Engineering Graded Tissue Interfaces - Structural Interfaces and Attachments in Biology - page 291

14.3 Regenerative Medicine Strategies to Engineer
Tissue Interfaces
Regeneration is defined as restoration of a tissue/organ to normal function following
an injury. Tissue engineering aims to create a biological substitute to replace or
repair tissue function by combining cells, scaffolds, and signaling molecules. In vivo
tissue engineering offers a tremendous advantage over traditional in vitro
approaches in that a functional tissue is fully integrated within the host physiology
by allowing cells to grow in an environment that physically and chemically repre-
sents the microenvironment of the damage and repair process. Engineering connec-
tive tissue interfaces is rather complex, as this requires combination of cells of
different phenotypes, scaffolds of different material types and physico-chemical
properties, and signals for different biological functions. The scaffolds aid in the
presentation of this information that includes a 3D template to form the tissue
structure, biological cues for cell adhesion, differentiation, and maturation. Differ-
ent approaches employed to regenerate tissue interfaces and fabricate biomimetic
scaffolds are briefly discussed in the following section.
14.3.1 Cells in Engineering Interfaces
The importance of cell-cell interactions for the formation of tissue interfaces have
been examined by coculturing cells relevant to the tissue types like fibroblasts,
osteoblasts and chondrocytes [ 22 , 23 ] in specific 3D microenvironments. A study
by Jiang et al. [ 24 ] looked into the effect of coculture of chondrocytes and
osteoblasts for osteochondral regeneration. Their results indicated that
chondrocytes and osteoblasts supported the formation of a mineralized tissue within
the proteoglycan-collagen-rich matrix. A promising approach is to promote tissue
synthesis, derived from single source progenitor cells that will be differentiated in
the construct to chondrocytes and osteoblasts. A recent study by Cheng et al . [ 25 ]
created a stem cell-derived osteochondral interface using an interface-specific
microenvironment in 3D configuration, via multilayered cocultures. Mesenchymal
stem cells (MSCs) were encapsulated in collagen microspheres and differentiated to
chondrogenic and osteogenic functional units. These pre-differentiated functional
microspheres were aggregated to form a trilayer scaffold with chondrogenic
microspheres on top, osteogenic microspheres at the bottom, and an intermediate
undifferentiated layer of MSCs in collagen microspheres. The study identified
chondrogenic medium as the optimal medium for the culture of the trilayered
constructs that generated a continuous calcified interface with hypertrophic
chondrocytes and type X collagen. Coculture of cell types relevant to the interface
might enhance the integration of different tissues at the interface, but the use of
progenitor cells from a single source and differentiating them to respective
phenotypes in response to biological cues is a more promising approach.