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.

Nanoparticle delivery of miR-223 to attenuate macrophage fusion

“…Recent studies focus on creating novel materials for implants, various polymer coatings, or change to the physical structure of the implant to circumvent this issue. For example, in attempt to create novel biopolymers with increased in vivo compatibility, Chandorkar et al fabricated a biodegradable salicylic acid releasing polyester that, when implanted subcutaneous (SC) in mice, reduces the FBR compared to a poly(lactic-co-glycolic acid) (PLGA) polymer [4]. Likewise, Udpa et al utilized chitosan coatings on propylene mesh in a rat abdominal wall model of hernia repair to compare the biocompatibility to currently available commercial meshes [5].…”

Self‐synthesized extracellular matrix contributes to mature adipose tissue regeneration in a tissue engineering chamber

“…12 An exogenous scaffold has been used in several studies, involving materials such as poly-lactic-co-glycolic acid (PLGA) and matrigel, 11,13 which may be associated with additional health risks. 14,15 However, adipose tissue can also be generated without an exogenous scaffold. 10 In the present study, we hypothesized that the adipose tissue flap in the TEC could generate its own scaffold during the incubation period, and the self-synthesized ECM may play a similar role as an exogenous scaffold.…”

“…However, for adipose tissue engineering, an appropriate extracellular matrix (ECM) may be required to support cell attachment, proliferation, and differentiation until the adipocytes can secrete their own ECM . An exogenous scaffold has been used in several studies, involving materials such as poly‐lactic‐co‐glycolic acid (PLGA) and matrigel, which may be associated with additional health risks . However, adipose tissue can also be generated without an exogenous scaffold .…”

Application of 3D printing technology in bone tissue engineering

“…Good biocompatibility requires that the scaffold material has good surface physicochemical properties to ensure normal adhesion and growth of the cells; the scaffold does not cause inflammatory reaction, any immunogenicity and cytotoxicity, and the degradation rate should be related to tissue growth. The speed is consistent, achieving a smooth transition from the stent to the ontogenesis [9,10]. In addition, during the degradation of the scaffold, the tissue cells are provided with a constantly changing interface for adhesion and growth, which contributes to the firm adhesion of the cells to the material.…”