Abiotic/Biotic Interface Workshop

1. Abiotic/Biotic Interface Workshop NIH April 8, 2009

2. Introduction • The NIH Nano Task Force and the NIH Nanomedicine Roadmap Initiative sponsored a workshop on the Abiotic/biotic Interface at NIH on April 8, 2009. Panelists presented findings from their recent research regarding manipulation of the surface properties of materials and cellular responses. • This report as organized as a Powerpoint presentation with edited versions of the panelists presentations following an Executive Summary

3. Foreign Body Response • Many engineered biomaterials elicit similar magnitude of foreign body responses as do conventional materials. • This response occurs in a rather stereotyped fashion and appears to be highly determined by rapid adsorption of proteins to the implant surface that results in recruitment of a large repertoire of cellular responses culminating in an interfacial layer of macrophages and macrophage-dependent foreign body giant cells surrounded by a fibrous capsule.

4. Potential for Modification • Recent work from a number of laboratories indicates that the function of the immune synapse and the proliferation of stem cells can be modulated by manipulation of the mechanical properties of the surrounding extracellular matrix at the nanoscale. • Thus, it is possible that the kinetics and the magnitude of the in vivo foreign body response to implanted materials might be modulated through manipulations of surface properties at the nanoscale.

5. Research Program • Systematic exploration of the potential design space of material surface properties comparing macro- to micro- to nano-material length scales in both 2D and 3D systems, surface pattern and nanotopological influences, and their effects on mixed protein adsorption/desorption and subsequent cellular adhesion, differentiation, juxtacrine and paracrine communication, activation, apoptosis, and proliferation are needed to develop design principles for improved implantable materials and surfaces. • Research teams should include investigators with expertise in materials and interfacial science, and in the in vitro and in vivo pathology and immunology of the foreign body response.

6. Standards • While standards for biocompatibility testing for biomaterials have been published, these are neither uniformly applied to biomaterials analysis nor uniformly interpreted, and certainly difficult to apply to nanomaterials assessments. • High-throughput physiological and toxicological screening methods should be developed for first-pass biocompatibility evaluation of the enormous number of potential materials that can be designed and synthesized to interface with biological systems. • Standard assay procedures for relevant prolonged (> 21 days) in vitro biocompatibility testing and validation and demonstration of their accurate prediction of in vivo host responses need to be developed.

7. Presentations Basic Science • State of the field: David Grainger, U. Utah abiotic.grainger.ppt • Pathology of the foreign body response: James Anderson, Case abiotic.anderson.ppt • Physiology of force and shear at the nanoscale: Peter Davies, U. Penn abiotic.davies.ppt • Nanoscale surfaces to control stem cell function: Kevin Healey, Berkeley abiotic.healey.pdf • Immune regulation by force at the nanoscale: Michael Dustin, NYU abiotic.dustin.ppt Clinical Applications and Needs • Bioelectric Interfaces at the Nanoscale: Dustin Tyler Columbia abiotictyler.ppt • Osseointegrated Prostheses, Gordon Blunn: University College, London abiotic.blunn.ppt • Implantable Artificial Kidney: Shuvo Roy, U. Michigan abiotic.roy.ppt