Injectable Scaffold with electrospun material

Electrospun nanofibers have been shown to be a good substrate for cell adhesion and proliferation. Having the nanofibers as an injectable scaffold will expands its utilization in non-invasive surgery. Less intrusive and traumatic surgical technique and technology is growing in popularity due to reduced risk of infection, excessive bleeding and scar formation. It is common to use as small incision as possible for this purpose and replacement scaffolds needs to be injectable for delivery. Having nanofibers in injectable form has the potential to enhance recovery while reducing surgical risk

Several studies have shown favourable cell response when electrospun fibres are present in the hydrogel. Baylan et al (2013) showed that when electrospun polycaprolactone nanofibers was added into collagen solution and seeded with MC3T3-E1 (pre-osteoblastic cells), collagen fibrils observed under SEM was found to be thinnest with 6 w/v% PCL nanofibers added at 5 mm while without nanofibers, the collagen fibers were found to be 500 nm. Scaffold shrinkage was also found to be lowest and mineral secretion the greatest with 6 w/v% PCL nanofibers added to collagen solution compared to pure collagen and with 1w/v% PCL nanofibers added.

Researchers have come out with various methods for using electrospun fibers as injectable material. Electrospun fibres are usually incorporated into hydrogel or paste for use as an injectable scaffold. The fibres may be chopped into short fibres or used as it is for mixing. The use of chopped fibres instead of as-spun membrane can be easily understood to preserve good flow of the injectable material. Although individual electrospun fiber is highly malleable due to its high aspect ratio, entanglement of the fibres in its membrane form turns it into a rigid structure. There are several ways of converting the as-spun fibres into short strands. The most basic method involves physically cutting the fibres [Jiang et al 2013] or grinding them. Other methods such as chemical cleaving of the molecular bonds [Kim et al 2008] have also been used.

Instead of individual short strand fibres, the electrospun membrane may also be chopped into small pieces or flakes for mixing into hydrogel or binding agents. This has been demonstrated in the construction of 3D scaffold but it can also be easily used in injectable scaffold. Such form is easier to obtain consistently compared to short strand fibres. Bao et al (2011) cut out electrospun poly(D,L-lactide-co-glycolide) (PLGA) membrane into small pieces measuring 3 mm by 3 mm. These small pieces of fibrous membrane were mixed with calcium phosphate cement (CPC) powder and chitosan lactate to form an injectable paste. For the fiber filled paste to be injectable through a 10-gauge needle, the fiber volume fractions cannot exceed 10%. hUCMSC cultured on CPC scaffold containing 10% fibers showed increased ALP, OC, collagen expression and mineralization compared to pure CPC.

Electrospun scaffold may also be used directly for mixing with hydrogel without chopping into small pieces or short strands. The key challenge is to achieve an electrospun fiber form that is able to flow through a small diameter. This typically uses low volume of fibres in the mixture so that there are fewer entanglements between fibres during mixing and injection. Post-electrospinning process such as ultra-sonication has been successfully used to open up electrospun fiber scaffold volume. This will facilitate mixing with hydrogel. Baylan et al (2013) used just 6 w/v% PCL nanofibers in collagen solution and this small addition is sufficient to significantly reduce scaffold shrinkage and induce favourable cell response.

It is possible to construct injectable electrospun fibers membranes without the additional step of mixing the membrane with hydrogel. Amagat et al (2023) demonstrated this by electrospinning a core-shell fiber with a hydrogel shell. Since hydrogel is generally mechanically weak, the core-shell fiber structure was used to introduce a stronger material to strengthen the resultant fiber. For most injectable electrospun membranes, a hydrogel was used to encapsulate the fibers. Therefore, in this core-shell fiber, the stronger poly(lactide-co-ε-caprolactone) (PLCL) was used as the core material and methacrylated gelatin (GelMA)/alginate hydrogel was the shell. Any other active ingredients were added to the shell material. The membrane with triangle and square-shaped mesh sized 0.72 or 1 cm², respectively, was shown to support injection through inhalation and injection steps connected to a glass tube (inner diameter 0.9 mm). Similarly, the membrane can be ejected and inhalated back into a 20 G needle.