RESUMEN
Large skeletal muscle injuries, such as a volumetric muscle loss (VML), often result in an incomplete regeneration due to the formation of a non-contractile fibrotic scar tissue. This is, in part, due to the outbreak of an inflammatory response, which is not resolved over time, meaning that type-1 macrophages (M1, pro-inflammatory) involved in the initial stages of the process are not replaced by pro-regenerative type-2 macrophages (M2). Therefore, biomaterials that promote the shift from M1 to M2 are needed to achieve optimal regeneration in VML injuries. In this work, we used elastin-like recombinamers (ELRs) as biomaterials for the formation of non- (physical) and covalently (chemical) crosslinked bioactive and biodegradable hydrogels to fill the VML created in the tibialis anterior (TA) muscles of rats. These hydrogels promoted a higher infiltration of M2 within the site of injury in comparison to the non-treated control after 2 weeks (p<0.0001), indicating that the inflammatory response resolves faster in the presence of both types of ELR-based hydrogels. Moreover, there were not significant differences in the amount of collagen deposition between the samples treated with the chemical ELR hydrogel at 2 and 5 weeks, and this same result was found upon comparison of these samples with healthy tissue after 5 weeks, which implies that this treatment prevents fibrosis. The macrophage modulation also translated into the formation of myofibers that were morphologically more similar to those present in healthy muscle. Altogether, these results highlight that ELR hydrogels provide a friendly niche for infiltrating cells that biodegrades over time, leaving space to new muscle tissue. In addition, they orchestrate the shift of macrophage population toward M2, which resulted in the prevention of fibrosis in the case of the chemical hydrogel treatment and in a more healthy-like myofiber phenotype for both types of hydrogels. Further studies should focus in the assessment of the regeneration of skeletal muscle in larger animal models, where a more critical defect can be created and additional methods can be used to evaluate the functional recovery of skeletal muscle.
RESUMEN
UNLABELLED: To perform a historical introduction and a review of the mathematical model, emphasizing that our mathematical model may be the solution to the viscoelastic model. It is evident that the same experiment has been repeated over half a century, with similar results in all cases. We also show one of the projects we are working on: the electro-vesicogram for the evaluation of the filling phase, and Doppler uroflowmetry for the study of the voiding phase. METHODS: We have chosen and studied in depth the results Dr. Virseda presents in his thesis of one of the experiments performed in relation to the viscoelastic model. After applying analytical methods we reach a differential equation we suppose defines detrusor behaviour, as it has been explained by the viscoelastic model. The solution of this equation by means of the Laplace's transform enables to obtain the values of the incognitas set by urodynamics. Besides, we analyzed the behaviour of solutions' stability using a matricial method following the Lyapunov theory. The former may solve the incognitas for the voiding phase. We used urethral Doppler with simultaneous uroflowmetry to obtain the data equations demanded; this is what we named "Doppler uroflowmetry". The filling phase was studied by superficial electromiography. We named it "electrovesicogram". We attach images for both Doppler wave and electrovesicogram. They both are the projects we are working on. RESULTS: Currently we can only explain the methodology we are following. Indeed, this article is the first of a series in which we aim to explain the methodology we are following in detail: Doppler wave capture; mounting process photogram by photogram, and vectorization and cleaning of the wave, either Doppler or flow waves; treatment in autocad to obtain the vector; and management of the vector with the matalab software, which gives us the results we are looking for. CONCLUSIONS: It is intuitive to deduct the usefulness of these methods as not invasive techniques in the urodynamic diagnosis. We have our illusions in these projects which open a window to the future.