title: Long-term sustained release of salicylic acid from cross-linked biodegradable polyester induces a reduced foreign body response in mice.
abstract: There has been a continuous surge toward developing new biopolymers that exhibit better in vivo biocompatibility properties in terms of demonstrating a reduced foreign body response (FBR). One approach to mitigate the undesired FBR is to develop an implant capable of releasing anti-inflammatory molecules in a sustained manner over a long time period. Implants causing inflammation are also more susceptible to infection. In this article, the in vivo biocompatibility of a novel, biodegradable salicylic acid releasing polyester (SAP) has been investigated by subcutaneous implantation in a mouse model. The tissue response to SAP was compared with that of a widely used biodegradable polymer, poly(lactic acid-co-glycolic acid) (PLGA), as a control over three time points: 2, 4, and 16 weeks postimplantation. A long-term in vitro study illustrates a continuous, linear (zero order) release of salicylic acid with a cumulative mass percent release rate of 7.34 × 10(-4) h(-1) over ∼1.5-17 months. On the basis of physicochemical analysis, surface erosion for SAP and bulk erosion for PLGA have been confirmed as their dominant degradation modes in vivo. On the basis of the histomorphometrical analysis of inflammatory cell densities and collagen distribution as well as quantification of proinflammatory cytokine levels (TNF-α and IL-1β), a reduced foreign body response toward SAP with respect to that generated by PLGA has been unambiguously established. The favorable in vivo tissue response to SAP, as manifest from the uniform and well-vascularized encapsulation around the implant, is consistent with the decrease in inflammatory cell density and increase in angiogenesis with time. The above observations, together with the demonstration of long-term and sustained release of salicylic acid, establish the potential use of SAP for applications in improved matrices for tissue engineering and chronic wound healing.
authors.affiliation: Laboratory for Biomaterials, Materials Research Centre, ‡Department of Chemical Engineering, §Bioengineering Program, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Yashoda
authors.initials: Y
authors.lastname: Chandorkar
authors.forename: Nitu
authors.initials: N
authors.lastname: Bhaskar
authors.forename: Giridhar
authors.initials: G
authors.lastname: Madras
authors.forename: Bikramjit
authors.initials: B
authors.lastname: Basu
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D005549:Foreign-Body Reaction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D020156:Salicylic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D011091:Polyesters; D020156:Salicylic Acid