![]() PLCL nanofibers have been demonstrated to support the growth and proliferation of many cell types while showing inadequate cell affinity due to its hydrophobicity and the absence of recognition sites for cell adhesion 26. Poly(L-lactic acid-co-ε-caprolactone) (PLCL) are a copolymer of L-lactic acid and ε-caprolactone whose mechanical properties and degradation rate can be controlled and changed by the relative composition of monomers 25. SF has been extensively used in biomedical applications such as sutures, drug delivery matrices, and 3D scaffolds for ligament, bone, cartilage, fat, neural, cardiac, ocular, bladder and vasculature engineering 24. ![]() Silk fibroin (SF) is a promising protein-based biomaterial for tissue engineering which has shown excellent mechanical properties, slow degradation, well biocompatibility and low inflammatory response compared to collagen and poly lactic acid 23. With the promise of controllable fibrogenic commitment of MSCs, treatment of pelvic floor disorders could be brought forward by deploying a biodegradable electrospun mesh to deliver therapeutic cells to enhance formation of new connective tissue that will take over mechanical load when the mesh degrades.Ĭonsidering FGF-2 and CTGF with individual functions on improving MSCs survival and proliferation and steering MSCs to a fibroblastic commitment, respectively, a model of dual delivery device at the wound region for combination treatments of FGF-2 and CTGF would draw attention for their synergistic effect on MSCs and broaden their clinical potential for pelvic floor connective tissue regeneration. To this date, no efficient treatment without side effects or risk of recurrence is available. The lifetime risk for undergoing POP surgery is estimated to 11.1–19% with a risk of further reoperation up to 30% 22. This disorder can lead to pelvic organ prolapse (POP) seen as a herniation of the bladder, uterus or intestines into the vagina 21. Half of the female population over the age of 50 experiences disorders of the pelvic floor caused by weakening and rupture of supportive connective tissue sheet or fascia 20. 19 both demonstrated CTGF loaded 3D scaffold was capable of fostering fibroblastic differentiation in vitro. Our previous study 18 and the study reported by Tong et al. ![]() Until recently, connective tissue growth factor (CTGF) or CCN2, a member of CCN family 15 has been identified to sufficiently direct MSCs differentiation towards fibroblasts 16 and promote connective tissue healing in a rodent injury model 17. In association with TGFβ1, insulin-like growth factor-I (IGF-I) and bone morphogenic protein 2 (BMP-2) were known to induce the differentiation of MSCs into chondrocytes 14. The differentiation of MSCs into mesenchymal lineage is known to be controlled by diverse transcription factors and signaling cascades such as Hedgehog 11, NEL-like protein 1 (NELL-1) 12 and β catenin-dependent Wnt 13. Previous studies have shown FGF-2 or basic fibroblast growth factor (b-FGF) to be able to increase rat, rabbit, canine and human MSCs proliferation and maintains their multilineage differentiation potential during in vitro expansion 7, 8, 9, 10.Īpart from the expansion, the prospect of controlling MSC differentiation is a crucial regulatory and clinical requirement. ![]() Fibroblast growth factors (FGFs) are a family of growth factors involved in many functions such as cell proliferation, migration, and differentiation and are critically important in tissue development, maintenance and wound repair 6. Some cytokines have been identified to enhance the proliferation of MSCs, such as Platelet-derived growth factor (PDGF) through the activation of c-Jun N-terminal kinase (JNK) signaling 4, Transforming growth factor β1 (TGFβ1) inducing the rapid nuclear translocation of β-catenin in a Smad3-dependent manner 5. However, MSCs survival and incorporation at the graft are still crucial issues for transplantations. These characteristics make them an attractive candidate for biological cell-based tissue repair approaches 3. It has also been suggested that they can modulate the host immune responses when transplanted 2. Mesenchymal stem cells (MSCs) can be efficiently isolated from adult bone marrow, are capable of extended proliferation and hold the potential to differentiate into mesenchymal lineages including osteoblasts, chondrocytes, and adipocytes 1. ![]()
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