Articular Factors (FGF) and Insulin-like Growth Factor-1 (IGF-I).(5, 6,

Articular cartilage is a connective tissue
with low repair potential due to its avascular nature and lack of progenitor
cells.(1) Therefore, articular cartilage injuries present a challenging
problem for the musculoskeletal physicians. Many treatment option have been
developed during the last decades to repair damaged cartilage, such as
microfracture and mosaicplasty.(2) However, an adequate therapy for the long-term repair of cartilage
lesions and which recover totally the function of this tissue is still to be
developed. Tissue engineering and regenerative medicine (TERM) strategies hold
the promise to recover injury in cartilage to its native state by combining
cells, growth factors (GFs) and scaffolds with appropriate environmental
stimulation.(3, 4)

Despite the promising result reported by
chondrocyte implantation techniques, namely autologous chondrocyte implantation
(ACI) and matrix-induced autologous chondrocyte implantation (MACI), in a large
percentage of patients, they present many drawbacks such as the obtainable of
enough autologous chondrocytes during harvesting, loss of cellular
differentiation potential when cultured in vitro, and decreased capacity to
produce extracellular matrix (ECM).(2, 5)
Mesenchymal stem cells (MSCs) present advantages over chondrocytes, since they
can be obtained from an autologous source, in a less invasive procedure, and
present an higher proliferation capability together with their chondrogenic
differentiation potential.(6, 7)

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Bone marrow-derived MSCs (hBM-MSC) were
extensively studied in cartilage engineering and regeneration.(4, 8-13)
Conventionally, these MSCs are induced to differentiate into a certain lineage
by the supplementation of culture medium with defined exogenous bioactive
factors. The culture medium for the in vitro chondrogenesis of hBM-MSCs was
firstly described by Johnstone et al. in 1998.(14) The chondrogenic differentiation medium may contains different
combinations of the following bioactive factors: dexamethasone, ascorbic acid,
Transforming Growth Factor-? (TGF-?), Bone Morphogenetic Proteins (BMP),
Fibroblast Growth Factors (FGF) and Insulin-like Growth Factor-1 (IGF-I).(5, 6, 9, 15-21) Among
them, TGF-?3 and IGF-I have been the most effective and commonly used GFs, able
to induce the chondrogenic differentiation of hBM-MSCs, although the IGF-I has
been replaced by insulin-transferrin-selenious acid (ITS) or insulin.(9, 15, 16, 20, 22-24)
Therefore, we herein hypothesize that the availability of TGF- ?3 and IGF-I at
a biomaterial substrate would lead to a stable chondrogenic differentiation of
hBM-MSCs.

Autologous regeneration of tissues, where
both cells and bioactive factors are from the same patient, is an attractive
approach because it avoids the immune response.(25-27) Most
of the works in cartilage tissue engineering are based on mesenchymal stem
cells differentiated into the chondrogenic lineage by using recombinant GFs in
combination with biomaterials.(9, 17-20, 28) More
recently, platelet lysate (PL), consisting in a cocktail of different GFs
(e.g., bFGF, VEGF, TGF- ?, BMPs, PDGF-??, EGF, and IGF-I), provides an
autologous complex mixture of bioactive factors to the cells at the injury site.(27, 29)

The leading goal of this study is to
develop a biofunctionalized electrospun nanofiber mesh (NFM) with chondrogenic
induction capacity, through the immobilization of autologous TGF- ?3 and IGF-I
retrieved from platelet lysates. For that, we will take advantage of the
specific and efficient interactions between specific antibody and its antigen.

Based on this biological strategy, it will be possible to selectively bound the
GFs of interest (TGF-?3 and IGF-I) from a pool of highly concentrated GFs
present in PL. The chondrogenesis potential of electrospun NFMs with
immobilized TGF-?3 and IGF-I will be further assessed by culturing hBM-MSCs.

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