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.

The aim of this study was to evaluate injectable, in situ cross-linkable elastin-like recombinamers (ELRs) for osteochondral repair. Both the ELR-based hydrogel alone and the ELR-based hydrogel embedded with rabbit mesenchymal stromal cells (rMSCs) were tested for the regeneration of critical subchondral defects in 10 New Zealand rabbits. Thus, cylindrical osteochondral defects were filled with an aqueous solution of ELRs and the animals sacrificed at 4 months for histological and gross evaluation of features of biomaterial performance, including integration, cellular infiltration, surrounding matrix quality and the new matrix in the defects. Although both approaches helped cartilage regeneration, the results suggest that the specific composition of the rMSC-containing hydrogel permitted adequate bone regeneration, whereas the ELR-based hydrogel alone led to an excellent regeneration of hyaline cartilage. In conclusion, the ELR cross-linker solution can be easily delivered and forms a stable well-integrated hydrogel that supports infiltration and de novo matrix synthesis.

Topical administration of T1225 oil-based azithromycin eyedrops was well tolerated in both unmanipulated hen corneas and those treated with corneal refractive surgery (PRK and LASIK). T1225 demonstrated a potent antibiotic effect after LASIK treatment.

No abstract

Oclusión vascular y daño histológico 82 Sangre completa 64.1 (57.5-69.9) ml/kg Frecuencia respiratoria 85.5 (66-114)/min Volumen tidal 0.86 (0.60-1.25) ml Volumen minuto 0.073 (0.05-0.101) ml Volumen de eyección 1.3-2.0 ml/latido. Tabla 7: Parámetros cardiorespiratorios de la rata, modificado de (130, 131, 133-135) Peso adulto: Macho 300-400 gr. Hembra 250-300 gr. Esperanza de vida: Usual 2.5-3 años Máxima 4 años y 8 meses Área superficie 0.03-0.06 cm2 Número de cromosomas 42 Consumo de agua 80-110 ml/kg/dia Consumo de comida 100 gr/kg/dia