Biomimetic Synthesis of Self-Assembled Mineralized Collagen-Based Composites for Bone Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 43

especially for large-size defects. Inadequate vascularization developed
in tissue-engineered materials has been a major obstacle for their clinical
applications. Because the amount of oxygen required for cell survival is
limited to a distance of approximately 200 m m from the supplying blood
vessel, long-term survival and function of constructed tissue substitutes
requires new blood vessels to provide nutrients and oxygen for the cells.
Therefore, an adequate blood vessel supplied to the newly formed tissue
and within the transplanted scaffold is thought to be essential in deter-
mining the success of new tissue regeneration. Promotion of angiogenesis
in tissue engineering is always one of the major topics of tissue regenera-
tion and tissue engineering. Vascular endothelial growth factor (VEGF)
and its analogues has been applied in bone tissue engineering. Localized
and sustained VEGF delivery improve mineralized tissue regeneration
but does not substantially enhance the presence of the osteoid matrix as
using a biomineral substrate alone does. This suggest that angiogenesis
speeds the differentiation and/or maturation of both infi ltrating osteo-
blasts and osteoblast precursor cells during neo-bone development,
perhaps by providing a conduit for delivery of osteo-inductive soluble
signals. It is noteworthy that the strategy to promote bone regeneration
via inducing angiogenesis could be particularly important in large-sized
defects, in which the presence of a vascular supply is perhaps more vital.
In both physiological and pathological processes, periosteum plays a
determinant role in bone formation and fracture healing, in addition to
the involvement of other important factors such as growth factors and
mechanical loading [102, 103]. The periosteum is a highly vascularized
tissue that contains osteogenic and chondrogenic progenitor cells as well
as other related bioactive factors. Transplantation of autogenous or allog-
enous periosteum has been applied successfully in the repair of various-
sized bone defects, especially in large bone defects. Bone healing induced
by periosteum has natural advantages over the other methods, such as
[16] healing with natural bone structure, optimal implant/host integrity,
appropriate vascularization and minimal ectopic ossifi cation through
encasing of the defect site. Zhang et al. pointed out that periosteum engi-
neering could assist in structural de novo bone formation and is therefore a
promising method for bone defect restoration [104].

2.4.3 Examples of Animal Models and Clinical Applications

Rabbits and rats on which are created artifi cial bone defects are used to
evaluate the in vivo performance of the nanocomposites. The results con-
fi rm that the composites have the excellent biocompatibility, osteocom-
patibility, and bioactivity with surrounding tissues, and the implants
stimulate the formation of new bone growth. Moreover, compared to
conventional biomaterials, the nanocomposites have been found to be