Scaffold-based anti-infection strategies in bone repair

Abstract

Bone fractures and non-union defects often require surgical intervention where biomaterials are used to correct the defect, and approximately 10% of these procedures are compromised by bacterial infection. Currently, treatment options are limited to sustained, high doses of antibiotics and surgical debridement of affected tissue, leaving a significant, unmet need for the development of therapies to combat device-associated biofilm and infections. Engineering implants to prevent infection is a desirable material characteristic. Tissue engineered scaffolds for bone repair provide a means to both regenerate bone and serve as a base for adding antimicrobial agents. Incorporating anti-infection properties into regenerative medicine therapies could improve clinical outcomes and reduce the morbidity and mortality associated with biomaterial implant-associated infections. This review focuses on current animal models and technologies available to assess bone repair in the context of infection, antimicrobial agents to fight infection, the current state of antimicrobial scaffolds, and future directions in the field.

Figure 1. Bacterial adhesion and biofilm development

Biofilm formation begins by bacteria adhering and growing on a surface. As the pathogen continues to replicate a polysaccharide matrix is deposited. This matrix protects the pathogen from the host immune system and increases the development of antibiotic resistance.

Figure 2. Critically-sized non-union bone defects are used to assess the therapeutic efficacy of regenerative scaffolds

Contamination of these defects can be introduced before or after the scaffold is placed to establish the infection. Absence of antimicrobial agents will lead to the development of osteomyelitis, which is characterized by bone resorption and reactive bone formation. Infection resistant scaffolds are designed to prevent initial bacterial colonization whereas infection fighting scaffolds can be used to resolve an established biofilm and promote defect repair.

Figure 3. Scaffold based drug delivery for tissue repair

Current regenerative medicine strategies focus on delivering therapeutics to drive cell recruitment and tissue repair. As cells are recruited the scaffold degrades, releasing therapeutics, and promoting integration. Next generation biomaterials will include abilities to prevent or eliminate pathogens and provide regenerative cues.