Fabrication of Nanostructured Scaffolds …
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and degradable nature in vivo are combined and used for intended bone regeneration applications [45, 46]. The following polymer-ceramic composite showed
improved biomineralization with PLGA/HA nanofibers [47] and osteogenesis with
collagen/HA composite nanofibrous scaffold [48] for bone tissue engineering applications. Similarly, gelatin is also used instead of collagen, which is devoid of immunogenicity and disease transmission problems of the later, which present in most tissues,
including bone, tendon, ligament, and connective tissues [49]. While fabricating scaffold using gelatin and HA and electrospun nanofibers [50] showed improvement in
cell adhesion having integrin-binding sites and calcium ions from HA bound with
-COOH groups [51].
When it comes to bone tissue regeneration applications, the scaffold should mimic
the native bone structure, at the same time, should support the tissues mechanically
for cell attachment and differentiation and initial load-bearing with controlled degradation over the period. From a biological standpoint, the native bone structure of the
human is composed of organic (collagen polymer)/inorganic (hydroxyapatite crystals) composite [52]. Hence, the researcher should consider these aspects before
fabricating bone tissue engineering scaffold to mimic the nature bone architecture
better. In addition to that, the suitable blend of the different materials can modify the
mechanical properties and degradability of the scaffolds; thereby, composite biomaterials came into the picture for the development of biomimetic scaffolds [53]. Consequently, many researchers are attempted in this way and developed the bone tissue
engineering scaffolds with the combination of nHA and various natural (collagen,
gelatin, silk) and synthetic biodegradable polymers (PLA, PLGA, PCL [54–57] and
poly(propylene fumarate) (PPF)) [1]. However, HA possess poor sintering capabilities and inherent hardness, brittleness, and absence of flexibility lead to show
reduced mechanical properties, which limit its usage in weight-bearing applications.
A recent study showed that poor sintering of HA could overcome by developing into
nanostructured (nHA) materials [58], which can enhance the sinterability because of
higher surface free energy as a result of improvement in mechanical properties can be
achieved [59]. Currently, resorbable biomaterials used for bone-related applications
majorly include bi-phasic calcium phosphates such as HA and TCP, or their combination can be resorbed in the biological system over the period. Principally, HA is the
abundant inorganic mineral of Calcium phosphate (CaP) and present in the natural
bone tissues and teeth. Synthetic nHA and its closest chemical structure to the native
bone, which made them ideal candidate bone substitute used in various bone tissue
regeneration applications [60, 61].To take advantage of its excellent biocompatibility
and osteoconduction ability at the same time overcome the limitations of the HA,
can be combined with a different type of biodegradable polymers and fabricate as
bio-nanocomposite materials for bone defect repair applications [36, 62, 63].
Notably, to demonstrate the advantages of the nanostructured scaffolds, Shi
et al. developed the nano and micron-sized glass substrate, and the study results
concluded that the former nanostructured material showed greater MG63 cell attachment when compared to latter. This improved cellular response with nano-sized materials because of amorphous or lower crystalline nature and higher surface area for
cell adhesion and differentiation [64]. Likewise, another study reported by Heo et al.,
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