Chien Yi Wee

In the field of bone tissue engineering, silicon (Si) has been found as an essential element for bone growth. However, the use of silicon in bioceramics microspheres remains limited. In this work, different weight percentages (0.8, 1.6, and 2.4 wt %) of silicon was incorporated into hydroxyapatite and fabricated into microspheres. 2.4 wt % of Si incorporated into HAp microspheres (2.4 SiHAp) were found to enhance functional properties of the microspheres which resulted in improved cell viability of human mesenchymal stem cells (hMSCs), demonstrating rapid cell proliferation rates resulting in high cell density accumulated on the surface of the microspheres which in turn permitted better hMSCs differentiation into osteoblasts when validated by bone marker assays (Type I collagen, alkaline phosphatase, osteocalcin, and osteopontin) compared to apatite microspheres of lower wt % of Si incorporated and non‐substituted HAp (2.4 SiHAp >1.6 SiHAp >0.8 SiHAp > HAp). SEM images displayed the densest cell population on 2.4 SiHAp surfaces with the greatest degree of cell stretching and bridging between neighboring microspheres. Incorporation of silicon into apatite microspheres was found to accelerate the rate and number of apatite nucleation sites formed when subjected to physiological conditions improving the interface between the microsphere scaffolds and bone forming cells, facilitating better adhesion and proliferation.

Drop on demand (DOD) inkjet method is a cost‐efficient way of producing hydroxyapatite (HAp) microsphere scaffolds with narrow size distribution. However, DOD fabrication parameters may influence the yield and characteristics of the microsphere scaffolds. Testing different permutations and combinations of fabrication parameters is costly and time consuming. Taguchi method could be used as a predictive tool for optimizing the key fabrication parameters to produce HAp microspheres with desired yield and properties, minimizing the number of experimental combinations to be tested. The aim of this study is to investigate the influence of the fabrication parameters on the characteristics of the microspheres formed and determine optimum parameter conditions for producing high yield HAp microsphere scaffolds with the desired properties intended to serve as potential bone substitutes. We aimed to achieve microspheres with high production yield, microsphere size of 2 concentration. Based on signal‐to‐noise (S/N) ratio analysis, the identified optimum parameter conditions for operating pressure, shutter speed duration, nozzle height and CaCl₂ concentration to be 0.9–1.3 bar, 100 ms, 8 cm and 0.4 M respectively. The microspheres obtained had an average size of 213 μm, 0.45 μm micropore size, high sphericity index of 0.95 and high production yield of 98%. Confirmation tests and ANOVA results affirms the validity of Taguchi method in optimizing HAp microspheres with high yield, desired size, micropore size and shape. HAp microsphere scaffolds produced by optimum conditions were subjected to a 7‐day in‐vitro study. Cells remained viable and continued to proliferate (increased 1.2‐fold) over 7 days with microspheres maintaining high cell density with cells bridging between microspheres. Alkaline phosphatase (ALP) assay increased 1.5‐fold from day 1, suggesting good osteogenic potency of HAp microspheres as potential bone substitutes.

Bone regeneration is a dynamic and complex process that encompasses active recruitment of osteogenic cells, proliferation and differentiation of such cells, formation of bone matrix and bone remodelling. In recent years, microspheres have garnered much attention due to their capability to serve as tissue engineering scaffolds and vehicles for drug delivery for trauma therapy. This review will present the use and evolution of microspheres over years of research in the field of bone regenerative medicine. Different types of microspheres such as polymeric, bioceramics and composite-based will be evaluated on how they play a role in aiding bone regeneration. Furthermore, the advantages and disadvantages of the applications of the types microspheres in bone engineering will be highlighted. This review will also include common fabrication methodologies utilised to produce such microspheres. Lastly, a brief perspective on the future direction of microspheres research for bone engineering will be discussed.