Cell Therapy for the Enhancement of Bone Repair - Engineered Bone: Tissue Engineering Intelligence Unit - page 157

easiest source of cells. Few reports, starting from the historical data by Luria and coworkers, 61
suggest that it is possible to isolate from peripheral blood a population of fibroblasts. 40,62 These
peripheral blood fibrocytes would be in principle the population of cells reaching sites of tissue
injury and contributing to connective scar tissue formation. They display a distinct cell surface
phenotype (CD34-/CD45-/collagen I+/b1 integrin subunit), and are an abundant source of
cytokines and growth factors that function to attract and activate inflammatory and connective
tissue cells. 40
In conclusion, cells potentially interesting for bone tissue engineering can be isolated from
a variety of tissues. Still, the only cell system widely studied and used for both preclinical and
clinical applications remains the one originally described by Friedenstein and will be therefore
discussed in the following sections. 39 It would be intriguing to speculate that, given proper
selection of subpopulations and specific culture conditions, either any tissue contains a totipo-
tent stem cell compartment or committed cells can be induced to “dedifferentiate” up to the
level of stem cell.
Scaffolds and the Design of the Delivery Vehicle
Scaffolds are the key factors required to start and direct the cascade of cellular events leading
to bone repair. Delivering osteoprogenitor cells within a suitable tridimensional matrix is thus
of critical importance for engineering bone tissue. Scaffolds in bone tissue engineering have to
be considered as a crucial component of the experimental design; the scaffold is the element
mimicking the extracellular matrix in a regenerating bone microenvironment. This concept
implies that the scaffold is not only a simple inert delivery vehicle, but it has to be “informa-
tive” to the cells
The primary role of biomaterials in orthopaedic applications rests upon their osteoconductive
properties coupled to the ability to integrate effectively with bone tissue. 63-69 Thus a proper
biomaterial is supposed to easily integrate with the surrounding tissue and to allow new bone
tissue ingrowth. But biomaterials have also to serve as delivery vehicle of cells and signaling
molecules. 70,71 Their architecture has to be permissive for blood vessels to colonize even larger
structures. Finally they should be biocompatible and resorbable. From this point of view, the
new generation of bioceramics are indeed a undoubted candidate. 72,73 Bioceramics in fact mimics
a preexisting bone surface and bone cells deposit new bone matrix on the ceramics surface. 66,74
Porous bioceramics (hydroxyapatite (HA), and tricalcium phosphate (TCP)) are osteoconductive,
have a favorable bone affinity, 66,69,75-79 and are free from risks of rejection or infection. 66,67,75,78,80
Synthetic bioceramics are readily available, and can be used to custom design implants suited
to individual applications. However, they do not represent per se a mechanically sound mate-
rial, 79,81-83 and the performance of a theoretical ceramic implants depends on the local me-
chanical demands of the injuried bone, and on the efficient deposition and integration of new
bone into the implant.
An important improvement in this field is represented by synthetic porous scaffolds (Fig.
3). In this case in fact the internal architecture can be intelligently designed and the density and
the biomechanical properties of the material can be predetermined. The result is that the sur-
face available for tissue regeneration as well as for cell delivery can be extremely high. The
increase in surface can also have positive effects on scaffold resorbability. The alternative ap-
proach to synthetic ceramics is to use natural scaffolds which have an intrinsic structure highly
compatible with tissue ingrowth. One such scaffolds is the coral exoskeleton which present a
completely interconnected porous structure and good biomechanical and architectural proper-
ties. 84-87
Because of their osteoconductive properties and their ability to “integrate” with bone tissue,
HA and TCP bioceramics are perhaps the biomaterials most widely studied and used. The
osteoconductivity and the ability to be invaded by blood vessels of porous bioceramics can be
improved by manipulating the structural characteristics of the finished implant device.
As outlined already, bone tissue engineering strategies attempt to provide the injured seg-
ment with scaffolds of initially poor mechanical properties, highly permissive to new bone