Page 375 - Advances in Biomechanics and Tissue Regeneration

372 18. CARTILAGE REGENERATION AND TISSUE ENGINEERING

As PB-MSCs can be obtained using a minimally invasive method and as their chondrogenic differentiation potential
seems to be comparable with or even higher than that of BM-MSCs, PB may be a promising source of cells for articular
cartilage regeneration.

18.4.1.2.6 SYNOVIUM
MSCs derived from synovial membranes (SM-MSCs) afford several advantages in terms of cartilage regeneration.
Such cells can be expanded in vitro for prolonged periods; their multilineage differentiation capability is not affected
by donor age or cell passage number. Such cells exhibit higher chondrogenic potential than BM-MSCs in vitro, and
thus, although the surface epitopes and proliferation potential are similar, cartilage pellets derived from synovium
were significantly larger than those derived from BM in patient-matched comparisons under optimal culture condi-
tions (pellet culture with TGF-β, dexamethasone, and BMP-2) [60, 87].
MSCs are present in the synovial fluid (SF-MSCs) of normal knee joints and increase in number after injury and as
osteoarthritis progresses [60, 88]; this is very useful when treating osteoarthritis patients. SF-MSCs share more MSC
antigens and genes with SM-MSCs than BM-MSCs. SF-MSCs recently exhibited chondrogenic potential in a rabbit
cartilage defect repair model; hyaline-like cartilage was detected macroscopically and histologically [60, 89].

18.4.2 Scaffolds
As previously mentioned, 2-D culture expansion of chondrocytes triggers dedifferentiation, but a 3-D environment
facilitates redifferentiation. To optimize chondrogenic characteristics, different 3-D approaches have been trialed (pel-
let culture, or the use of scaffolds to create structures that are physically and mechanically stable).
An optimal scaffold for cartilage tissue engineering should exhibit the following properties:

• Biocompatibility: The material must allow cells to proliferate and differentiate into chondrocytes with the
characteristic round morphology and create a microenvironment favoring the synthesis of a chondral matrix rich in
type II collagen and aggrecan. Also, immune reactions to the scaffold material must be minimized following in vivo
scaffold implantation [90].
• Porosity: Pores of appropriate size are essential for cell growth and flow transport of nutrients and metabolic
waste [91].
• Bioresorbability: Degradation and resorption must be controllable to match cell/tissue growth rates in vitro and/or
in vivo [57].
• Mechanical issues: The mechanical properties must be similar to those of native cartilage; this is crucial if neocartilage
is to be functional [92, 93].
A wide variety of materials are used to fabricate scaffolds; some of them are natural, and some others are synthetic.

18.4.2.1 Natural Materials
Natural materials are attractive because they are biochemically similar to cartilage and can be enzymatically
degraded. Both protein- and polysaccharide-based biomaterials are used. The first group features collagens, gelatin,
and fibrin, and the second group agarose, alginate, HA, and chitosan (CHT).

18.4.2.1.1 PROTEIN-BASED SCAFFOLDS
Collagen-based scaffolds may recreate environments that are rather physiological; collagen is the principal ECM
protein, allowing seeded cells to proliferate, differentiate, and generate cartilage-specific ECM [94].
The several collagen-based scaffolds include type I and II collagen hydrogels. Although the type I collagen used in
cartilage tissue engineering is of some utility in terms of cartilage defect repair, type II collagen more efficiently pro-
motes chondrogenic differentiation of embedded MSCs and supports a more homogeneous cell distribution through-
out the matrix [94, 95].
Studies combining both types of collagens have reported induction of chondrocyte-like morphologies and cartilage-
like matrices of seeded MSCs [96]. However, an important limitation is the poor mechanical properties of collagen-
based scaffolds. Therefore, collagens are often mixed with other biomaterials such as CHT, poly(L-lactic) acid
(PLLA), sodium alginate, and HA, perhaps mimicking the mechanical properties of native cartilage more accurately
[97, 98].
Type I/III or I/II collagen membranes are clinically used for matrix-induced autologous chondrocyte implantation
(MACI) [99, 100]. Although the membranes yielded promising results in terms of cartilage quality, their superiority com-
pared with ACI in the absence of membranes, or microfracture, requires corroboration in long-term follow-up studies.

II. MECHANOBIOLOGY AND TISSUE REGENERATION