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.

Common sugar alcohols used as artificial sweeteners and components of polymer networks represent low molecular weight polyhydroxymethylenes (PHMs) with the general formula [CH(OH)]nH2 but very low degree of polymerization (n = 2–6). Herein high molecular weight PHM (n >> 100) unparalleled in nature is tailored for 3D printing and medical applications by free radical polymerization of 1,3‐dioxol‐2‐one vinylene carbonate to produce polyvinylene carbonate (PVCA) which yields PHM by hydrolysis. Furthermore, PVCA is solution processable and enables PHM functionalization, membrane formation, and extrusion‐based 3D printing. Opposite to cellulose, amorphous PHM is plasticized by water and is readily functionalized via PVCA aminolysis/hydrolysis to produce polyhydroxymethylene urethane (PHMU), enable PHM crosslinking and coupling of PHM with amine‐functional components like gelatin. After hydrolysis/aminolysis the original PVCA shapes are retained. PVCA solution casting yields PVCA and PHM which exhibits uniform and hierarchic pore architectures. Asymmetric membranes, hydrogels, PHM/collagen blends, and electrospun nonwovens of PVCA, PHM, and PHMU are readily tailored for medical applications. 3D printing of PVCA dispersions containing hydroxyapatite affords porous PVCA, PHMU, and PHM scaffolds useful in regenerative medicine. PHM and functionalized PHMs as carbohydrate‐inspired multifunctional materials indicate in vitro biocompatibility and hold great promise for applications in medicine and health care.

In biomaterials research, biomechanics which support tissue regeneration steadily gains of importance. Hence, we have previously shown that gelatin‐based electrospun nonwoven mats (NWMs) with a distinct modulus of elasticity (3.2 kPa) promotes epithelial morphogenesis. Since molecular mechanisms of this morphogenesis are still unknown, the present study aims at identifying molecules, involved herein. Epithelia established on the NMWs showed persistence of the activated state of the epidermal growth factor receptor (EGF‐R), phosphorylated at the src‐specific tyrosine 845 (EGF‐RT845) throughout the observation period of 10 days. To elucidate whether the observed morphogenesis mechanistically involves EGF‐R signaling, we inhibited EGF‐R, by employing the EGF‐RT845 specific inhibitor Gefitinib (IRESSA®). Gefitinib administration yielded a reduced expression of the β1 integrin subunit, a well‐known cell–matrix interaction receptor, concomitant with downregulation of p42/44 ERK1/2 MAP‐kinase activity. To elucidate whether the observed downregulation of β1 is EGF‐RT845‐dependent or emerging from ERK1/2 signaling, we exposed epithelia, grown on the NWMs, with the ERK1/2‐directed inhibitor U0126. In the absence of Gefitinib, inhibition of p42/44 MAP‐kinase activity resulted in decreased β1 integrin protein levels, thus indicating that β1 expression is dependent on ERK1/2 and not EGF‐RT845. Our results showed the first time that an EGF‐R‐β1 integrin‐signaling axis, including ERK1/2, promotes NWM‐elasticity‐based epithelial morphogenesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 663–677, 2019.

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