In vitro host response assessment of biomaterials for cardiovascular stent manufacture

Abstract

The deployment of a vascular stent during angioplasty has greatly reduced the risks of restenosis. However, the presence of the device still induces a host response as well as a mechanical action on the blood vessel wall and an alteration of the haemodynamics. Platelet and inflammatory cells can adhere on the stent surface and be activated to produce biochemical signals able to stimulate an excessive proliferation of the smooth muscle cells with the consequent obstruction of the vessel lumen. For these reasons, the host response to two of the materials used in stent manufacture, stainless steel and diamond-like carbon, was investigated in vitro. The data showed that stainless steel induced a higher level of host response both in terms of platelet aggregation and macrophage activation. However, the spreading of inflammatory cells was more accentuated on diamond-like carbon. The inflammatory cells produced levels of platelet-derived growth factor, a key signal in smooth muscle cell proliferation, similar to stainless steel thus suggesting that carbon coatings may not be able to prevent restenosis.

Substrate‐induced phenotypical change of monocytes/macrophages into myofibroblast‐like cells: A new insight into the mechanism of in‐stent restenosis

“…The treatment of the surfaces with PRP was performed to ensure the adsorption of plasma proteins onto the substrate surfaces, thus mimicking more closely the conditioning of the exposed surfaces occurring in vivo since the early phases of implantation. 3,11 The cells were incubated on EST, ECM, and Fib for 3 h at 378C, in 5% CO 2 , 95% air, then incubated overnight in growth medium enriched with 10% FCS for further 20 h. After 20 h, the medium supernatants were collected, centrifuged to eliminate unbound cells, and stored at 2708C until tested using ELISA kits for TGFb1 (DRG Diagnostic, Germany, catalogue number EIA-1864) and PDGF-BB (PeproTech EC, UK, catalogue no. 900-K04).…”

“…2 In particular, when stent struts penetrate the atherosclerotic plaque, they activate cells of the monocyte/ macrophage (MM) lineage as well as platelets. [2][3][4] At a later stage, a vascular smooth muscle cell (SMC) population embedded into the neointimal tissue often prevails. 3,5 Histological examination of the neointima extracellular matrix (ECM) has shown the anomalous prevalence of hyaluronan on collagen.…”

“…[2][3][4] At a later stage, a vascular smooth muscle cell (SMC) population embedded into the neointimal tissue often prevails. 3,5 Histological examination of the neointima extracellular matrix (ECM) has shown the anomalous prevalence of hyaluronan on collagen. 5,6 The accumulation of hyaluronan in ISR has been related to the typical composition of nonhealing tissues (e.g., chronic ulcer), where the synthesis of this mucopolysaccharide is not fully replaced by the deposition of mature ECM.…”

‘Bio-nano interactions: new tools, insights and impacts’: summary of the Royal Society discussion meeting

“…This 'binding' or biointeraction tendency of nanoscale surfaces results from their need to reduce their surface energy by binding available biomolecules [4], and can be used for a range of applications at the interface between medicine and engineering, including diagnostic devices, nanoenabled therapies such as targeted drug delivery, or for tissue engineering, as summarized in figure 3 [5]. Indeed, biointeractions have long been understood to determine the fate of implant materials such as stent coatings, where integration of the device into the body requires the adsorption of a specific set of proteins, while binding of the wrong proteins leads to immune recognition and subsequent rejection of the implant [6][7][8]. Similarly, bio-nano interactions and protein adsorption at nanoscale surfaces play key roles in cellular adhesion, mobility and phenotype development on material surfaces [9,10].…”

Stainless Steel Ions Stimulate Increased Thrombospondin-1-Dependent TGF-Beta Activation by Vascular Smooth Muscle Cells: Implications for In-Stent Restenosis

“…Yet, the mechanisms underlying this response are not understood. High concentrations of metal ions are toxic to VSMCs in vitro and sublethal concentrations stimulate both inflammatory and fibrotic reactions [11,12]. Stainless steel (SS) is particularly conducive to stimulation of fibrous tissue formation and inflammatory (allergic) responses, which are associated with increased rates of restenosis [11].…”