6.2. Cell and soft tissue response to NiTi

The local tissue response is the most important aspect of biocompatibility (Vince et al. 1991). The cell and soft tissue responses to NiTi have not been elucidated in detail. The biocompatibility of a material in vivo can be evaluated by analyzing the cell population present, measuring the mediator and metabolite cells excreted, or analyzing the morphologic characteristics of the tissue around the implant (Hunt et al. 1993, Hunt et al. 1995, Anderson 1996, Anderson et al. 1996, Harada et al. 1996). If the material is clearly toxic, it induces a strong local response. Normal histological and morphological in vivo examinations with animals give reasonably reliable results and belong to the basic protocol used to estimate the biocompatibility of a new material. However, it must be kept in mind that if there are toxic elements in the material which dissolve slowly, they might give symptoms many years after implantation. When a material is intended for safe use inside the body, its in vivo performance and biocompatibility must be very well verified.

Based on a very small number of studies carried out earlier, it has been suggested that the biocompatibility of NiTi in muscle tissue is at least equivalent to Co-Cr and stainless steel alloys, and comparable to titanium (Cutright et al. 1973, Castleman et al. 1976). Pure nickel implanted intramuscularly has been found to cause severe local tissue irritation and necrosis (Laing et al. 1967). On the other hand, nickel-containing alloys are notably well tolerated. However, there has been a substantial lack of evidence on the biocompatibility of NiTi and the role of nickel in the alloy. Thus, the aim of the intramuscular implantation study was to clarify the detailed soft tissue response to NiTi.

The host reaction after implantation is not a normal wound-healing process. It has certain specific features that ultimately depend on the bulk material and its surface properties as well as on biomechanical considerations (Thomsen et al. 1991, Anderson et al. 1996). From the standpoint of biocompatibility, the important tissue reactions are mainly related to the inflammatory reaction (Anderson 1988). The general peri-implant soft tissue reaction that took place in the present study is shown in Figure 5-1.

Surgical trauma initiates an acute non-specific inflammation, which is characterized by vascular changes, including capillary dilatation, enhanced permeability and increased blood flow. The implant is surrounded by a blood clot containing white blood cells, erythrocytes, platelets and fibrin (Anderson et al. 1996).

Polymorphonuclear granulocytes, and later monocytes/macrophages, migrate into the damaged tissues, where their phagocytic activity removes tissue debris, deleterious foreign material and pathogens. The presence of phagocytes later than immediately after surgery may signify problems with the material, while a large number of neutrophils usually indicate infection. There were PMNs present in the NiTi capsule in the 2-week samples, and occasionally even in the 26-week samples, but similar findings were seen with stainless steel and Ti-6Al-4V materials.

The presence of lymphocytes may be anticipated in the cases where an immune response or type IV hypersensitivity reaction has occurred (Thomsen et al. 1991). Lymphocytes can be discerned by typical morphology, but the identification of different lymphocyte cell types is not possible with conventional microscopy and stainings. Furthermore, we cannot say much about their functional activity. The numbers of such cells observed in this study were, however, similar in all the materials.

Monocytes migrate to peripheral tissues, where they assume the role of macrophages (Burkitt et al. 1993). Macrophages play a very important role in acute inflammation and probably in final biocompatibility (Anderson et al. 1984). They may release mediators, which can, in turn, activate other cells. Macrophages are found to affect such processes as fibroblast and lymphocyte activity, the complement system and angiogenesis (Anderson 1988, Bonfield et al. 1991). The amounts of macrophages at different time points did not reflect differences between the materials tested.

Macrophages form multinucleated foreign body giant cells (Murch et al. 1982). The presence of these cells is significant, because they represent a specific inflammatory response evoked by the foreign substance (Thomsen et al. 1991). The giant cells were very few in number, and most were present together with the previously mentioned ring-shaped debris particles. Judging by the giant cells, NiTi is well tolerated.

Fibroblasts migrated to the injury site in the early phase of healing and gathered around the implants. Other granulation tissue was slowly replaced by fibroblast proliferation and collagen deposition. In optimal situations, the inert biomaterial forms a thin, relatively avascular and acellular fibrous scar capsule at the interface (Williams 1986). Such capsules were present with the NiTi implant capsules, demonstrating good acceptance.

After implantation, a number of cellular and humoral factors, such as chemotactic and growth factors, complement, cytokines, hormones, enzymes, adhesion molecules and a large number of other factors may be involved in the deleterious soft tissue reaction (Anderson 1988, Tsunawaki et al. 1988, Bonfield et al. 1991, Cardona et al. 1992, Tang et al. 1996). The long-term result of how an implant is accepted is the result of all these variables. The findings of this study support NiTi as being equally good as stainless steel and Ti-6Al-4V when implanted in muscular tissue. The results are in agreement with some earlier studies that complement them. To determine the final consequences of the biocompatibility of Nitinol, it may be necessary to analyze more cellular factors involved in the long-term implantation process.