RESUMEN
The increase in fracture rates and/or problems associated with missing bones due to accidents or various pathologies generates socio-health problems with a very high impact. Tissue engineering aims to offer some kind of strategy to promote the repair of damaged tissue or its restoration as close as possible to the original tissue. Among the alternatives proposed by this specialty, the development of scaffolds obtained from recombinant proteins is of special importance. Furthermore, science and technology have advanced to obtain recombinant chimera's proteins. This review aims to offer a synthetic description of the latest and most outstanding advances made with these types of scaffolds, particularly emphasizing the main recombinant proteins that can be used to construct scaffolds in their own right, i.e., not only to impregnate them, but also to make scaffolds from their complex structure, with the purpose of being considered in bone regenerative medicine in the near future.
Asunto(s)
Huesos/metabolismo , Osteogénesis , Proteínas Recombinantes de Fusión , Medicina Regenerativa , Ingeniería de Tejidos , Andamios del Tejido/química , Humanos , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismoRESUMEN
The morbidity of bone fractures and defects is steadily increasing due to changes in the age pyramid. As such, novel biomaterials that are able to promote the healing and regeneration of injured bones are needed to overcome the limitations of auto-, allo-, and xenografts, while providing a ready-to-use product that may help to minimize surgical invasiveness and duration. In this regard, recombinant biomaterials, such as elastin-like recombinamers (ELRs), are very promising as their design can be tailored by genetic engineering, thus allowing scalable production and batch-to-batch consistency, among others. Furthermore, they can self-assemble into physically crosslinked hydrogels above a certain transition temperature, in this case body temperature, but are injectable below this temperature, thereby markedly reducing surgical invasiveness. In this study, we have developed two bioactive hydrogel-forming ELRs, one including the osteogenic and osteoinductive bone morphogenetic protein-2 (BMP-2) and the other the Arg-Gly-Asp (RGD) cell adhesion motif. The combination of these two novel ELRs results in a BMP-2-loaded extracellular matrix-like hydrogel. Moreover, elastase-sensitive domains were included in both ELR molecules, thereby conferring biodegradation as a result of enzymatic cleavage and avoiding the need for scaffold removal after bone regeneration. Both ELRs and their combination showed excellent cytocompatibility, and the culture of cells on RGD-containing ELRs resulted in optimal cell adhesion. In addition, hydrogels based on a mixture of both ELRs were implanted in a pilot study involving a femoral bone injury model in New Zealand white rabbits, showing complete regeneration in six out of seven cases, with the other showing partial closure of the defect. Moreover, bone neoformation was confirmed using different techniques, such as radiography, computed tomography, and histology. This hydrogel system therefore displays significant potential in the regeneration of bone defects, promoting self-regeneration by the surrounding tissue with no involvement of stem cells or osteogenic factors other than BMP-2, which is released in a controlled manner by elastase-mediated cleavage from the ELR backbone.