Abstract:
1. Introduction:
With 2.2 million bone graft operations carried out annually worldwide, at an approximate cost
of $4.3 billion, bone is one of the most common body parts that needs repairing. Bone defects
are common due to tumor removal, trauma, or birth defects such as cleft palates. The majority
of bone graft operations use autograft, harvesting the patient’s own bone, usually from their
pelvis. However, the amount of bone is limited and the healing of the donor site tends to take
longer and be more painful than healing of the treatment site. Allogenic grafts are alternatives,
e.g. irradiated bone from cadavers (bone mineral from bone banks) and demineralized bone
matrix (bone mineral dissolved away using acids), but their mechanical properties are poor and
there is still risk of disease transmission and rejection. The bone tissue engineering approach
has provided an alternative method of bone regeneration, and 3-dimensional (3-D) printed
scaffolds have been extensively studied for the use in tissue engineering. Using this method, the
3-D scaffolds provide a template for seeded cells to stimulate cell proliferation and
differentiation, meanwhile providing an interconnected pore structure to allow nutrients to
penetrate into the scaffolds, resulting in the regeneration of bone defects.
Recently, there has been increasing interest in the use of bioactive glasses (BG) as scaffold
materials for bone repairing, due to their faster absorption rate compared to silicate glasses.
The structure and chemistry of BG can be tailored by changing their composition or their
thermal or environmental processing history. Jia et al. demonstrated that bioactive glass
scaffolds possessed exceptional mechanical properties and excellent osteogenic and angiogenic
properties, making them good candidates for large load-bearing applications. Compared with
non-mesoporous bioactive glass, mesoporous bioactive glass (MBG) has significantly better
effects on bone regeneration. The MBG scaffolds are similar to the porous structure of
subchondral bone, because of their highly inter-connected large pores (300–500 μm) and well-
ordered mesoporous structure (5 nm). Consequently, MBG scaffolds promote greatly-enhanced
attachment, spreading and proliferation of cells, resulting in high bioactivity and degradation
properties, due to the improved nano-pore volume and surface area. MBG is particularly
attractive due to its osteoconductive and drug delivery capabilities. Despite its advantages, MBG
suffers from poor mechanical strength, particularly under physiological load, limiting its
standalone application. Hence, hybridization with other biomaterial, such as biodegradable
polymers, graphene-based materials, and ceramic phases has been explored to overcome these
limitations. This review critically compares the latest strategies used to reinforce MBG scaffolds
and summarizes the effects of various fabrication techniques on their structural, mechanical,
and biological performance.
Material and Method:
2.1 Biomaterials Combined with MBG
3.1 Graphene Oxide (GO)
GO has been integrated with MBG to provide mechanical reinforcement and electrical
conductivity, enhancing osteogenesis and angiogenesis. MBG-GO scaffolds demonstrate
improved cell proliferation and in vivo bone formation [1].
3.2 Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)
PHBHHx, a biodegradable polyester, is compatible with 3D printing. MBG/PHBHHx scaffolds
show improved printability, strength, and cell proliferation, with excellent results in critical-sized
bone defects [2].
3.3 PLGA with Zeolitic Imidazolate Framework-8 (ZIF-8)
PLGA is a widely used polymer in bone scaffolds. When loaded with ZIF-8 and BMP-2, PLGA-
MBG scaffolds exhibit sustained release and enhanced osteoblast differentiation, indicating
superior bone healing potential [3].
3.4 Polyamide (PA)
MBG-coated PA scaffolds have open, interconnected pores and good mechanical properties. In
vivo results show effective osteogenesis and improved integration compared to PA alone [4].
3.5 β-Tricalcium Phosphate (β-TCP)
MBG-coated β-TCP scaffolds fabricated by 3D printing show increased mechanical stability and
bioactivity. The combination enhances hydroxyapatite formation and supports bone ingrowth
[5].
3.6 Cu–Mg Co-Doped MBG
Copper and magnesium ions enhance angiogenesis and antibacterial activity. Co-doped MBG
scaffolds support osteoblast adhesion, mineralization, and vascularization, addressing both
bone regeneration and infection risk [6].
3.7 Silk Fibroin
Natural silk protein combined with MBG improves scaffold flexibility and supports osteoblastic
differentiation, offering bioinspired solutions for bone regeneration [7].
3.8 Polycaprolactone (PCL)
PCL enhances the mechanical strength and flexibility of MBG composites. MBG-PCL scaffolds
exhibit osteoconductive behavior, with potential in load-bearing bone applications [8].
Comparative Analysis of Biomaterials
Table 1: Properties of Biomaterials Combined with MBG
Mechanical Drug
Biomaterial Key Benefits Bioactivity Challenges
Strength Delivery
Enhances
Graphene Aggregation,
osteogenesis, High High Moderate
Oxide (GO) toxicity concerns
conductivity
Biodegradable, Brittle in pure
PHBHHx Moderate Moderate Low
printable form
Drug release with Acidic degradation
PLGA + ZIF-8 Moderate High High
BMP-2 support by-products
Polyamide Durable, good
High Moderate Low Limited bioactivity
(PA) mechanical properties
Osteoconductive, Brittle, fast
β-TCP Moderate High Low
compatible with MBG resorption
Risk of
Cu-Mg Co- Angiogenic and
Moderate High Low cytotoxicity with
Doping antibacterial effects
high release
Biocompatible, natural Poor mechanical
Silk Fibroin Moderate High Low
ECM mimic integrity alone
Excellent flexibility Very slow
PCL High Moderate Low
and durability degradation rate
2.2 Fabrication Techniques for MBG-Based Scaffolds
2.2.1 Sol-Gel Synthesis
MBG is primarily synthesized through the sol-gel method using precursors like tetraethyl
orthosilicate (TEOS), calcium nitrate, and triethyl phosphate (TEP). The process involves
hydrolysis and condensation reactions in the presence of a structure-directing agent such as
Pluronic P123. The resulting gel is aged, dried, and calcined at 600–700°C to remove the
template and create a well-ordered mesoporous structure. Ion doping is introduced during the
precursor mixing step using salts such as Cu(NO₃)₂, Mg(NO₃)₂, or Zn(NO₃)₂.
2.2.2 Electrospinning
Electrospinning is used to produce nanofibrous MBG-polymer mats. MBG particles are
dispersed in a polymer solution (e.g., polyvinyl alcohol, PLGA, or gelatin) and subjected to high
voltage. The resulting fibers (diameter: 100–600 nm) mimic the extracellular matrix and offer
high surface area, supporting enhanced cell interactions.
2.2.3 3D Printing
MBG-based inks are formulated by blending MBG powder with biodegradable polymers such as
PCL or PLGA. Rheology is adjusted using biocompatible solvents or thickeners. Scaffolds are
printed layer-by-layer using extrusion-based 3D printers, with typical pore sizes ranging from
300–800 µm. This method enables precise customization of shape, architecture, and mechanical
performance, crucial for patient-specific bone defects.
2.2.4 Freeze-Drying
Commonly used for fabricating porous scaffolds. Offers high porosity and interconnectivity.
Figure 1. Schematic diagram of MBG composite scaffold fabrication techniques (to be inserted).
Technique Description Advantages Limitations Best Application
MBG synthesis MBG nanoparticle
Fine porosity, Brittle, time-
Sol-Gel through hydrolysis- and composite
chemical tunability consuming
condensation formation
Precision, Requires
Layer-by-layer
3D Printing customizable support Custom implants
structure fabrication
architecture materials
Nanofiber matrix
High surface area, Fragile Soft tissue scaffold
Electrospinning production via electric
ECM mimicry structure coating
fields
Simple, low- Poor Drug-loaded
Porous structures via
Freeze-drying temperature, high mechanical sponges, tissue
solvent sublimation
porosity strength templates
Discussion
The integration of MBG with complementary biomaterials results in advanced scaffolds with
enhanced properties. For instance, GO enhances osteoinductivity and electrical responsiveness,
which may favor nerve-related bone healing. Silk fibroin and PHBHHx provide biodegradable
support with moderate mechanical strength. Metal dopants such as copper and magnesium
significantly contribute to vascularization and antibacterial functions, key factors in clinical
healing.
Moreover, fabrication plays a critical role. 3D printing allows precise control over pore geometry,
while electrospinning provides a nanofibrous interface ideal for cell attachment. The sol-gel
method remains ideal for generating MBG particles and enabling ion doping but lacks the
macrostructural integrity needed for scaffolds. Hence, hybrid fabrication methods are emerging
to combine the best features.
6. Conclusion
MBG-based composite scaffolds represent a promising frontier in bone tissue engineering. By
integrating polymers, ions, and nanomaterials, researchers can tailor scaffold properties to
mimic natural bone more closely. With ongoing advances in fabrication techniques and
biological understanding, MBG composites are moving closer to clinical applications.
