Foreign body reaction to biomaterials.

An appropriate cellular response to implanted surfaces is essential for tissue regeneration and integration. It is well described that implanted materials are immediately coated with proteins from blood and interstitial fluids, and it is through this adsorbed layer that cells sense foreign surfaces. Hence, it is the adsorbed proteins, rather than the surface itself, to which cells initially respond. Diverse studies using a range of materials have demonstrated the pivotal role of extracellular adhesion proteins--fibronectin and vitronectin in particular--in cell adhesion, morphology, and migration. These events underlie the subsequent responses required for tissue repair, with the nature of cell surface interactions contributing to survival, growth, and differentiation. The pattern in which adhesion proteins and other bioactive molecules adsorb thus elicits cellular reactions specific to the underlying physicochemical properties of the material. Accordingly, in vitro studies generally demonstrate favorable cell responses to charged, hydrophilic surfaces, corresponding to superior adsorption and bioactivity of adhesion proteins. This review illustrates the mediation of cell responses to biomaterials by adsorbed proteins, in the context of osteoblasts and selected materials used in orthopedic implants and bone tissue engineering. It is recognized, however, that the periimplant environment in vivo will differ substantially from the cell-biomaterial interface in vitro. Hence, one of the key issues yet to be resolved is that of the interface composition actually encountered by osteoblasts within the sequence of inflammation and bone regeneration.

Mediation of Biomaterial–Cell Interactions by Adsorbed Proteins: A Review

Immune responses to implants – A review of the implications for the design of immunomodulatory biomaterials

Quartz crystal microbalance: a useful tool for studying thin polymer films and complex biomolecular systems at the solution-surface interface.

Advancing dental implant surface technology--from micron- to nanotopography.

Today, aseptic loosening is the most common cause of revision of major arthroplasties. Aseptic loosening accounts for more than two-thirds of hip revisions and almost one-half of knee revisions in Sweden. Several theories on the cause of aseptic loosening have been proposed. Most of these theories, however, are based on empiric observations, experimental animal models or anecdotal cases. In this review, we discuss the most common theories concerning aseptic loosening. It emerges from this review that aseptic loosening has a multifactorial etiology and cannot be explained by a single theory.

https://www.tandfonline.com/doi/pdf/10.1080/17453670610045902

Aseptic loosening, not only a question of wear: a review of different theories.

The inflammatory and fibrous responses in a subcutaneous rat model were evaluated around degradable polyurethane urea (PUUR; Artelon), with titanium and tissue culture polystyrene (PS) discs having different surface chemical properties but similar surface topography. Cytokines, viability, cellular response, differentiation of cells and fibrous capsule formation and vascularization was investigated after 1, 7 and 21 days of implantation. The exudates retrieved from the pockets were analysed with respect to the total cell numbers, the proportions of cell types, the differentiation of monocytes/macrophages (ED1, ED2), the DNA content and the viability (LD, Trypan blue). Tumour necrosis factor alpha ((h)TNF-alpha) and interleukin-10 ((h)IL-10) were quantified by ELISA. The number of blood vessels, blood vessel luminal area, blood vessel distribution and the fibrous capsule thickness were analysed. The highest number of cells in the exudates around all implants was detected during the early phase of healing (1-7 days). The proportion of ED2-positive cells in the exudates increased from 2-8% at 1 day to 43-56% at 21 days. The levels of TNF-alpha were low with a decrease at 7 days. After 21 days high amounts of IL-10 in the exudates were detected, in particular around PUUR. This study shows that the transition from inflammation to repair (1-21 days) around PUUR, Ti and PS materials was characterized by a decrease in inflammatory cell influx, an increasing proportion of ED2-expressing macrophages, a biphasic TNF-alpha secretion, an increase of IL-10 and a fibrous capsule formation similar to all materials tested.

The inflammatory cell influx and cytokines changes during transition from acute inflammation to fibrous repair around implanted materials.

The anti-inflammatory effects of the amide local anaesthetics lidocaine and bupivacaine were evaluated in vitro by examination of the metabolic activation and secretory responses of human polymorphonuclear granulocytes (PMNGs) and mononuclear cells. Pretreatment with lidocaine or bupivacaine had a dose-dependent inhibitory effect on PMNG luminol-amplified chemiluminescence stimulated by bovine serum albumin (BSA)/anti-BSA immune complexes (IC) or by serum-opsonized zymosan (SOZ) particles. Both lidocaine and bupivacaine inhibited the release of the inflammatory mediators leukotriene B4 (LTB4) and interleukin-1 (IL-1) evaluated by radioimmunoassay (RIA). Pretreatment of suspended PMNGs and monocytes with the anaesthetics caused a marked inhibition of LTB4 release when the cells were stimulated with SOZ. In short-term (24 h) cultures of mononuclear cells the addition of lidocaine or bupivacaine reduced, in a dose-dependent manner, the level of IL-1 detected after stimulation with lipopolysaccharide (LPS). In all three assays (chemiluminescence, LTB4 and IL-1 RIA) bupivacaine was found to be more potent than lidocaine. The present results show that amide local anaesthetics have marked suppressive effects on the metabolic activation and secretory functions of leukocytes stimulated by different agonists. Although the detailed mechanisms for these effects are not known, they may explain part of the potent anti-inflammatory actions of local anaesthetics previously described in vivo.

Inhibitory effects of amide local anaesthetics on stimulus‐induced human leukocyte metabolic activation, LTB4 release and IL‐1 secretion in vitro

An understanding of the biological response at material surfaces is a key biomaterials research area. Inflammation, tissue repair and regeneration are hallmarks of this response. Macrophages are long-lived and versatile cells and have a pivotal role at surfaces of implanted medical devices. The present review provides an update on macrophage behaviour at material surfaces. The interactions between cells and material surfaces are dynamic processes which require additional experimental models with different degrees of environmental complexity. It is concluded that both modifications of material surface properties and cellular signalling pathways will provide strategies for optimising the performance of biomedical devices.

Christina Gretzer

Papers

Aseptic loosening, not only a question of wear: a review of different theories.

The inflammatory cell influx and cytokines changes during transition from acute inflammation to fibrous repair around implanted materials.

Inhibitory effects of amide local anaesthetics on stimulus‐induced human leukocyte metabolic activation, LTB4 release and IL‐1 secretion in vitro

Macrophage interactions with modified material surfaces

Preparation of multilayer plasma protein films on silicon by EDC/NHS coupling chemistry