Research Themes in the Translational Medicine Living Lab
The research themes developed by the partners of the Translational Medicine Living Lab include several applications of advanced biomaterials mainly in the healthcare field. The regerative orthopaedics and neurology have been the focus of the research activities developed within the RINOVATIS project, aiming at solving pathologies related to the Central Nervous System (CNS) and the Perypheral Nervous System (PNS) as well as regenerating bone and cartilage tissues affected by Osteochondral (OC) defects.
Silver based antibacterial treatments
The image represents a collagen scaffold for cartilage regeneration.
Bone Tissue Scaffolds
The image representa a bi-layer scaffold, made of collagen (top layer) and HA (bottom layer).
Different types of scaffolds of different sizes, suitable for 30-mm gap:
• Tubular neural guides
• Longitudinally porous matrix
Controlled release devices
- , in collaboration with
- studied the best strategies to integrate capsules into different 3D scaffolds in order to realize the biological factors for the regeneration of both PNS and OC tissues. Development and optimization of the protocol for the synthesis of polyelectrolyte-based capsules, through the layer-by-layer (LbL) deposition technique, enabled the production of microcapsules composed by a cavity and a multilayer wall. Both compartments could be functionalized with bioactive molecules.
- Poli(lactic-co-glicolic) acid (PLGA) microspheres could also be synthetized, specifically by
- through the water/oil/water (w/o/w) double emulsion technique with subsequent evaporation of the organic solvent. This technique is ideal for loading PLGa with hydro-soluble molecules, such as proteins and other possible molecular regulators that could be gradually released in the target site, either through diffusion into the polymeric matrix composing the wall or exploiting the hydrolytic erosion of the matrix itself. The chitosan could also be employed to realize microsphere for the controlled release of growth factors.
- Rising the concentration of molecular regulators within the scaffolds through the immobilization of a large number of capsules, containing a high dose of regulators, on the outer and inner wall of the scaffold itself
- Allowing the load of different regulators within the scaffold through its functionalization with capsules containing such regulators
- Tuning the release of one or more regulators varying the capsule degradation kinetics
- Integrating polyelectrolyte within 3D porous scaffolds.
• Humid immobilization of microcapsules on type I collagen either pure or plasma modified samples
• Plasma processes at atmospheric pressure directly on the biological substrate (cells and culture medium).
The image represents the collagen CNS scaffolds.
The transcrittomic and bioinformatic analyses enable the investigation, conducted by Innovation Engineering Department (DII) of Università del Salento and Ospedale San Raffaele, about molecules able to promote and guide the regeneration of nervous and osteochondral tissues.
Although the laminin, fibronectin, vitronectin and fibrin create an initial substratefor regenerative processes, their persistence in the peripheral nerve provokes a delay in the regeration process, that ultimately lead to a progressive fiber loss and insufficient axonal regeneration. Potential novel molecules able to promote the regeneration, since they are involved in the organ neurogenesis and morphogenesis, have been studied as well as genes involved in the development of the nervous system have been identified. In particular, genes TMEM158 and EFBN1 appear specifically expressed by the Schwann cells, that compose the axon, and thus represent genes potentially involved in the PNS myelination during the regeneration/development phases.
The astroglial scar in the CNS represents an obstacle to the growth of the axonal stump which is proximal to the damage or rescission. BMP signaling is a biological process that activate astroglial scar formation, but it is possible to encapsulate BMP inhibitors in biodegradable PLGA microspheres.
Cartilage and bone matrix production is physiologically regulated by a group of growth factors that acts on their respective cell populations, chondrocytes and osteoblasts, stimulating specific pathways of synthetic activity, ultimately leading to the synthesis and release of matrix protein responsible for the tissue-specific biomechanic properties. IGF-1 plays a fundamental role in promoting cell proliferation and in inhibiting cell death during cartilage regeneration. BMP-2 promotes the recruitment of osteoprogenitor cells and regulates their differentiation towards the osteogenic line while TGFbeta-3 is essential for promoting chondrocyte differentiation.
Image represents a microvesicle sample.
Image represents nervous fibers crossectional slices obtained by means of electronic microscopy as selected, normalizeed and registered through novel visual inspection methodologies developed during the RINOVATIS project.
In vivo evaluation
Image represents the in vivo implant of a PNS scaffold in the sural nerve of a sheep.