Precisely defined fiber scaffolds with 40 μm porosity induce elongation driven M2-like polarization of human macrophages

Abstract

Macrophages are key players of the innate immune system that can roughly be divided into the pro-inflammatory M1 type and the anti-inflammatory, pro-healing M2 type. While a transient initial pro-inflammatory state is helpful, a prolonged inflammation deteriorates a proper healing and subsequent regeneration. One promising strategy to drive macrophage polarization by biomaterials is precise control over biomaterial geometry. For regenerative approaches, it is of particular interest to identify geometrical parameters that direct human macrophage polarization. For this purpose, we advanced melt electrowriting (MEW) towards the fabrication of fibrous scaffolds with box-shaped pores and precise inter-fiber spacing from 100 μm down to only 40 μm. These scaffolds facilitate primary human macrophage elongation accompanied by differentiation towards the M2 type, which was most pronounced for the smallest pore size of 40 μm. These new findings can be important in helping to design new biomaterials with an enhanced positive impact on tissue regeneration.

Development of a New Bone‐Mimetic Surface Treatment Platform: Nanoneedle Hydroxyapatite (nnHA) Coating

“…Melt electrowriting (MEW) is a recently developed 3D printing technology which overcomes the above limitations of FDM and electrospinning, being capable of fabricating and controlling the deposition of micrometer-scale fibers. [27][28][29] This facilitates the manufacture of complex fibrous microarchitectures [30][31][32][33][34] consistent with that seen in native extracellular matrix (ECM) including that of bone. We recently utilized MEW to fabricate scaffolds with bone inspired fiber diameters of 10 µm and investigated whether the fiber architecture in terms of degrees of alignment could influence stem/stromal cell behavior.…”

Polymers for Melt Electrowriting

“…Without question, the current gold standard polymer used for MEW is PCL. [11,16] In the literature, studies are performed with different designs including the typical box-structured scaffolds [16] or scaffolds for cell experiments [20][21][22] to more complicated designs like sinusoid structures with horizontal layer stacking, [23] tubes, [24,25] or a fiber-hydrogel composite with mechanical properties similar to that of a heart valve. [26]…”

“…As PCL is highlighted in several reviews on clinical translation of tissue engineering products, the transition from university-led research to application in the clinic is often negatively impacted by the need to repeat experiments with medical-grade polymers. In this instance, our understand- Measured as M w = 80 kDa [31] [ 11,16,12,20,[22][23][24]26, Sigma Aldrich Product number 440744 [46] M n = 80 × 10 3 [ 5,21,56,57] M n = 35 × 10 3 M w = 83 × 10 3 [ 13] M w = 45 kDa [58][59][60] M n = 45 × 10 3 [ 61] [ 5,13,21,[56][57][58][59][60][61] Capa 6400 M w ≈ 37 × 10 3 a) MFI = 40 b) [ 62,63] Capa 6430…”

“…There are many studies investigating the printing parameters or phenomena using PCL [13,11,16,67] so as to make different scaffold designs for biomedical applications. [3] This includes the standard box pore morphology scaffolds ( Figure 1C,D) or triangular pore scaffolds ( Figure 1E) that are followed by understanding how this influences cell morphology and cell adhesion, [20][21][22]31,46] including mathematical modeling of pore bridging dynamics. [66] However, more recently, complex designs or further improvements for specific applications are gaining more and more interest.…”

Harnessing Inorganic Nanoparticles to Direct Macrophage Polarization for Skeletal Muscle Regeneration

“…Regarding the impact mediated by material porosity, Tylek and colleagues recently exploited advanced melt electrowriting (MEW) to fabricate poly-ε-caprolactone (PCL)-based scaffold with box-shaped pores with various inter-fiber spacing, from 100 μm to 40 μm. The resulted scaffolds facilitated human primary macrophages elongation and polarization towards the M2 phenotype, with the smallest pore sized as the most effective [ 35 ]. Scaffold surface topography is widely recognized as modulator of the immune players; in the last decade, indeed, many studies highlighted the possibility to attenuate the inflammatory process and drive macropages towards the pro-healing phenotype [ 36 ], by controlling scaffold surface grooves and gratings—for example, via 3D lithographic methods.…”