Biomaterials/tissue interactions: possible solutions to overcome foreign body response

Abstract

In recent years, a variety of biomaterial implantable devices has been developed. Of particular significance to pharmaceutical sciences is the progress made on the development of drug/implantable device combination products. However, the clinical application of these devices is still a critical issue due to the host response, which results from both the tissue trauma during implantation and the presence of the device in the body. Accordingly, the in vivo functionality and durability of any implantable device can be compromised by the body response to the foreign material. Numerous strategies to overcome negative body reactions have been reported. The aim of this review is to outline some key issues of biomaterial/tissue interactions such as foreign body response and biocompatibility and biocompatibility assessment. In addition, general approaches used to overcome the in vivo instability of implantable devices are presented, including (a) biocompatible material coatings, (b) steroidal and nonsteroidal anti-inflammatory drugs, and (c) angiogenic drugs. In particular, strategies to overcome host response to glucose biosensors are summarized.

Fig. 1

Sequence of events involved in the FBR to an implantable device. Note that overlap and simultaneous occurrence of these events occurs (based on (21,33))

Fig. 2

Pharmacodynamic changes in representative tissue sections on day 3 from s.c. tissue of rats implanted with PLGA microsphere/PVA hydrogel composites: a without dexamethasone and b with dexamethasone compared with control untreated tissue sections (c). Inflammation-mediating cells and normal cells are stained purple and pink, respectively (hematoxylin and eosin stain). Hydrogel composites are marked HC

Fig. 3

Pharmacodynamic changes in representative tissue sections on day 21 from s.c. tissue of rats implanted with PLGA microsphere/PVA hydrogel composites: a without dexamethasone and b with dexamethasone. Inflammation-mediating cells and normal cells are stained purple and pink, respectively (hematoxylin and eosin stain). The white area surrounding the hydrogel composite in b is an artifact due to tissue detachment during sectioning. Hydrogel composites are marked HC

Fig. 4

Pharmacodynamics changes in representative subcutaneous tissue sections of rats implanted with PLGA microsphere/PVA hydrogel composites (asterisk) containing VEGF alone over week 1 (a), week 2 (b), week 3 (c), and week 4 (d) postimplantation and dexamethasone and VEGF combination week 1 (e); week 2 (f); week 3 (g), and week postimplantation (h). Inflammation-mediating cells and normal cells are stained purple and pink, respectively (hematoxylin and eosin stain)