In large traumatic wounds and skin ulcers, an incompletely understood dysregulation of the inflammatory process often occurs, leading to the chronicization of the lesion. This phenomenon significantly reduces the quality of life and independence of affected individuals and poses a considerable healthcare challenge to achieve recovery, which is not always successful.
The main research focus of the "Regeneration, Molecular Oncology, and TGFß" group at IMIB aims to understand this phenomenon in order to develop solutions based on both cell therapy (CT) and the application of bioactive compounds (BC). We have demonstrated how CT, utilizing amniotic membrane (AM), can modulate TGFß signaling, which is involved in the stagnation of the lesion, thereby reactivating epithelialization. Detailed studies on the effects of AM on primary human keratinocytes and HaCaT cells, a stable keratinocyte line, have shown that this modulation triggers the expression of genes involved in proliferation and migration in the treated cells. These results may lead to changes in the cytoskeleton of epithelial cells, enhancing their capacity to interact with the extracellular matrix and leading to increased migratory performance observed in artificial wound assays, consistent with the properties observed in their clinical application in a compassionate use modality. Simultaneously, in strategies based on BC, notable work has been done in collaboration with members of the IMIDA Biotechnology Team on the abilities of Fibroin and Sericin peptides, derived from Bombyx Mori silk, to promote cell migration following direct in vitro exposure.
Despite this, the development of translational strategies based on both CT and BC faces significant technical limitations due to the nature and origin of these agents. Although AM is clinically effective, it needs to be obtained under controlled conditions and subjected to biosafety checks; its preservation requires cryogenic techniques, complicating storage and transport; additionally, it must be processed in a suitable environment, necessitating a clean room. In the case of peptides used as BC, the high proteolytic activity in the chronic wound bed hampers their in vivo efficacy. Therefore, to extend the use of these formidable therapeutic tools, it is essential to develop technical solutions to overcome these limitations.
Microstructured polymeric supports, known as "scaffolds," provide an ideal medium for the development of advanced bioengineering and cell therapy techniques. Currently, several material alternatives exist, among which electrospun Fibroin supports stand out due to their interesting properties in terms of biocompatibility, biodegradability, and mechanical strength. These supports, constructed in a three-dimensional matrix, allow for both cellular migration within them and nesting, making them useful in implantology. Moreover, various studies demonstrate their ability to be pre-functionalized with cells and/or peptides before application, emerging as a new generation of biomaterials with potential applications in regenerative medicine.
The implementation of technical solutions based on scaffolds functionalized with cells obtained from perinatal tissues, such as the amniotic membrane (AM), represents a scarcely explored field with the potential to address some of the aforementioned issues, particularly those related to the storage and transportation of AM derivatives. Additionally, the fact that the degradation products of these supports constitute a bioactive compound (BC) in themselves offers a formidable opportunity to evaluate the in vivo effects of Fibroin in a controlled and protected environment from proteolytic degradation. It is also noteworthy that both strategies, CT and BC, present synergistic potential when used in the same scaffold.
Given the increasing incidence of chronic ulcers, associated with the aging population, the development of thi