Harnessing Cell–Biomaterial Interactions for Osteochondral Tissue Regeneration - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 80

6 Chondrogenesis in Biomaterials
6.1 Cell Homing
Biomaterials can be utilized as progenitor cell transplantation vehicles as well as to
provide moieties that can aid in cartilage regeneration. Tissue engineering strat-
egies may also involve leverage of biomaterials for the homing of progenitor cells,
such as MSCs, from the host to the construct to facilitate cartilage repair.
In general, the recruitment of endogenous host cells from a cell storage niche, such
as the bone marrow, to an anatomic compartment is considered cell homing [ 99 ].
MSC homing is also specifically defined as a MSC population that is arrested
within the vasculature of a tissue and transmigrated across the endothelium [ 100 ].
Natural healing and regeneration in defect tissues involves mobilization,
homing, and subsequent reparative actions at the injured sites [ 101 ]. MSCs
released from a cell storage niche first circulate in response to signals from distal
injured tissues (mobilization), and vasculature arrestment as well as transendo-
thelial migration (homing) occurs where MSCs will develop into mature healthy
tissue [ 100 , 101 ]. One of the early studies to investigate the origin and function of
the progenitor cells involved in the repair of full-thickness defects of articular
cartilage demonstrated that the repair was mediated entirely by proliferation and
chondrogenic differentiation of primitive MSCs from the bone marrow [ 102 ].
It was also indicated by autoradiography after labeling with 3 H-thymidine and
3 H-cytidine that the chondrocyte population from the residual adjacent articular
cartilage was not fully involved in defect repair. Therefore, this study emphasized
the importance of bone marrow as a progenitor cell reservoir for articular cartilage
regeneration and osteochondral tissue repair.
Owing to the potential drawbacks of clinical cell delivery, including undesired
immune responses, pathogen transmission, and technical barriers associated with
regulatory approval, cell homing to recruit MSCs from surrounding host tissues
has been suggested [ 99 ]. Nonetheless, there are a limited number of publications
investigating cell homing strategies for articular cartilage repair and chondrogenic
tissue regeneration [ 101 ]. Owing to the lack of vasculature in a cartilage tissue,
MSC homing strategies for cartilage tissue repair may need to target cell storage
sources such as bone marrow and synovial fluid. One recent study has shown the
potential use of synovium stem cells as a host cell source as well as the feasibility
of a biomaterial-based cell homing strategy to induce articular surface regenera-
tion [ 99 ]. The scaffold for the entire articular surface of the synovial joint was
anatomically customized with poly(e-caprolactone) (PCL) and 20% hydroxyapa-
tite powder based on the surface morphology of a rabbit forelimb joint.
An acellular scaffold containing interconnected microchannels (200-400 lmin
diameter) with and without TGF-b 3 infusion was implanted in a rabbit model.
TGF-b 3 was envisioned to serve as a cell homing molecule to accelerate functional
recovery and hyaline cartilage regeneration. Compared with the scaffolds in the
absence of TGF-b 3 , scaffolds infused with TGF-b 3 recruited a greater number of