Synthesis of Layered, Graded Bioscaffolds - Structural Interfaces and Attachments in Biology - page 348

undergoing clinical trials as an osteochondral regeneration template after successful
in vitro and preclinical trials demonstrated that these scaffolds can successfully
integrate into bone defects and show preliminary bony substitution and mineraliza-
tion as well as improved chondrogenesis in the CG compartment [ 61 , 62 ]. Addi-
tionally, the liquid-phase co-synthesis technique holds promise for the regeneration
of not only osteochondral defects, but also other physiological interfaces such as the
tendon-bone junction.
16.4 Core-Shell Composites for Orthopedic Tissue Engineering
Connective tissues such as tendon and ligaments transmit mechanical loads and
enable normal locomotion. These tissues are also commonly injured with over 17
million injuries occurring each year with annual costs in the tens of billions of
dollars in the United States alone [ 63 ]. The most serious injuries require surgical
intervention; such tendon and ligament injuries are responsible for hundreds of
thousands of surgical procedures each year in the United States [ 8 , 63 ].
One of the key challenges of orthopedic tissue engineering is to create scaffolds
that are bioactive and can support tissue regeneration while remaining mechanically
competent. The most common biomaterial designs for tendon and ligament tissue
engineering are electrospun or woven polymer mats [ 64 - 66 ]. While these constructs
can be designed with tensile moduli approaching the level of tendon, electrospun
mats are dense and essentially 2D materials with inadequate permeability, porosity,
and biodegradability. Highly porous scaffolds are alternative biomaterials that could
potentially supersede many of these drawbacks. Porous scaffolds have excellent
permeability and can be fabricated from natural, biodegradable materials. However,
these types of materials are typically orders of magnitude too weak for tendon
applications. To attempt to overcome this limitation, there are several common
methods of scaffold mechanical enhancement that do not have adverse effects on
construct bioactivity. For tendon and ligament scaffolds these include the creation of
aligned microstructure to mimic the native tissue architecture [ 65 , 67 ] and mechani-
cal stimulation of cell-seeded scaffold constructs [ 68 - 71 ]. While these methods can
marginally improve construct mechanical properties, they have not been successful
in reaching levels of native tendon.
While the multi-scale properties of tendon cannot be replicated by current
biomaterials technologies, composite materials have shown promise for complex
tissue engineering applications. Nature provides an alternative design scheme for
tendon tissue engineering applications: core-shell composites. Plant stems combine
a porous core with a dense shell to aid osmotic transport (core) while maintaining
sufficient tensile/bending stiffness (shell); many bird beaks also combine a dense
shell and porous core to enhance compressive strength and mechanical efficiency
[ 72 ]. This type of material has also been utilized to engineer high strength metal
tubing [ 73 ]. Mauck et al . have recently fabricated composites for intervertebral disk
tissue engineering consisting of an agarose gel mimicking the central nucleus