Human blood-derived extracellular vesicles in tendon tissue engineering and regenerative medicine applications

Tendon disorders, a major healthcare and socioeconomic burden worldwide, are often challenging to solve due to the tendons limited regenerative capacity. The main therapies currently used do not tackle the etiology of tendon injuries and therefore, there is an urgent need for alternative approaches that can effectively repair and regenerate tendons. Recently, extracellular vesicles (EVs) have gained increased attention due to their pivotal role in intercellular communication and ability to transfer bioactive molecules among cells, emerging as the next breakthrough in tissue engineering and regenerative medicine to promote endogenous tissue regeneration. This thesis focused on the development of different therapeutic strategies based on Human blood-derived EVs as biochemical cues to promote tendon tissue repair. Blood-derived EVs were obtained from platelets (Chapter IV) and monocyte-derived macrophages (Chapter V), and their morphology, size, and protein content were thoroughly assessed. Taking advantage of EVs bioactive content, their impact on human tendon-derived cells (hTDCs) behavior (Chapter VI) and inflammatory response (Chapter V) was investigated. Subsequently, a 3D bioengineered in vitro tendon model relying on hierarchically assembled yarns coated with collagen hydrogels encapsulating human adipose-derived stem cells (hASCs) was developed to shed light on the effect of EVs on stem cell tenogenic commitment (Chapter VII). Moreover, the regenerative potential of EVs was explored using a disease-like tendon model consisting of a nanofibrillar isotropic core coated with a platelet lysate hydrogel encapsulating human hTDCs (Chapter VIII). The work developed in this thesis provided evidence of the potential of blood-derived EVs in mediating tendon cells reparative processes, either alone or combined with biomaterials, by regulating stem cell differentiation, ECM remodeling, and immune response. Harnessing their features, EVs may have opened a new era for tendon tissue repair and regeneration approaches.

Name thesis:degree_name

Tese de doutoramento em Engenharia de Tecidos, Medicina Regenerativa e Células Estaminais

Grantor

Universidade do Minho

Year dc:date.issued

2023

Author dc:creator

• Graça, Ana Luísa Ferreira

Advisors dc:contributor.advisor

• Gomes, Manuela E.
• Gomez-Florit, Manuel

• Extracellular Vesicles
• Platelets
• Tendon
• Tissue Engineering
• Engenharia de Tecidos
• Plaquetas
• Tendão
• Vesiculas Extracelulares

Statement dc:rights

• openAccess

Licence dc:rights.uri

• http://creativecommons.org/licenses/by/4.0/

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1822/87950

OAI record oai:identifier

http://repositorium.sdum.uminho.pt/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Arepositorium.uminho.pt%3A1822%2F87950