Determining the effect of a matrix metalloproteinase-inhibiting material on degradable biomaterial implants

Implanted tissue engineered constructs trigger a foreign body reaction (FBR). The FBR can diminish the construct's therapeutic effects. Matrix metalloproteinases (MMPs) are expressed in the FBR and are possible targets for control. It was hypothesized that a hydroxamate-based MMP-inhibiting (MI) polymer would alter the FBR to a degradable implant (construct) and delay its remodelling in vivo. Constructs were co-implanted subcutaneously in mice with MI polymer or poly(methyl methacrylate) controls. Visual, mass, volume and mechanical property data suggested MI polymer delayed construct remodelling. MI treatment appeared to reduce MMP-2 and -9 activities in the implant site at day 10. Surprisingly, MMP-2, -8, tissue inhibitor of metalloproteinase-I and inflammatory cell concentrations were higher with MI treatment. In this model and context, MI polymer appears pro-inflammatory and new methods for deploying the polymer should be explored. It was concluded that strategies focusing on inhibiting MMPs while ignoring their generation might not be successful.