Long- and short-term effects of biological hydrogels on capsule microvascular density around implants in rats

Abstract

Fibrous capsule formation around implants can inhibit solute exchange between implantable devices and the circulation. Parylene-n coated polycarbonate disks surrounded with growth factor reduced Matrigel (MG) or several gelatin-based matrices were implanted intramuscularly into rats for 21 or 50 days. MG supplemented with vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) increased capsule microvascular density at 21 days (p < 0.05) when compared to bare parylene-coated polycarbonate disks (control). The increased microvascular density around VEGF- and bFGF-treated implants regressed by 50 days and was no longer significantly different from controls. The microvascular density induced by the gelatin-based matrices was not significantly different from controls at 21 days, but was increased at 50 days (p < 0.05), suggesting a slower, long-term effect. Disks treated with MG and gelatin-based matrices had thinner capsules at 21 days (p < 0.05). By 50 days, the capsule thicknesses around these implants were no longer statistically thinner than controls. The capsule thickness around implants treated with VEGF, bFGF, and essential gelatin-based matrix was thinner than controls at 50 days (p < 0.05). These results indicate that it is possible to increase functional microvascular density within fibrous capsules using angiogenic growth factors and gelatin-based matrices. However, this effect may be short-lived, requiring chronic administration of growth factors.

The effect of phosphorylcholine‐coated materials on the inflammatory response and fibrous capsule formation: In vitro and in vivo observations

“…In many cases, however, fibrous capsule can lead to device failure, for interference in the osseointegration process, 15 causing poor tissuedevice contact that may also lead to infection, 16 or restriction of nutrient supply to and from the device. 17 A multitude of studies have been performed with different biocompatible medical implants, comparing different biomaterials, their sizes, surface morphologies, and implantation sites. It is generally believed that the ideal biomaterial would be one that can limit long-term foreign stimuli, and hence limit the progression of acute to chronic inflammation and reduce fibrous capsule formation.…”

Biomaterials/Tissue Interactions: Possible Solutions to Overcome Foreign Body Response

“…These methods offer the advantage of being very similar to macromolecular substances that the biological environment is prepared to recognize and to deal with metabolically. On the other hand, serious disadvantages are (a) natural polymers are frequently immunogenic, (b) these polymers typically decompose or undergo pyrolytic modification at temperatures below their melting point, thereby precluding the convenience of high-temperature thermoplastic processing methods (such as melt extrusion) during the manufacturing of the implant, and (c) since they are derived from animal or plant sources, natural variability in (63,64). These include poly(hydroxyl ethyl methacrylate) (59), PEG (60), and PVA (65)(66)(67)(68)(69)(70)(71)(72)(73)(74).…”

Controlling fibrous capsule formation through long-term down-regulation of collagen type I (COL1A1) expression by nanofiber-mediated siRNA gene silencing

“…While the modification of material surface chemistry/physics [9–12] and the incorporation of biological factors and proteins [13–17] have been developed to improve the biocompatibility of implanted devices, several potential drawbacks have also been reported. The use of a hydrogel-type coating, for instance, may display poor adhesion to the substrate, unacceptable mechanical properties for some applications and pose potential safety issues due to the use of chemical cross-linking agents [9, 16]. The administration of anti-inflammatory agents, such as dexamethasone, while being able to minimize implantation-associated inflammation, can inhibit endogenous blood vessel growth [17, 18], thereby decreasing blood circulation surrounding the implant [15].…”