# Poly(lactic acid)-Based Electrospun Fibrous Structures for Biomedical Applications
## 8 Biomedical Applications of PLA-Based Nanofibrous Structures
### Tissue Engineering
#### 8.3.1. PLA Electrospun Structures for Musculoskeletal Tissue Engineering
The results verified that aligned nanofibers (AN) with smaller diameters had obvious advantages in promoting cell migration and proliferation and facilitating the osteogenic differentiation of BMSCs in comparison with random fibers. Scaffolds with randomly oriented fibers hinder effective cell infiltration (Figure 16a1-a8). In order to improve the biocompatibility of PLA scaffolds, some additives have been applied on the surface of electrospun fibers [132; 133]; for example, [PERSON] et al., coated with silica nanoparticles (SiNPs), with high surface area and good biocompatibility, the surface of porous PLLA fibrous membrane in order to improve better bone cell attachment (Figure 16b). The membrane was designed to serve as substrates of SiNPs for bone tissue engineering. To improve the coating strength of SiNPs on PLLA fibers, Dopamine (DOP) was used to modify the surface of PLLA fibers. Hydrophilicity and mechanical properties of PLLA/DOP/SiNP composite membranes were significantly improved due to the presence of SiNPs; they concluded that PLLA/DOP/SiNP membrane with improved cellular biocompatibility, and more cell adhesion and proliferation are promising materials for bone regeneration applications [132]. In another study, [PERSON] et al. [133] used surface grafting to modify the surface of PLA fibrous scaffold to better immobilize BMP-2 peptides liposomes on the surface of fibers (Figure 16c). The treated scaffolds showed higher attachment efficiency of liposomes. In another study, a polydopamine (pDA)-assisted coating strategy was used in order to immobilize bone morphogenetic protein-2 (BMP-2)-derived peptides on the surface of nano-hydroxyapatite/PLLA/gelatin (nHA/PLA/GEL) scaffolds (Figure 16d). In vitro and in vivo results showed that nanofibrous scaffolds containing nHA and BMP-2 peptides have suitable biocompatibility and osteoinductivity; they also showed sustained release ability, so they are excellent candidates in bone regenerative medicine [134]. Using blend electrospinning of PLA with other polymers, such as chitosan also has received attention in order to improve different properties of fibrous scaffold for bone tissue engineering application [72]; for example, [PERSON] et al. [137] mixed PLLA and bioactive lecithin to fabricate fibrous scaffolds, with improved cytocompatibility and hydrophilicity, where great interaction between PLLA/lecithin scaffolds and cells took place, resulting in cells being induced on scaffolds for keeping morphological shape and integrating with the fibers in order to develop a 3D network. [PERSON] et al. [138] developed a PLLA electrospun scaffold incorporated with Poly(3-hydroxybutyrate-co-3-hydroxyValerate) (PHBV) to improve the shape memory functionality and mechanical properties. PLLA-PHBV scaffold considerably promoted the osteogenic commitment in BMSCs with osteoinductive factors in a synergistic manner, which has a great potential to be used as a multifunctional 3D scaffold for bone regeneration. One of the important challenges in bone tissue engineering is the manufacturing of biomimetic scaffolds, which are able to fill the gap between porous structure requirements and mechanical strength. Although electrospinning technology develops nanofibrous structures similar to ECM, the restricted shapes and pore size of the electrospun mesh limits its application in bone tissue engineering; regarding this, [PERSON] et al. [140] combined electrospinning, freeze-drying, and crosslinking to fabricate a novel (3D) PLLA/regenerated cellulose (PLA/RC) scaffold (Figure 16e). Due to the presence of RC nanofibers, hydrophilicity and biological activity of the final scaffolds have been improved. PLA/RC scaffolds also exhibit excellent biomineralization ability in the SBF solution that can be considered as a promising scaffold bone tissue engineering application. Figure 16: Effect of fiber alignment on the morphology of BMSCs on electrospun membranes (**a\({}_{1}\)**–**a\({}_{4}\)**) Immunofluorescence images of AN, AM, RN and RM.