Page 321 - IJB-9-4

International Journal of Bioprinting 3D printing in bone regeneration and bone repair

1. Introduction manner, opening up new avenues for creating biomimetic
tissue . 3DP and 3D bioprinting also allow convenient
[17]
Bone is an anisotropic load-bearing tissue with the fine-tuning of scaffold designs through computer control,
potential to undergo self-healing after injury under normal enabling customization for individual patient needs .
[18]
circumstances. However, in a critical-sized defect (CSD)
that may be caused by trauma/accidents or the surgical 3DP allows complex scaffold compositions and structures
removal of cancerous tissue, delayed healing may lead to to be designed and fabricated through a layer-by-layer
[19]
[1]
permanent defects or a nonunion . Currently, bone grafting process . Some recent advances show that the hierarchical
techniques involving autografts, allografts, and xenografts porosity and biomimetic features of natural bone tissue can
are commonly used to treat bone CSDs . However, be replicated in BTE scaffolds using 3DP. For instance, a
[2]
these biological grafts have inherent limitations, such as scaffold comprising hydroxyapatite and tricalcium phosphate
limited donor tissue availability for autografts and disease (HA/TCP) has been fabricated through a slurry-based
transmission risks, mismatch, as well as immune response mask-image-projection-based stereolithography (MIP-SL)
[20]
[3]
after implantation for allografts and xenografts . An process to realize an intricate design of hierarchical pores .
ideal bone graft should also possess both high mechanical By tailoring scaffold fabrication using 3DP, the effects of
strength and bioactivity to provide structural support pore structure on the outcome of BTE can be thoroughly
to the defect area while actively inducing natural bone studied. For instance, a study has found that the mechanical
[4]
formation . The drawbacks of existing grafting methods properties or cell compatibility of polylactic acid (PLA)
and the complex requirements for bone regeneration in scaffolds were not affected by different pore sizes (50, 200,
[21]
CSDs have motivated researchers to develop strategies and 250 μm) . Interestingly, another study has shown that
for bone tissue engineering (BTE), which are commonly 3DP PLA scaffolds with 300, 600, and 900 μm pores were
considered to involve a combination of scaffolds, cells, found to have different effects on human articular cells, with
[5]
and growth factors to promote bone regeneration . BTE 600 μm pore scaffolds showing the highest cell adherence
[22]
scaffolds are expected to mimic the extracellular matrix and proliferation after 7 days . Four-dimensional printing
(ECM) of bone tissue while promoting oxygen diffusion, (4DP), which incorporates a temporal component into 3DP,
nutrient delivery, and waste removal. Additionally, the has also recently gained attention. 4DP utilizes the same
scaffold should be able to resist external forces to maintain technologies and methods as 3DP, but its scaffolds can alter
structural support within the defect and gradually degrade their form once in contact with environmental factors and
[6]
over time to make space for new bone formation . In order enable broader functionalities.
to facilitate bone ingrowth, BTE scaffolds should have a In recent years, a range of 3DP techniques have been
porosity greater than 90% and pore diameter between 300 applied in clinical practice for treating bone defects or
and 500 μm. The success of bone regeneration outcomes related conditions. Many reviews have predominantly
is largely determined by the functional capabilities of focused on specific areas of 3DP for bone regeneration. For
BTE scaffolds, thus justifying the significant emphasis of example, Wang et al. have reviewed the recent advances in
[7]
research on scaffold design and fabrication .
3DP for BTE and presented the philosophy and research
BTE scaffolds can be fabricated using conventional of fabrication and design in this field . Hassan et al. have
[23]
manufacturing techniques, such as solvent casting, gas analyzed the factors of bioresorbable/degradable templates
foaming, particulate leaching, freeze drying, and melt and their influence on BTE as well as the comparison of
molding [8-10] . However, these techniques rely on manual achieved BTE for different types of templated materials .
[24]
operation and often give rise to inconsistencies in fabrication Additionally, Bose et al. have reported recent advances
outcomes among studies due to difficulties in controlling the in 3DP using natural medical compounds (NMCs) with
pore size, geometry, interconnectivity, and spatial distribution powerful osteogenic potential and also highlighted the
as well as the material distribution and mechanical immense capacity of NMCs to integrate within BTE .
[25]
properties of scaffolds . Since their development and Interestingly, Wang et al. have focused on pharmaceutical
[11]
continual evolution over the last decade, 3DP techniques are electrospinning and 3DP for BTE, including the different
considered the most promising techniques for BTE scaffold types of materials, electrospun nanofibrous scaffolds,
manufacturing. The main categories of 3DP techniques and the diverse designs of 3DP scaffolds . Li et al. have
[26]
for BTE include fused filament fabrication (FFF), selective summarized the progress of mineralized collagen scaffolds
laser sintering (SLS), stereolithography (SLA) or digital (MCSs) for BTE. In their review, they proposed different
light processing (DLP), and direct ink writing (DIW) [12-16] . fabrication methods for MCSs, described the three aspects
In addition, recent developments in 3D bioprinting have of physical, chemical, and biological cues, as well as
allowed simultaneous incorporation of living cells together discussed the opportunities and challenges associated with
with growth factors into scaffolds in a spatially controlled MCSs for BTE . Bandyopadhyay et al. have illustrated the
[27]
Volume 9 Issue 4 (2023) 313 https://doi.org/10.18063/ijb.737