The degradation and the tissue response evoked by poly(1,3-trimethylene carbonate) [poly(TMC)] and copolymers of TMC with either 52 mol % D,L-lactide (DLLA) or 89 mol % epsilon-caprolactone (CL) were evaluated in vivo by subcutaneous implantation of polymer films in rats for periods up to one year. Poly(TMC) specimens were extensively degraded after 3 weeks and, as confirmed by histology, totally resorbed in less than a year. A fast linear decrease in thickness and mass without a change in molecular weight was observed. Initially an acute sterile inflammatory tissue reaction, caused by the implantation procedure, was observed, followed by a mild macrophage-mediated foreign body reaction that lasted during the resorption period of the polymer. It is concluded that in vivo, poly(TMC) is degraded via surface erosion involving cellular-mediated processes. The degradation of the copolymers was slower than that of poly(TMC), taking place via autocatalyzed bulk hydrolysis, preferentially of ester bonds. The TMC-DLLA copolymer degraded 20 times faster than the TMC-CL one. In both cases, the tissue reaction upon implantation resembled a sterile inflammatory reaction followed by a foreign body reaction that led to the polymer encapsulation. Significant mass loss was only observed for the TMC-DLLA copolymer, which underwent 96% mass loss in 1 year. When extensive mass loss started, a mild-to-moderate secondary foreign body reaction, related to clearance of the polymer fragments, was triggered. The results presented in this study demonstrate that poly(TMC) and both TMC copolymers are biodegradable and biocompatible materials, making these polymers attractive for the preparation of short- and long-term degradable devices for soft tissue engineering.
Neurodegenerative diseases generally result in irreversible neuronal damage and neuronal death. Cell therapy shows promise as a potential treatment for these diseases. However, the therapeutic targeted delivery of these cells and the in situ provision of a suitable microenvironment for their differentiation into functional neuronal networks remain challenging. A highly integrated multifunctional soft helical microswimmer featuring targeted neuronal cell delivery, on-demand localized wireless neuronal electrostimulation, and post-delivery enzymatic degradation is introduced. The helical soft body of the microswimmer is fabricated by two-photon lithography of the photocurable gelatin-methacryloyl (GelMA)-based hydrogel. The helical body is then impregnated with composite multiferroic nanoparticles displaying magnetoelectric features (MENPs). While the soft GelMA hydrogel chassis supports the cell growth, and is degraded by enzymes secreted by cells, the MENPs allow for the magnetic transportation of the bioactive chassis, and act as magnetically mediated electrostimulators of neuron-like cells. The unique combination of the materials makes these microswimmers highly integrated devices that fulfill several requirements for their future translation to clinical applications, such as cargo delivery, cell stimulation, and biodegradability. The authors envision that these devices will inspire new avenues for targeted cell therapies for traumatic injuries and diseases in the central nervous system.
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