Inflammatory Problems with Implants

These fragments can be attacked by enzymes to produce lower molecular weight metabolites. Acid fragments that are produced during degradation of the polymer backbone have shown to cause local tissue inflammation (60). 

The inflammation has been observed in vascular systems as well and the extent of inflammation depends on the pH of the acid that in turn is dependent on the type and amoimt of acid produced during degradation. 

Such an inflammation is not typically observed in polymers that degrade by surface erosion, such as poly(orthoester)s and poly(an-hydride)s as the amount of acid released at a given time is small to cause tissue inflammation (60). 

1 Self-regulating System for Controlling the Acidic Effects 

A biodegradable material can be combined with a buffering agent (60). There, a second (another) biodegradable material is encapsulating the buffering agent. 

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Repeated episodes of catheter obstruction by fibrin clots or omental encapsulation can be a problem during continuous peritoneal insulin infusion from implanted pumps (SEDA 20, 397). In the encapsulated tissue, collagen fibrosis, inflammatory reactions with lymphocytes, and amyloid-like deposits reacting to anti-insulin antibodies can occur higher macrophage chemotaxis may also promote these processes. 

Biocompatibility is actually a major problem for implants and bioactive sol-gel glasses have been developed. They are typically made of a mixture of silica and calcium phosphate in order to show some affinity for the in vitro and in vivo nucleation of apatite (Hench, 1998). Such sol-gel glasses can also be used as implantable drug carriers. Experiments performed with ibuprofen, an anti-inflammatory drug, show that both processes, formation of an apatite layer and drug release, occur simultaneously. The release kinetics is mainly influenced by the solubility of the drug and the pore size of the bioglass (Ramila, 2003 Hall, 2003). 

Naltrexone in combination with lactide/glycolide copolymer has been investigated (83-87). Chiang (85) reported the clinical evaluations of a bead preparation containing 70% naltrexone and 30% of a 90 10 lactide/glycolide copolymer. Each subject received a 10-mg i.v. dose of naltrexone and a 63-mg dose by subcutaneous implantation of the beads. Average plasma naltrexone levels were maintained at 0.3-0.4 ng/ml for approximately 1 month. Two out of three subjects experienced a local inflammatory reaction at the site of implantation. This unexplained problem prevented further clinical testing of... 

Several implanted biosensors have been developed and evaluated in both animals and humans (see Chapter 4). Detection systems are based on enzymes, electrodes, or fluorescence. The most widely studied method is an electrochemical sensor that uses glucose oxidase. This sensor can be implanted intravenously or subcutaneously. Intravenous implantation in dogs for up to 3 months has demonstrated the feasibility of this approach. Alternatives to enzymes are being developed, including artificial glucose receptors. Less success has been achieved with subcutaneous implants. Implantation of a needle type of sensor into the subcutaneous tissue induces a host of inflammatory responses that alters the sensitivity of the device. Microdialysis with hoUow fibers or ultrafiltration with biologically inert material can decrease this problem. 

Problems associated with biodegradable stents, such as migration soon after implantation and sudden breakdown, are another important concern in designing stents [25, 26]. Isotalo et al. [27] compared the biocompatibility of two different designs of self-reinforced PLLA (SR-PLLA) urethral stents braided and traditional spiral, as well as the stainless steel stent in a rabbit model. They found that the disintegration of the braided SR-PLLA stent was more closely controlled than that of the spiral SR-PLLA stent. No differences in the histological analyses between the two SR-PLLA stents were found, whereas the metallic stents caused the strongest inflammatory reactions. 

CaP ceramics are characterized by low degradation rates, fragility, weak fatigue resistance and easy rupture, but good tissue compatibility and response [339]. Their ability to bond directly to the bone together with the lack of toxicity and inflammatory reaction in-vivo have made CaP ceramics attractive in the biomedical field. However, their slow biodegradability has raised issues about their use in some of its applications. The introduction of porosity by specific factors and cells is reported to address the problem [340]. the release of conjugated implants proceeds in a controlled manner after an initial burst release. 

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