Human Platelet Lysates-based Scaffolds for Interfacial Multi-tissue Repair

Maxillofacial trauma, either caused by accidents or diseases, constitute a worldwide concern affecting millions of people. It represents a huge burden not only economically, but also on an individuals’ esthetical appearance and on everyday functions such eating and communicating, which can trigger severe physiological consequences, and society marginalization. Nevertheless, the complexity of recreating the native biosystem arrangement and interplay between a multitude of tissues, from bone to tendons, hampered the development of suitable regenerative strategies. Common scaffold solutions are limited by local inflammatory responses, suitable mechanical support and failure during implantation due to their weak and unstable properties.
InterLynk intends to develop a new regenerative strategy, i.e. a 3D printed structure composed of two or more biocompatible materials with light-responsive features. This structure, or scaffold, would be patient-specific and able to repair more than a type of tissue, namely, bone, tendon and/or cartilage.
To accomplish this idea, 5 Specific Objectives (SOs) were defined in this project. SO1 proposes the development of 3 printable biomaterial-based inks consisting of human platelet lysates as main matrix and combined with calcium phosphate ceramics and naringin therapeutic drug, respectively. SO2 consists on the upgrading of a 3D printer with photocuring and electrospray/writing heads so that multimaterial scaffolds can be successfully fabricated. SO3 involves a new computational toolbox for modulating the materials’ integration and manufacturing process. SO4 proposes the in vivo validation of the multimaterial printed scaffolds in a sheep model. SO5 envisages the creation of a user committee of stakeholders to implement strategies for overviewing and guiding the project decisions.

Biomaterial and protein-based inks became subject of high interest during the past few years among scientific community since their processing can generate personalized 3D structures that can be then translated to the market. In InterLynk project, human-based inks have been proposed to fabricate patient-specific and multimaterial scaffolds for interfacial tissue repair. So far, preliminary formulations of photocurable pristine platelet lysates have been achieved, including others combining calcium phosphate (CaP) particles and Naringin as osteoinductive compounds. Final formulations are still under investigation since preliminary formulations were investigated using a model protein, bovine serum albumin. In parallel, a photocurable fibre-layer made of synthetic polymers (PCL-LA) and produced by melt electrowriting has also been successfully developed and subsequently combined with CaP particles. In a strategy of having the best output from materials combination and print processing, a toolbox is being used for simulating such ends. Meanwhile, the printing system that will be used to assembly the multimaterial structure will be upgraded with a new photocuring head – already developed – and a melt-electrowriting head that is currently under development. This will allow the deposition of protein-based layers by extrusion printing interleaved with electrospun fibres. As a proof of concept, the regeneration of the interfacial tissues of temporomandibular joint was set as the target to be studied. Towards this goal, an Ethics Manual was built and dedicated working groups were implemented. Additionally, a Bio-Database is being created and regulatory aspects related to the project results are steadily being achieved.

The InterLynk consortium has been focused on the development of purely photocurable human-based biomaterial inks to fabricate patient-specific multimaterial scaffolds for the repair of interfacial tissues surrounding the temporomandibular joint. Pure photocurable platelet lysates biomaterial inks are currently being optimized in terms of printability and post-printability. This achievement will have a tremendous immunological and regenerative impact in therapies where foreign biomaterials are used at the target tissue. In parallel, composite inks composed of (I) photocurable platelet lysates containing calcium phosphate particles and (II) photocurable platelet lysates containing naringin are being investigated to potentially address more than a type of tissue. Photocurable electrowritten fibres, as predicted in the project, have been also fabricated to be used as inter-layers between the printed layers of platelet lysates based inks to maximize the surface area and prevent the delamination of the final multimaterial structure. Since the manufacture of multimaterial scaffolds can be highly challenging, a toolbox for simulating the behavior of materials and printing process is being used to predict the best strategy to combine and print the biomaterial formulations into multimaterial scaffolds with excellent biomechanical properties. Moreover, as the target tissue of InterLynk project is TMJ we already created an ethics manual and a bio-database that will allow to not only to study the bioperformance of the multimateiral scaffolds using an animal model but also to collect clinical data resulting from TMJ traumas and diseases to render and print patient-specific models. With this in mind, InterLynk holds an immense potential of achieving a proper prototype, capable of repairing TMJ interfacial tissues and consequently have a significant impact in patients recovery time. This represents not only a huge economic impact by reducing related healthcare costs, but also an enormous community impact by improving peoples’ quality of life and societal integration.

Periodic Reporting for period 1 - InterLynk (Human Platelet Lysates-based Scaffolds for Interfacial Multi-tissue Repair)

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