Salicylic acid (SA)‐eluting bone regeneration scaffolds with interconnected porosity and local and sustained SA release

Abstract

In previous work, we observed that localized and sustained delivery of an anti-inflammatory drug, salicylic acid (SA), via a SA-based polymer (SAP) powder significantly enhanced diabetic bone regeneration through long-term mitigation of local inflammation. In this study, SAP was formulated into uniform microspheres and then sintered into a scaffold with an interconnected porous structure and modulus suitable for bone regeneration. The SAP scaffolds have ∼45% SA loading, which is the highest among drug-eluting bone regeneration scaffolds to-date. In addition, the scaffold provides localized, controlled and sustained SA release that has been proven to enhance diabetic bone regeneration. With the combination of physical (interconnected porosity) and chemical therapeutic features (high drug loading and sustained release), the novel SAP scaffolds offer unique therapeutic advantages and are promising diabetic bone regeneration candidates. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 311-318, 2017.

4D Printable Salicylic Acid Photopolymers for Sustained Drug Releasing, Shape Memory, Soft Tissue Scaffolds

“…As expected, variation of the NaOH concentration could be used to vary mass loss in all species, which indicates that the degradation mechanism is purely hydrolytic (Figure , SI Figure 24). Most importantly, by these degradation studies we confirmed the release of salicylic acid derivatives in all cases through spectroscopy, with more prolonged release demonstrated by our materials compared with other PolyAspirins and encapsulated/incorporated forms of salicylic acid. ,,− ,, The degradation also follows a surface erosion process, as confirmed through optical observations of film erosion (SI Figure 25) as well as of porous structures over time as well as through more complex drug release studies. Through selection of the linker species, the daily released concentration could be varied while maintaining linear release profiles over time.…”

“…Several studies have used salicylic acid as building blocks for either soft thermoset materials displaying low strains at failure of approximately 20% during uniaxial tensile testing or functional polymers with temporal components in their design (4D polymers). ,− Notably, the Uhrich group has contributed a large body of work developing PolyAspirin, attempting to leverage polymer design to overcome the aforementioned drug delivery loading limitations where salicylic acid is directly incorporated into the polymer backbone to serve as a therapeutic agent upon release. ,,,, While the release profiles of this work are promising with regard to sustained release greater than 24 h and ∼45% loading of the salicylic acid (the highest to date), a significant limitation with this technique is the difficulties with processing these materials into geometries which may be of clinical use and extending the release times past ∼60 days. ,,, Recently, this work has focused on making the materials more processable, including developing extrudable formulations, which unfortunately required lowered the salicylic acid concentration in the polymer backbone to achieve greater flow . Other attempts at incorporating salicylic acid have focused on leveraging salicylic acid in the polymer backbone.…”

Spatiotemporal Management of the Osteoimmunomodulation of Fibrous Scaffolds by Loading a Novel Amphiphilic Nanomedicine

“…Loading immunomodulatory agents is a simple and promising strategy, but the improper release behavior would lead to adverse effects. 19,20 For instance, the method of directly loading anti-inflammatory drugs suffers from the problems of initial burst release and short release term. 21,22 The initial burst release might overinhibit the activation of M1 phenotype macrophage, which is detrimental to tissue regeneration.…”

“…Loading immunomodulatory agents is a simple and promising strategy, but the improper release behavior would lead to adverse effects. , For instance, the method of directly loading anti-inflammatory drugs suffers from the problems of initial burst release and short release term. , The initial burst release might overinhibit the activation of M1 phenotype macrophage, which is detrimental to tissue regeneration. , The short release period determines that these systems can relieve only the initial acute inflammation, but lose protection against later degradation-induced chronic inflammation. , As an alternative, a series of prodrugs with inflammation-responsive release property have been synthesized to achieve full-course inhibition of degradation induced inflammation. , However, because of the “shielding effect” of the substrate, although drug release can match the later degradation-induced chronic inflammation, drug release may be insufficient to relieve the initial acute inflammation in the early phase of degradation, resulting in delayed activation of M2 phenotype macrophages. , Precise control on the transition from inflammation phase to anti-inflammation phase is still a huge challenge for the developing of advanced bone tissue scaffolds …”

Biomedical Applications of Nanotechnology and Nanomaterials

“…These bioactive shells have inherent targeting properties that can be tuned for targeted drug delivery to treat cancer, and block scavenger receptors to inhibit artherosclerosis, Parkinson’s, and other diseases with similar pathophysiology [ 14 , 15 ]. In addition to the aforementioned biomedical applications of bioactive polymers, they have implications to engineer biodegradable and bioactive sutures and dressings, drug eluting stents and scaffolds, and medical devices with anti-microbial properties to prevent bio-fouling [ 16 , 17 , 18 ]. In the last decade or so, we witnessed a spurring growth in biomedical applications of inorganic nanomaterials.…”