Significant research effort has been directed toward the development of sustainable plastics that are high-performance, bioderived, and/or degrade into nontoxic byproducts in natural or engineered environments (i.e., industrial composting facilities). We report the low cytotoxicity of poly(γ-methyl-ε-caprolactone) (PMCL)-based materials and the hydrolysis product of PMCL, sodium 6-hydroxy-4-methylcaproate. The concentration of sodium 6-hydroxy-4-methylcaproate that leads to 50% cell death (TD 50 ) is 179 mM, a value that is similar to that of the hydrolysis product of polycaprolactone and higher than that of the hydrolysis product of polylactide. We also report the degradability of two PMCL materials with different architectures (cross-linked and linear triblock polymers) under simulated industrial composting conditions. These materials reached high degrees of carbon mineralization (>85%) over the course of 120 days as monitored by CO 2 evolution. Finally, we examined the industrial compostability of a new aromatic polyester, poly(salicylic methyl glycolide). This material reached 89% carbon mineralization after 120 days, an important finding given the recalcitrance toward degradation of ubiquitous aromatic polyesters.

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Biodegradable and implantable materials having elastomeric properties are highly desirable for many biomedical applications. Here, we report that poly­(lactide)-co-poly­(β-methyl-δ-valerolactone)-co-poly­(lactide) (PLA-PβMδVL-PLA), a thermoplastic triblock poly­(α-ester), has combined favorable properties of elasticity, biodegradability, and biocompatibility. This material exhibits excellent elastomeric properties in both dry and aqueous environments. The elongation at break is approximately 1000%, and stretched specimens completely recover to their original shape after force is removed. The material is degradable both in vitro and in vivo; it degrades more slowly than poly­(glycerol sebacate) and more rapidly than poly­(caprolactone) in vivo. Both the polymer and its degradation product show high cytocompatibility in vitro. The histopathological analysis of PLA-PβMδVL-PLA specimens implanted in the gluteal muscle of rats for 1, 4, and 8 weeks revealed similar tissue responses as compared with poly­(glycerol sebacate) and poly­(caprolactone) controls, two widely accepted implantable polymers, suggesting that PLA-PβMδVL-PLA can potentially be used as an implantable material with favorable in vivo biocompatibility. The thermoplastic nature allows this elastomer to be readily processed, as demonstrated by the facile fabrication of the substrates with topographical cues to enhance muscle cell alignment. These properties collectively make this polymer potentially highly valuable for applications such as medical devices and tissue engineering scaffolds.

Transdifferentiation of human non-muscle cells directly into myogenic cells by forced expression of MyoD represents one route to obtain highly desirable human myogenic cells. However, functional properties of the tissue constructs derived from these transdifferentiated cells have been rarely studied. Here, we report that three-dimensional (3D) tissue constructs engineered with iMyoD-hTERT-NHDFs, normal human dermal fibroblasts transduced with genes encoding human telomerase reverse transcriptase and doxycycline-inducible MyoD, generate detectable contractile forces in response to electrical stimuli upon MyoD expression. Withdrawal of doxycycline in the middle of 3D culture results in 3.05 and 2.28 times increases in twitch and tetanic forces, respectively, suggesting that temporally-controlled MyoD expression benefits functional myogenic differentiation of transdifferentiated myoblast-like cells. Treatment with CHIR99021, a Wnt activator, and DAPT, a Notch inhibitor, leads to further enhanced contractile forces. The ability of these abundant and potentially patient-specific and disease-specific cells to develop into functional skeletal muscle constructs makes them highly valuable for many applications, such as disease modeling.

Biodegradable and biocompatible elastomers are highly desirable for many biomedical applications. Here, we report synthesis and characterization of poly(ε-caprolactone)-co-poly(β-methyl-δ-valerolactone)-co-poly(ε-caprolactone) (PCL-PβMδVL-PCL) elastomers. These materials have strain to failure values greater than 1000%. Tensile set measurements according to an ASTM standard revealed a 98.24% strain recovery 10 min after the force was removed and complete strain recovery 40 min after the force was removed. The PβMδVL midblock is amorphous with a glass-transition temperature of −51 °C, and PCL end blocks are semicrystalline and have a melting temperature in the range of 52−55 °C. Due to their thermoplastic nature and the low melting temperature, these elastomers can be readily processed by printing, extrusion, or hot-pressing at 60 °C. Lysozyme, a model bioactive agent, was incorporated into a PCL-PβMδVL-PCL elastomer through melt blending in an extruder, and the blend was further hotpressed into films; both processing steps were performed at 60 °C. No loss of lysozyme bioactivity was observed. PCL-PβMδVL-PCL elastomers are as cytocompatible as tissue culture polystyrene in supporting cell viability and cell growth, and they are degradable in aqueous environments through hydrolysis. The degradable, cytocompatible, elastomeric, and thermoplastic properties of PCL-PβMδVL-PCL polymers collectively render them potentially valuable for many applications in the biomedical field, such as medical devices and tissue engineering scaffolds.