Cryo‐3D Printing of Hierarchically Porous Polyhydroxymethylene Scaffolds for Hard Tissue Regeneration

Abstract

High molecular weight polyhydroxymethylene (PHM) has a repeat unit identical to that of low molecular weight sugar alcohols and exhibits carbohydrate‐like properties. Herein, cryogenic extrusion‐based 3D printing is combined with a phase separation in water to fabricate hierarchically porous PHM scaffolds containing interconnected macro‐, micro‐, and nanopores. As PHM is infusible and insoluble in common solvents, its precursor polyvinylene carbonate (PVCA) dissolved in dimethylsulfoxide (DMSO) is used to 3D print hierarchically porous PVCA scaffolds that are converted into PHM by hydrolysis without impairing the pore architectures. Similar to low‐temperature deposition manufacturing, the PVCA/DMSO freezes on a build platform at −78 °C. However, instead of removing the frozen solvent by sublimation, the frozen scaffold is immersed in water to recover DMSO and to effect phase separation by precipitation. However, the computer‐guided printhead pathway controls macropore formation phase separation of frozen PVCA/DMSO upon contact with water accounts for simultaneous micro‐ and nanopore formation. Contrary to 3D printing of PVCA/DMSO at ambient temperature, this cryo‐3D printing process does not require shear thinning additives and affords significantly improved build precision with macropore sizes variable between 200 and 1500 µm. Cryo‐3D‐printed PHM scaffolds are biocompatible and promote osteoblast proliferation.

Biomimetic Polycaprolactone‐Graphene Oxide Composites for 3D Printing Bone Scaffolds

“…[5] Scaffolds play a central role in tissue engineering and serve as a temporary template to provide structural supports for guiding cells and constructing new tissue. [6,7] Ideally, the scaffold for such applications has to fulfill the following requirements, i) a 3D, porous structure with desirable surface chemistry to support cell growth, proliferation, and differentiation, [8,9] ii) open and interconnected pores for mass transport, [10] iii) a biocompatible and biodegradable substrate with tuned degradation rate with tissue ingrowth, [11] and iv) having mechanical features similar to the tissues at the site of implantation. [8] Polycaprolactone (PCL) is a synthetic, biocompatible, biodegradable, non-toxic, and simply obtainable aliphatic polyester that a U.S. Food and Drug Administration (FDA) certified as a safe biomaterial.…”

Recent Advances in Cryogenic 3D Printing Technologies

“…Reproduced with permission. [99] Copyright 2021, Wiley-VCH. [105] Copyright 2020, The Authors, published by Mary Ann Liebert.…”

“…Stolz et al cryo‐3D printed hierarchically porous polyhydroxymethylene (PHM) scaffolds for hard tissue regeneration. [ 99 ] The printing was carried out using the second‐generation 3D‐Bioplotter from EnvisionTEC. An aluminum substrate cooled with dry ice ( T = −78 °C) was used as the platform.…”

“…Figure 19. Fabrication of polyhydroxymethylene (PHM) scaffolds with hierarchic pore architectures by cryo-3D printing (left) of polyvinylene carbonate (PVCA) solutions in dimethylsulfoxide (DMSO) and subsequent conversion of PVCA to PHM by immersing PVCA scaffolds in aqueous NaOH (pH ¼ 12).Reproduced with permission [99]. Copyright 2021, Wiley-VCH.…”

Chemical upcycling of poly(bisphenol A carbonate) to vinylene carbonates through organocatalysis

“…24 Moreover, it can be used in radical polymerisation to form poly(vinylene carbonate), 25 a precursor of poly(hydroxymethylene, which has found applications in 3D printing. 26 In organic synthesis, it was historically used in Diels–Alder reactions 27 and it is now extensively used as a C1 or C2 synthon in annulation reactions promoted by C–H activation. 28 Functional vinylene carbonate derivatives have also gained a lot of interest.…”