Application of Chitosan-Based Biomaterials in Tissue Engineering - Chitosan Based Hydrogels: Functions and Applications - page 438

one of the active growth factors regulating mitosis of chondrocytes and accelerates the syn-
thesis of collagen, fibronectin, and proteoglycan in articular cartilage [153]. Therefore, a
combination of the use of growth factors and a porous scaffold might substantially improve
the cartilage-forming efficacy. A porous freeze-dried chitosan-based scaffold incorporating
TGF-β1-loaded microspheres was used for the treatment of cartilage defects. Lee et al. [154]
found that porous chitosan-collagen-GAG scaffolds loaded with TGF-β1 exhibited con-
trolled release of TGF-β1 and promoted cartilage regeneration. Moreover, the proliferation
capacity of chitosan-based scaffold loaded with TGF-β1 is much higher than that without
TGF-β1. Long-term use of TGF-β1 can bring side effects, such as destroying the cartilage and
partial ossification in vivo , and disturbance of proteoglycan homeostasis. TGF-β1 incorpo-
rated into the chitosan-based porous scaffold showed a burst release at the initial stage; this
release kinetics is advantageous in the promotion of cartilage regeneration when the body
needs high protein concentration in the initial stage and avoids the side effects of long-term
use. In addition, other growth factors, such as FGFs, PDGFs, EGFs, and so on, play an impor-
tant role in the proliferation of chondrocytes and production of ECM. Recently, tissue engi-
neering and local therapeutic gene delivery systems have been paid much attention in the
cartilage natural healing process. Guo et al. [155] designed a gene-activated matrix consist-
ing of plasmid DNA and biodegradable chitosan-gelatin as scaffolds for cartilage regenera-
tion. The plasmid DNA in the scaffolds can be partly protected from degradation by human
serum and transfected to the primary chondrocytes. The combination of chitosan-based
cartilage scaffolds with gene therapy and the use of growth factors will hopefully improve
the long-term outcomes of cartilage repair in clinical settings.
9.5.4 bone
Bone is a dynamic and highly vascularized tissue that continuously rebuilds its structure.
Bone tissue has a hierarchical organization over length scales that span several orders of
magnitude from the macro-(centimeter) scale to the nanostructured (ECM or ECM) com-
ponents ( cf. Figure 9.30) [156]. It is actually an inorganic-organic composite mainly made
up of nano-HAp (nHAp) (Ca 10 (PO 4 ) 6 (OH) 2 ; and collagen fibers. The nanocomposite struc-
ture is integral to the requisite compressive strength and high fracture toughness of bone.
Bone tissue itself is arranged either in a compact pattern (cortical bone) or in a trabecular
pattern (cancellous bone). Every year, millions of patients, particularly among the aged, are
suffering from bone defects arising from trauma, tumor, or bone diseases and of course
several are dying due to insufficient ideal bone substitute. Bone defects represent a chal-
lenge for orthopedic and reconstructive surgeons. Surgical treatments of large bone defects
include the Ilizarov method, or bone transport, and bone graft transplant. Currently, the
gold standard treatment is the use of a procedure called autografting. The traditional
biological methods of bone-defect management include autografting and allografting
bone. Since bone grafts are avascular and dependent on diffusion, the size of the defect
and the viability of the host bed can limit their application. Nevertheless, its use is severely
hampered by its short supply and the considerable donor site morbidity associated with
the harvest [157]. Bone tissue engineering techniques based on autogenous cell-tissue
transplantation would eliminate these problems. In this regard, 3D scaffolds, osteoblasts
or cells that can become osteoblasts, and regulating factors that promote cell recruitment,
growth, differentiation, are very important factors to improve the formation of new bone
( cf. Figure 9.31) [139].
Bone tissue undergoes constant remodeling in order to ensure that its structural
integrity is maintained. The formation of new bone is a complicated process that involves