Reduction of implant infection via tunable stimulation of localized adaptive immune response

Abstract

Compositions, implantation devices and methods for stimulating an immune response to infection are discussed. In some examples, the compositions, implantation devices or methods of regulating the amplification of an adaptive immune response to infection involves use of one or more particles locally at a surgical or implant site to control bacterial infections without detrimental systemic side-effects. In some examples, the particles can be coated or layered onto the surface of an implantable device or material. In other examples, the particles can be injected into the site of implantation.

Description

[0001]This application is a divisional of U.S. patent application Ser. No. 14,347,551, filed Mar. 26, 2014, which is a U.S. National Stage Application filed under 35 U.S.C. § 371 from International Application Serial No. PCT / US2012 / 057194, filed Sep. 26, 2012, which claims benefit of the priority filing date of U.S. Provisional Patent Application Ser. No. 61 / 539,282, filed Sep. 26, 2011, the contents of which are specifically incorporated herein in their entirety.BACKGROUND[0002]Implanted medical devices or biomaterials can present microenvironments that are conducive to bacterial colonization or infection. Such infections can require repetitive hospital visits or can even require removal or replacement of the implanted device or material. For example, approximately 1 million inguinal and 20,000 ventral herniorrhaphies are performed yearly in the United States. It is estimated that approximately 3 to 8 percent of patients who undergo such surgery develop post-operative infections. T...

AI Technical Summary

Benefits of technology

The invention is a composition that can be applied to treat microbial infections in animals. The composition contains particles with a particular size range. When administered to the site of infection, the composition can reduce the amount of bacteria there by at least 30%, 40%, 50%, 60%, 70%, 80%, or 90%.

Problems solved by technology

Such infections can require repetitive hospital visits or can even require removal or replacement of the implanted device or material.

These types of infections can cause complications that require longer post-surgery care and escalate health care costs.

Overall surgical implant infections costs have been credited with increasing direct medical costs by more than $3 billion annually in the US.

In addition to the financial burden caused by repetitive implant surgery and longer inpatient hospital stays, infections can be fatal or near fatal to a significant portion of patients.

At least some degree of bacterial entry into a surgical site is nearly unavoidable at the time of surgery.

However, the presence of an implant can complicate the clearance of bacteria from the surgical site.

If bacterial colonization occurs on the surface of the implant, traditional means of treatment including the use of systemic antibiotics, are largely unsuccessful in treating the infection.

Existing technologies fail to address the underlying impairment of the local cell mediated immune response.

Accordingly, patients, including immune-compromised individuals, remain exceedingly difficult to treat successfully.

Although neutrophils are important in fighting infection, they can promote tissue damage.

For example, neutrophils can cause significant damage at healthy tissue sites by releasing toxic substances at a vascular wall or uninjured tissue.

Initiation of an infection occurs when the infecting organism is pathogenic, and the host is susceptible to pathogenic invasion.

Further, bacteria encased in a biofilm often cannot be cleared or eliminated by macrophages.

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