has 76 amino acid residues.…”

Multifunctional biomaterial coatings: synthetic challenges and biological activity

“…These events can lead to the so-called foreign body reaction, which can eventually cause loosening of the implant, inflammation, coagulation or, in a secondary event, infections ( Figure 1A) (Anderson et al, 2008;Trindade et al, 2016). To circumvent these issues, biomaterials are coated with components of the extracellular matrix (ECM) such as proteins, specific peptide sequences or glycosaminoglycans (GAGs) (Geissler et al, 2000;LeBaron and Athanasiou, 2000;Lee et al, 2011b;Salbach et al, 2012;Chlupac et al, 2014;Agarwal et al, 2015). However, to address additional biological cues or to increase specificity and activity, multifunctional coatings are required ( Figure 1B).…”

Engineered protein coatings to improve the osseointegration of dental and orthopaedic implants

“…[30, 31] However, issues regarding batch-to-batch reproducibility constrain the potential of naturally derived materials. [31, 32] Furthermore, directly tethering cell-binding peptides to the implant surface limits the methods that can be employed to modify other coating properties. Alternatively, recombinant protein based coatings are attractive as they retain the bioactivity of naturally derived materials, can be manufactured reproducibly, and are highly customizable.…”

“…Alternatively, recombinant protein based coatings are attractive as they retain the bioactivity of naturally derived materials, can be manufactured reproducibly, and are highly customizable. [32, 33] …”