Introducing Metal–Organic Frameworks to Melt Electrowriting: Multifunctional Scaffolds with Controlled Microarchitecture for Tissue Engineering Applications

Abstract

Scaffolds with multiple advantageous biological and structural properties are still a challenge in the field of tissue engineering. The convergence of advanced fabrication techniques and functional materials is key to fulfill this need. Melt electrowriting (MEW) is an additive manufacturing technique that enables the fabrication of microfibrous scaffolds with precisely defined microarchitectures. Here, it is proposed to exploit metal–organic frameworks (MOFs) to efficiently introduce multifunctionalities by combining polycaprolactone (PCL), the gold standard material in MEW, with a silver‐/silver‐chloride‐decorated iron‐based MOF (NH2‐MIL‐88B(Fe)). This results in highly ordered constructs with antibacterial properties and magnetic resonance imaging (MRI) visibility. Scaffolds with up to 20 wt% MOF are successfully melt‐electrowritten with a fiber diameter of 50 µm. Among these, 5 wt% MOF proves to be the optimal concentration as it exhibits silver‐induced sustained antibacterial efficacy while maintaining PCL cytocompatibility and in vitro immune response. The iron component of the MOF (Fe(III) nodes) renders the composite visible with MRI, thereby enabling scaffold monitoring upon implantation with a clinically accepted method. The combination of MEW and MOFs as tunable additives and cargo carriers opens the way for designing advanced multifunctional scaffolds with a wide range of applications in, e.g., tissue engineering, biosensing and drug delivery.

Application of metal-organic frameworks-based functional composite scaffolds in tissue engineering

“…ZIF-8 nanoparticles were added to molten PCL, and then 3D printing was used to successfully construct a ZIF-8-modified PCL bone repair scaffold [ 71 ]. Recently, a silver-/silver-chloride-decorated iron-based MOF (NH 2 -MIL-88B(Fe)) was introduced into PCL by melt electrowriting to construct highly ordered scaffolds with antibacterial properties and magnetic resonance imaging (MRI) visualization ability [ 80 ]. These multifunctional scaffolds have great potential for tissue engineering because they reduce the risk of postoperative infections and enable noninvasive monitoring after implantation.…”

Materials and Strategies to Enhance Melt Electrowriting Potential

“…With the focus on antibacterial properties, Mansi and co‐workers explored recently the incorporation of silver‐decorated iron‐based MOFs (NH 2 ‐MIL‐88B(Fe)). [ 88 ] High‐quality scaffolds with up to 20 wt% of MOF were successfully fabricated with a medium fiber diameter of 50 µm. Among these, 10 and 20 wt% samples showed a cell viability below 70% thus 5 wt% of MOF results the optimal concentration as it already exhibits silver‐induced excellent antibacterial efficacy while maintaining PCL cytocompatibility.…”

The Past, Present, and Future of Tubular Melt Electrowritten Constructs to Mimic Small Diameter Blood Vessels – A Stable Process?

“…PCL = poly‐Caprolactone, PP = Polypropylene, TPU = thermoplastic polyurethane, PLA = polylacticacid, GelNOR = gelatin‐norbonene, PLCL = Poly (L‐lactide‐co‐caprolactone), sP(EO‐stat‐PO) = six‐arm star‐shaped NCO‐ poly(ethylene oxide‐stat‐propylene oxide), PGS = poly(glycerol sebacate), MOF = Metal‐organic framework. References used in the Figure: Akentjew et al, [ 29 ] Jungst et al, [ 37 ] Hochleitner et al, [ 42 ] Zhang et al, [ 44 ] Gruber et al, [ 45 ] Skylar‐Scott et al, [ 46 ] Lyons et al, [ 47 ] Apsite et al, [ 48 ] Li et al, [ 49 ] Wunner et al, [ 50 ] Mansi et al, [ 51 ] Bertlein et al, [ 52 ] Castilho et al, [ 53 ] Brown et al, [ 54 ] Federici et al, [ 55 ] Pien et al, [ 56 ] Van Genderen et al, [ 57 ] Mueller et al [ 58 ]…”

“…It is relatively inert for cell attachment due to its hydrophobicity, making it not ideal as a direct cell seeding surface without modification. [ 55 ] Further, its mechanical properties lean more toward plastic deformation under stress in bulk, which would lead to a quick loss of mechanical strength under higher stresses. [ 55 ] Materials that feature better cell compatibility and more elastic mechanical characteristics while also matching its other beneficial properties would be ideal candidate for manufacturing of medical constructs with MEW.…”

“…PCL = poly-Caprolactone, PP = Polypropylene, TPU = thermoplastic polyurethane, PLA = polylacticacid, GelNOR = gelatin-norbonene, PLCL = Poly (L-lactide-co-caprolactone), sP(EO-stat-PO) = six-arm star-shaped NCO-poly(ethylene oxide-stat-propylene oxide), PGS = poly(glycerol sebacate), MOF = Metal-organic framework. References used in the Figure : Akentjew et al, [29] Jungst et al, [37] Hochleitner et al, [42] Zhang et al, [44] Gruber et al, [45] Skylar-Scott et al, [46] Lyons et al, [47] Apsite et al, [48] Li et al, [49] Wunner et al, [50] Mansi et al, [51] Bertlein et al, [52] Castilho et al, [53] Brown et al, [54] Federici et al, [55] Pien et al, [56] Van Genderen et al, [57] Mueller et al [58] have already been conducted in vivo, [32,35] showing the potential of the technique for synthetic small diameter vascular grafts for low patency with diameters and mechanics better mimicking the blood vessels compared to the conventional materials like PET and PTFE. Further, many studies have shown the beneficial surface characteristics of an SES fleece for the recreation of tubular constructs.…”