Methods of producing three dimensional electrospun scaffolds for bone tissue engineering: A review.

Bone is a dynamic, living tissue that exists and renews itself continuously in a 3D manner. Nevertheless, complex clinical conditions require a bone substitute to replace the defective bone and/or accelerate bone healing. Bone tissue engineering aims to treat bone defects that fail to heal on their own. Electrospinning provides an opportunity to create nano- to micro-fibrous scaffolds that mimic the architecture of the natural extracellular matrix (ECM) with high porosity and large specific surface area. Despite these advantages, traditional electrospun meshes can only provide a 2D architecture for cell attachment and proliferation rather than the 3D attachment in native tissue. Fabrication of 3D electrospun scaffolds for bone tissue regeneration is a challenging task, which has attracted significant attention over the past couple of decades. This review highlights recent strategies used to produce 3D electrospun/co-electrospun scaffolds for bone tissue applications describing the materials and procedures. It also considers combining conventional and coaxial electrospinning with other scaffold manufacturing techniques to produce 3D structures which have the potential to engineer missing bone in the human body.Graphical abstract[Formula: see text].

Optimising micro-hydroxyapatite reinforced poly(lactide acid) electrospun scaffolds for bone tissue engineering.

HA-mineralised composite electrospun scaffolds have been introduced for bone regeneration due to their ability to mimic both morphological features and chemical composition of natural bone ECM. Micro-sized HA is generally avoided in electrospinning due to its reduced bioactivity compared to nano-sized HA due to the lower surface area. However, the high surface area of nanoparticles provides a very high surface energy, leading to agglomeration. Thus, the probability of nanoparticles clumping leading to premature mechanical failure is higher than for microparticles at higher filler content. In this study, two micron-sized hydroxyapatites were investigated for electrospinning with PLA at various contents, namely spray dried HA (HA1) and sintered HA (HA2) particles to examine the effect of polymer concentration, filler type and filler concentration on the morphology of the scaffolds, in addition to the mechanical properties and bioactivity. SEM results showed that fibre diameter and surface roughness of 15 and 20 wt% PLA fibres were significantly affected by incorporation of either HA. The apatite precipitation rates for HA1 and HA2-filled scaffolds immersed in simulated body fluid (SBF) were similar, however, it was affected by the fibre diameter and the presence of HA particles on the fibre surface. Degradation rates of HA2-filled scaffolds in vitro over 14 days was lower than for HA1-filled scaffolds due to enhanced dispersion of HA2 within PLA matrix and reduced cavities in PLA/HA2 interface. Finally, increasing filler surface area led to enhanced thermal stability as it reduced thermal degradation of the polymer.

Hybrid core-shell scaffolds for bone tissue engineering.

The tissue engineering applications of coaxial electrospinning are growing due to the potential increased functionality of the fibres compared to basic electrospinning. Previous studies of core and shell scaffolds have placed the active elements in the core, however, the surface response to a biomaterial affects the subsequent behaviour, thus here hydroxyapatite (HA) was added to the shell. Coaxial electrospun polycaprolactone (PCL)-polylactic acid (PLA)/HA (core-shell) scaffolds were produced in 2D sheets using a plate collector, or 3D tubes for bone tissue engineering using a rotating needle collector. The scaffolds include high hydroxyapatite content while retaining their structural and mechanical integrity. The effect of the collector type on fibre diameter, fibre alignment and mechanical properties have been evaluated, and the impact of HA incorporation on bioactivity, BMP-2 release, cell behaviour and mechanical properties for up to 12 weeks degradation were assessed. Fibre uniformity in coaxial electrospinning depends on the relative flow rate of the core and shell solutions. Using a rotating needle collector increased fibre alignment compared to a stationary collector, without affecting fibre diameter significantly, while HA content increased fibre non-uniformity. Coaxial PCL-PLA/HA fibres exhibited significantly higher bioactivity compared to PCL-PLA scaffolds due to the surface exposure of the HA particles. Apatite formation increased with increasing SBF immersion time. Coaxial tubular scaffolds with and without HA incorporation showed gradual reductions in their mechanical properties over 12 weeks in PBS or SBF but still retained their structural integrity. Coaxial scaffolds with and without HA exhibited gradual and sustained BMP-2 release and supported MSCs proliferation and differentiation with no significant difference between the two scaffolds types. These materials therefore show potential applications as bone tissue engineering scaffolds.