Inherently Antimicrobial Biodegradable Polymers in Tissue Engineering

Abstract

Many of the strategies currently being explored in the field of tissue engineering involve the combination of cells and degradable engineered scaffolds for the regeneration of biological tissues. However, infection of the wound or the scaffold itself results in failure of healing. Therefore, a new area of development in the field is the synthesis of polymer-based scaffolds that inherently have the ability to resist microbial infection as degradation occurs and new tissue replaces the scaffold. These scaffolds, defined as inherently antimicrobial biodegradable polymers (IABPs), can be classified based on their monomeric components as follows: (1) traditional antimicrobials (such as beta-lactams, fluoroquinolones, glycopeptides, and aminoglycosides), (2) naturally derived compounds (such as extracellular matrix components, chitosan, and antimicrobial peptides), and (3) novel synthetic antimicrobials. After validation of chemical synthesis as well as physicochemical characterization of a newly created IABP, thorough in vitro and in vivo assays must be conducted to ensure antimicrobial efficacy as well as biocompatibility as a tissue-engineered scaffold system. In this review, we will introduce existing IABPs, discuss the current platforms that have been developed for the synthesis of IABPs, and highlight future directions as well as challenges in the field.

Advanced Strategies for Modulation of the Material–Macrophage Interface

“…The most common approach aims to kill bacterial cells present on the biomaterial surface with the incorporation of traditional antibiotics (beta-lactams, fluoroquinolones, glycopeptides, and aminoglycosides). [115] This can be achieved either through loading antibiotics in polymer systems and relying on the diffusion for local delivery [116] or covalently immobilizing the antibiotics and relying on polymer biodegradation to release the antibiotic, which may occur over an extended period of time. [115] However, as it is estimated that more than 80% of hospital infections involve biofilms, [117] which are less metabolically active and have higher resistance to antibiotics (up to 100-1000 times higher), [118] these approaches often have limited utility.…”

“…The most common approach aims to kill bacterial cells present on the biomaterial surface with the incorporation of traditional antibiotics (beta‐lactams, fluoroquinolones, glycopeptides, and aminoglycosides). [ 115 ] This can be achieved either through loading antibiotics in polymer systems and relying on the diffusion for local delivery [ 116 ] or covalently immobilizing the antibiotics and relying on polymer biodegradation to release the antibiotic, which may occur over an extended period of time. [ 115 ]…”

Drug delivery and tissue engineering to promote wound healing in the immunocompromised host: Current challenges and future directions

“…Poly(lactide-co-glycolide)(PLGA)/poly(lactide)-based microparticles, for example, were demonstrated to be capable of releasing biologically-active GM-CSF in a murine model at concentrations > 10 ng/mL for at least nine days and these microparticles resulted in local recruitment of neutrophils and macrophages at the site of injection [84]. Chitosan is another biomaterial that has been shown to sustain delivery of GM-CSF within murine models [86]; in addition to its ability to enhance GM-CSF local delivery, chitosan has the added benefit of inherent antimicrobial properties [87, 88]. Further work has been done to create chitosan-based microparticles for further control over delivery kinetics and deliver GM-CSF plasmid DNA [89].…”

“…To replace the infection-resistant function of the immune system, local delivery of antibiotics to treat or prevent infection has been a longstanding goal within the field with some success in translation of biomaterials-based products to market [126, 127]. Polymer-based delivery of antibiotics as well as the synthesis of inherently antimicrobial polymers and antifouling materials are areas that have been reviewed recently [87, 128, 129]. Emulsions and oils are other vehicles being explored that have inherent antimicrobial activity [130, 131].…”

Large Animal Models of an In Vivo Bioreactor for Engineering Vascularized Bone

“…While these scaffolds may lack some of the biological architecture and signals inherent to autologous bone, they offer other advantages such as tunable degradation properties and minimization of donor tissue. 29 Therefore, to determine the efficacy of synthetic ceramic graft in producing bone in the ovine in vivo bioreactor, different ratios of autologous graft and clinically-available biphasic ceramic graft (85% beta-tricalcium phosphate, 15% hydroxyapatite) were evaluated. 24 The ceramic scaffold was capable of supporting the growth of viable mineralized tissue the periosteum (Fig.…”