3D Printed Hierarchical Porous Poly(ε-caprolactone) Scaffolds from Pickering High Internal Phase Emulsion Templating.

In the realm of biomaterials, particularly bone tissue engineering, there has been a great increase in interest in scaffolds with hierarchical porosity and customizable multifunctionality. Recently, the three-dimensional (3D) printing of biopolymer-based inks (solutions or emulsions) has gained high popularity for fabricating tissue engineering scaffolds, which optimally satisfies the desired properties and performances. Herein, therefore, we explore the fabrication of 3D printed hierarchical porous scaffolds of poly(ε-caprolactone) (PCL) using the water-in-oil (w/o) Pickering PCL high internal phase emulsions (HIPEs) as the ink in 3D printer. The Pickering PCL HIPEs stabilized using hydrophobically modified nanoclay comprised of aqueous poly(vinyl alcohol) (PVA) as the dispersed phase. Rheological measurements suggested the shear thinning behavior of Pickering HIPEs having a dispersed droplet diameter of 3-25 µm. The pore morphology resembling the natural extracellular matrix and the mechanical properties of scaffolds were customized by tuning the emulsion composition and 3D printing parameters. In vitro biomineralization and drug release studies proved the scaffolds' potential in developing the apatite-rich bioactive interphase and controlled drug delivery, respectively. During in vitro osteoblast (MG63) growth experiments for up to 7 days, good adhesion and proliferation on PCL scaffolds confirmed their cytocompatibility, assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) analysis. This study suggests that the assembly of HIPE templates and 3D printing is a promising approach to creating hierarchical porous scaffolds potentially suitable for bone tissue engineering and can be stretched to other biopolymers as well.

Dual-functionalized Pickering HIPE templated poly(ɛ-caprolactone) scaffold for maxillofacial implants.

High internal phase emulsion (HIPE) templated poly (ɛ-caprolactone) (PCL) scaffolds have gained widespread attention for large-sized bone defects due to its tuneable 3D architecture and ease of fabricating crosslinked PCL (cPCL) scaffolds. However, extremely high stabilizer (surfactant or nanoparticle) concentration and negligence of microenvironment for regeneration sites like alveolar bones have restrained industrial acceptance of these scaffolds. Herein, we demonstrated the fabrication of nanocomposite cPCL scaffolds within Pickering HIPE templates stabilized using modified silica nanoparticles (mSiNP) concentrations as low as 0.1 to 1.0 wt%. Using an unconventional approach, the mSiNP Pickering stabilizer was added in dispersed phase, contradicting Bancroft's rule. The colloidal stability was attained due to faster drifting of mSiNP towards the interface when it was dispersed in silicone oil. Scaffolds with tuneable properties were fabricated by controlling the mSiNP concentration and ϕd. Further, cPCL scaffolds were functionalized using clove oil (CO) to improve their efficiency in eradicating S. aureus and E. coli by disrupting their cellular integrity. Additionally, formation of biofilm on the surface of the scaffolds was successfully inhibited by the incorporation of CO. CO-functionalized scaffolds demonstrated excellent cytocompatibility towards MG-63 cells allowing their successful adhesion and proliferation on the surface of the scaffolds.

Emulsion templated scaffolds of poly(ε-caprolactone) - a review.

The role of poly(ε-caprolactone) (PCL) and its 3D scaffolds in tissue engineering has already been established due to its ease of processing into long-term degradable implants and approval from the FDA. This review presents the role of high internal phase emulsion (HIPE) templating in the fabrication of PCL scaffolds, and the versatility of the technique along with challenges associated with it. Considering the huge potential of HIPE templating, which so far has mainly been focused on free radical polymerization of aqueous HIPEs, we provide a summary of how the technique has been expanded to non-aqueous HIPEs and other modes of polymerization such as ring-opening. The scope of coupling of HIPE templating with some of the advanced fabrication methods such as 3D printing or electrospinning is also explored.

Synthesis of Lactic Acid-Based Thermosetting Resins and Their Ageing and Biodegradability.

The present work is focused on the synthesis of bio-based thermoset polymers and their thermo-oxidative ageing and biodegradability. Toward this aim, bio-based thermoset resins with different chemical architectures were synthesized from lactic acid by direct condensation with ethylene glycol, glycerol and pentaerythritol. The resulting branched molecules with chain lengths (n) of three were then end-functionalized with methacrylic anhydride. The chemical structures of the synthesized lactic acid derivatives were confirmed by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FT-IR) before curing. To evaluate the effects of structure on their properties, the samples were investigated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and the tensile testing. The samples went through thermo-oxidative ageing and biodegradation; and their effects were investigated. FT-IR and 1H-NMR results showed that three different bio-based resins were synthesized using polycondensation and end-functionalization. Lactic acid derivatives showed great potential to be used as matrixes in polymer composites. The glass transition temperature of the cured resins ranged between 44 and 52 °C. Pentaerythritol/lactic acid cured resin had the highest tensile modulus and it was the most thermally stable among all three resins. Degradative processes during ageing of the samples lead to the changes in chemical structures and the variations in Young's modulus. Microscopic images showed the macro-scale surface degradation on a soil burial test.

Facile synthesis of templated macrocellular nanocomposite scaffold via emulsifier-free HIPE-ROP.

A macrocellular nanocomposite scaffold of crosslinked poly(ε-caprolactone) was made by conducting a ring-opening polymerization of an emulsifier-free Pickering high internal phase emulsion (HIPE). The Pickering HIPE formulation, stabilized using hydrophobically modified silica nanoparticles (mSiNPs), showed extraordinary stability up to a temperature of polymerization as high as 120 °C. The nanocomposite scaffolds demonstrated high porosity and a liquid uptake capacity of up to ∼23 g g-1. The scaffolds decorated with mSiNPs were mechanically robust and showed high resiliency under cyclic compression tests.

Hydrolytic Degradation of Porous Crosslinked Poly(ε-Caprolactone) Synthesized by High Internal Phase Emulsion Templating.

Porous poly(ε-caprolactone) (PCL) scaffolds were fabricated using the high internal polymerization emulsion (HIPE) technique. Bis(ε-caprolactone-4-yl) (BCY) was utilized as crosslinker. The crosslinking density and the volume fraction of the dispersed phase were varied in order to study the potential effect of these parameters on the hydrolytic degradation at 37 °C and 60 °C. After different hydrolysis times the remaining solid samples were analyzed by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), while the degradation products in the aqueous aging solutions were analyzed by laser desorption ionization-mass spectrometry (LDI-MS). The effect of temperature on the degradation process and release of degradation products was, as expected, significant. The temperature effect was also shown by FTIR analysis that displayed a pronounced increase in the intensity of the hydroxyl-group absorption band after 70 days of hydrolysis at 60 °C indicating significant cleavage of the polymer chains. LDI-MS analysis proved the release of oligomers ranging from dimers to hexamers. The product patterns were similar, but the relative m/z signal intensities increased with increasing time, temperature and crosslinking density, indicating larger amounts of released products. The latter is probably due to the decreasing degree of crystallinity as a function of amount of crosslinker. The porous structure and morphology of the scaffolds were lost during the aging. The higher the crosslinking density, the longer the scaffolds retained their original porous structure and morphology.

Electrospinning of a Near Gel Resin To Produce Cross-Linked Fibrous Matrices.

Electrospun fibers and matrices have been researched for their utility in various fields; however, because of poor mechanical strength and loss of structural integrity, their commercial viability is limited. A near gel resin (nGR) of polystyrene (PS) was used in the present approach to fabricate cross-linked fibrous matrices of better mechanical strength and oil adsorption while retaining the structural integrity. Electrospinnability of nGR was assessed in bulk (i.e., in styrene monomer) and solution (i.e., in dimethyl formamide) forms with variations in formulation and electrospinning conditions. Ultimately, a uniform cross-linked fibrous matrix of PS was prepared using an oil-in-water emulsion, where the oil phase composed of a monomer (styrene), an initiator (benzoyl peroxide), and a cross-linker (divinylbenzene) was dispersed in a continuous phase of aqueous poly(vinyl alcohol) (PVA). The monomer conversion in the oil phase was carried out below the gel point, and the nGR of PS formed in dispersed droplets was electrospun to fabricate uniform fibrous matrices with the help of a template polymer, that is, PVA. The effect of various material and process parameters on the gelation behavior, electrospinnability, and fiber uniformity was studied and optimized to produce uniform core-sheath fibrous matrices of cross-linked PS. Postelectrospinning heat treatment of matrices was carried out to achieve complete monomer conversion and cross-linking. Fiber formation behavior of the emulsion was assessed using ionic and nonionic surfactants. The cross-link density of the matrices was optimized to achieve the desired structural morphology and dimensional stability. The process of fabrication of emulsion electrospun cross-linked fibers can be further extended to a variety of other monomers in order to enhance the suitability of fibrous matrices for many applications.

Cellulose-Derived Nanographene Oxide Reinforced Macroporous Scaffolds of High Internal Phase Emulsion-Templated Cross-Linked Poly(ε-caprolactone).

Cellulose-derived nanographene oxide (nGO)-type carbon dot reinforced porous scaffolds of poly(ε-caprolactone) (PCL) were developed as templates from high internal phase emulsions (HIPE). The mechanical strength, structural integrity, and reusability of the scaffolds were enhanced via in situ cross-linking. An oil-in-oil (o/o) HIPE of ε-caprolactone monomer (CL) was made for this purpose, and the ring-opening polymerization of a continuous phase comprised of CL, catalyst (Sn(Oct)2), and cross-linker (bis(caprolactone-4-yl)) (BCY) was carried out. The functionalization of scaffolds with nGO was assessed along with its role as an effective Pickering stabilizer of the HIPEs. The pore size and porosity of the scaffolds were governed by HIPE morphology, which in turn was controlled by the amount of nGO and the volume fraction of the dispersed phase. The nGO-functionalized scaffolds of cross-linked PCL thus prepared were characterized for their morphological structure, mechanical strength, and oil sorption capacity. Enhanced oil adsorption of nGO-functionalized scaffolds proved them to be of higher potency compared to those made of neat PCL. Superior compressive strength and reusability of scaffolds for oil adsorption up to 40 times while maintaining the structural integrity for ≥25 sorption-desorption cycles added extra value to such scaffolds. The scaffolds also had excellent cell viability as evaluated by MG63 osteoblast-like cells and some bioactivity in the form of calcium phosphate mineralization on the surface of the scaffolds.