In vivo modulation of foreign body response on polyurethane by surface entrapment technique

Abstract

Implanted polymeric materials, such as medical devices, provoke the body to initiate an inflammatory reaction, known as the foreign body response (FBR), which causes several complications. In this study, polyurethane (Tecoflex®, PU) surface modified with the nonionic surfactant Tween80® (PU/T80) and the cell adhesive PLL-RGD peptide (PU/PLL-RGD) by a previously described entrapment technique were implanted in the peritoneal cavity of Wistar rats for 30 days. Implants were retrieved and examined for tissue reactivity and cellular adherence by various microscopic and analytical techniques. Surface-induced inflammatory response was assessed by real-time PCR based quantification of proinflammatory cytokine transcripts, namely, TNF-α and IL-1β, normalized to housekeeping gene GAPDH. Cellular adherence and their distribution profile were assessed by microscopic examination of H&E stained implant sections. It was observed that PU/PLL-RGD followed by the bare PU surface exhibited severe inflammatory and fibrotic response with an average mean thickness of 19 and 12 μm, respectively, in 30 days. In contrast, PU/T80 surface showed only a cellular monolayer of 2-3 μm in thickness, with a mild inflammatory response and no fibrotic encapsulation. The PU/PLL-RGD peptide-modified substrate promoted an enhanced rate of macrophage cell fusion to form foreign body giant cell (FBGCs), whereas FBGCs were rarely observed on Tween80®-modified substrate. The expression levels of proinflammatory cytokines (TNF-α and IL-1β) were upregulated on PU/PLL-RGD surface followed by bare PU, whereas the cytokine expressions were significantly suppressed on PU/T80 surface. Thus, our study highlights modulation of foreign body response on polyurethane surfaces through surface entrapment technique in the form of differential responses observed on PLL-RGD and Tween80® modified surfaces with the former effective in triggering tissue cell adhesion thereby fibrous encapsulation, while the later being mostly resistant to this phenomenon.

Shifts in macrophage phenotype at the biomaterial interface via IL-4 eluting coatings are associated with improved implant integration

“…Similarly, promoting transient shifts in macrophage polarization in the early host response represents an improved approach as compared to strategies which seek to evade the host immune response. Previous studies using surface modification of biomaterials and coatings to escape the innate immune system have shown only modest improvements at early stages of the host response against biomaterials and few improvements in long-term performance [56-60]. Finally, the present delivery system represents an advantage over previous delivery approaches, given that significant effects on macrophage polarization are observed at lower, controllable and safer doses (picograms to nanograms), compared to the high doses (nanograms to micrograms) of IL-4 used in previous studies [19, 21, 22].…”

Polyurethane for biomedical applications: A review of recent developments

“…As we already know from in vitro results that the surface plays a very important role in the bio-compatibility of polyurethanes, is it also true for in vivo ? The answer is yes according to Khandwekar's research, which demonstrated that surface entrapment technique could be used to modify/control the foreign body response on polyurethane surfaces (Khandwekar et al, 2010). Besides the basic research, a lot of polyurethane based medical devices were prepared and placed into animals for in vivo tests, which will be discussed below.…”

Electrospun poly(D,L)‐lactide nonwoven mats for biomedical application: Surface area shrinkage and surface entrapment

“…The dramatic decrease in contact angle suggests that hydrophilic PEG was indeed coated on the surface of the nanofibers. Compared with other surface modification methods, the result was better than plasma treatment (around 50 ) 42 and surface grafting with acrylic acid (40)(41)(42)(43)(44)(45) ). 43 The resultant hydrophilicity is crucial for future applications as biomedical materials.…”

“…This method can also be applied for surface engineering of other polymers, for example, polypropylene 39 and polyurethane. 40,41 After surface entrapment at 42 C, the PDLLA nanofiber mats shrunk to approximately 25% of their original size. Then the nonwoven mats were cut into 10 mm  10 mm specimens and immersed in Tris buffer at 37 C. Their size was measured at each time interval.…”