Potential use of electrospun fibers in soft tissue volume filling

Currently, it is a challenge to replace lost adipose tissues as the space is often quickly filled up by collagen fibers. Procedures such as breast reconstruction or augmentation will benefit from the ability to generate stable adipose tissues. Electrospun fibers have been shown to facilitate cells adhesion and proliferation including adipocytes and preadipocytes. Smith et al (2007) conducted an in vitro study to investigate the immune response of cells to electrospun membrane of different materials. The antibody production of sheep splenocytes was quantified to determine their in vitro hemolytic antibody-forming cell response when exposed to the electrospun membranes. Materials investigated include non-electrospun ePTFE and electrospun membrane of nylon, polydioxanone (PDO), poly(glycolic acid) (PGA), poly(lactic acid) (PLA), and a 50:50 (v:v) blend of PDO and polycaprolactone (PCL). The results showed that electrospun PDO, PGA, PLA, PDO-PCL are immunosuppressive in the Mishell-Dutton assay (lower antibody production compared to cell cultured in media) while e-PTFE and nylon are not. A comprehensive in vitro study of the immune response to electrospun polydioxanone, elastin and their blends involving macrophage biochemical response, T-cell activity, Mishell-Dutton assay and others, demonstrated immunosuppression activity [Smith et al 2009]. Therefore electrospun fibers have the potential for use in soft tissue regeneration by reducing immune response and collagen deposition.

To expand soft tissue volume, one technique is to use a volume chamber to house pedicled flap. The volume chamber allows the pedicled flap to expand in volume without obstruction from surrounding host tissues. However, immune response within the chamber encourages the deposition of collagen fibers around the pedicled flap limiting its volume expansion. Since electrospun fibers have been shown to reduce immune response, this has been used to facilitate tissue expansion in the volume chamber. Luo et al (2016) tested this concept by lining the inner walls of a silicone volume chamber with electrospun polycaprolactone (PCL). In a rat model, a pedicled adipose flap was embedded into the chamber with and without electrospun PCL lining and these was inserted into both groins of the rat. From week 1, the volume increase of the flap was faster than the control. By week 8, the volume increase of both silicone chambers with and without PCL nanofibers lining has reached a plateau. Volume increase for the chamber with electrospun fibers was significantly better than the control which does not have nanofibers lining. The control group also consistently showed greater collagen deposition compared to the study group.

With a pedicled flap, larger incision is needed to shift the pedicled flap from another location. Further, a pedicled flap may not be readily available for the required site. In this case, alternative filler is needed. While fats may be transferred from another area and used as fillers, the implanted fats often lose its volume due to necrosis and breaking down of the tissue. Manufactured implantable scaffold may be used as fillers instead. Advances in electrospinning have seen the development of several techniques to produce bulk volume scaffolds instead of flat scaffold. Barker et al (2013) conducted an in vivo study for soft tissue regeneration using layers of electrospun membrane with and without cells seeded to form a 1 mm thick scaffold. The scaffolds were well tolerated by the recipients in the rat model with evidence of neovascularisation from 4 to 12 weeks. In the scaffold with fibroblast seeded, significantly greater amount of early neovascularisation was observed compared to the acellular scaffold. However, significant volume reduction of more than 50% was recorded for the scaffold. The scaffold was made from polycaprolactone (PCL)/collagen blend with significantly greater percentage weight ratio of PCL. Considering the known slow degradation of PCL, volume reduction in this case may be due to compression of the scaffold instead of degradation. In the same study, decellularized dermis implant from human and porcine showed less volume reduction in the first 8 weeks. A possible reason for this difference in volume reduction may be due to the pore size of the scaffolds. In decellularized dermis, the pore size may be much larger than the nanofibrous scaffolds. Large pore sizes allow migration of cells into the decellularized dermis and subsequent deposition of extracellular matrix (ECM) within the pores which supported its volume. In nanofibrous scaffold, there may be less ECM deposited within the scaffold. Capsule formation around the nanofibrous scaffold may also contribute to volume reduction over time.

To take advantage of the presence of tissue and to have a longer lasting scaffold to keep the volume intact, manufactured scaffold may be mixed with tissue bits. Clinical application of electrospun scaffold in soft tissue fillers may combine with current clinical procedures. Liposuction is a relatively common procedure to remove excess fats from the body. This source of fats may be used with electrospun scaffold as soft tissue fillers. A preliminary study using minced fats mixed with three-dimensional electrospun scaffold have shown that cells were still viable after 4 weeks of culture while cells in at the core of intact fat was no longer viable [Panneerselvan et al 2015]. Further, endothelial cells were also found to be viable in the tissue scaffold mixture and this may potentially accelerate the angiogenesis process. Xu et al (2014) did a comparison of electrospun three-dimensional structure, electrospun two-dimensional structure and commercial 3D scaffold. The 3D electrospun scaffold with adipose derived mesenchymal stem cells (ADMSC) demonstrates better distribution of cells and proliferation compared to two-dimensional scaffold. Investigation of adipogenic differentiation through Oil red O staining also showed more newly secreted fat by ADMSC on the 3D fibrous scaffold followed by 2D scaffold and the commercial 3D scaffold being the worst.

Bioartificial graft constructed from a mixed of minced fat tissues and electrospun 3D scaffold.