Breath figure (BF) is a phenomenon of water vapor comes into contact with cold surface (solid or liquid) and self-assembly, forming a set of fog droplets (Bormashenko, 2017). BF allows the fabrication of well-controlled microporous topography by rapidly evaporating polymer solutions in a humid atmosphere (Widawski et al., 1994; François et al., 1995; Pitois and François, 1999). Francois first reported the construction of honeycomb (HC) structured polymer films by BF in 1994 (Widawski et al., 1994). Since then, BF has attracted great research interest in fabricating polymer materials with microporous surface due to its simplicity, low cost, robust mechanism of pattern formation and flexibility of pattern tailoring (Bunz, 2006; Stenzel et al., 2006; Mansouri et al., 2013; Zhang et al., 2015).

The construction of polymer materials with HC morphology mainly include three steps (Huang et al., 2014): i) dissolve the polymer in a good organic solvent and cast the solution on a solid substrate. The organic solvent rapidly evaporates, decreasing the surface temperature of the solution from room temperature to near 0°C; ii) the water vapor in the air quickly nucleates and condenses on the cold surface of the solution to form small droplets; iii) the water droplets are assembled under the action of capillary force to form hexagonal arranged micropores with sizes ranging from hundreds of nanometers to several microns. As a result, polymer films with honeycomb-patterned microporous surface are fabricated with one step using BF (Figure 2).

Polymer films with honeycomb-patterned topography can enhance cell adhesion, spreading, proliferation, and differentiation. Wu et al. studied honeycomb-patterned films incorporated with other components for osteoblast cultivation (Wu et al., 2014). They fabricated honeycomb poly (l-lactide) (PLLA) films incorporated with nano-hydroxyapatite (nHA) (3 wt%, 5 wt%, and 7 wt%) and evaluated the effect of nHA on the self-assembly of honeycomb patterns on PLLA films. In order to investigate the effect of the honeycomb pattern and nHA on the cell, MC3T3-E1 mouse newborn calvaria preosteoblasts were cultured on the film. The porous structure on films effectively increased the surface contact area with proteins, resulting in enhanced serum and fibronectin protein adsorptions and accelerated cell proliferation. The honeycomb pores also enhanced cell differentiation, especially when incorporated with nHA, which can enhance the interactions between the cells and the serum protein and promote osteoblast adhesion. Yin et al. developed hydrophilic honeycomb-patterned PLA films via BF with the assistance of ionic surfactant dodecyltrimethylammonium chloride (DTAC) (Yin et al., 2019). DTAC was preferentially oriented at the solution-air interface with its cationic hydrophilic head group in the air. As a result, the interfacial tension between the solution and water was decreased, which can help stabilize the condensed water droplets during the BF process, leading to the formation of highly ordered honeycomb pattern and enhancement of PLA surface wettability. The surface morphology of the film can be readily regulated by adjusting the ratio of PLA to DTAC. The hydrophilic PLA films with honeycomb patterns can promote cell attachment when used as a scaffold and outperformed the regularly used cell adhesion material Poly-l-lysine (PLL) (Yin et al., 2019).

Phase-separation technique can be applied to produce 3-D porous materials. This process is based on the inducement of thermal treatment, which can lower the free energy of a homogeneous polymer solution and make it thermodynamically unstable and tend to separate into a continuous multiphase system (Zhou et al., 2012). The multiphase system consists of two phases, one with a high polymer concentration, i.e., polymer-rich phase and another one with a low polymer concentration, i.e., polymer-lean phase. Either the former or the later will separate from the solution as a dispersed phase. Upon the solvent evaporation, the polymer-rich phase solidifies to transform into a sponge-like structure, while the polymer-lean phase becomes a porous membrane (van de Witte et al., 1996; Guillen et al., 2011). The key of using phase separation method to fabricate self-assembled polymer materials is changing the Gibbs free energy in the polymer solution systems through certain ways (Kamide et al., 1993; Ismail et al., 2020). Based on the difference in the thermodynamic state of the polymer solution, the phase separation method is mainly divided into non-solvent induced phase separation (NIPS), thermally induced phase separation (TIPS) and vapour induced phase separation (VIPS) (Kim et al., 2016).

Electrospinning is one of the most used technologies for the preparation of fibrous membranes. The main preparation process is to prepare a small amount of spinning liquid and inject it into the spinning machine (Huang and Thomas, 2018). The main principle is to promote the surface of the spinning liquid through the high-voltage electric field to generate current, resulting in stretching and splitting of the spinning liquid and causing the liquid to move along the spiral trajectory to the receiving device and solidify into nanofibers (Khajavi and Abbasipour, 2012). By using this method, a large number of fibers overlapping each other are made to form a porous film (Khajavi and Abbasipour, 2012; Huang and Thomas, 2020). Electrospinning can be combined with phase separation technology to produce nanofibrous films with surface roughness at nanoscale (Rezabeigi and Demarquette, 2019; Huang and Thomas, 2020).

Chen X et al. prepared polycaprolactone (PCL)/PLA core-shell porous drug-carrying nanofibers using coaxial electrospinning technology and non-solvent-induced phase separation technique. Chloroform/DMSO was used as solvent/non-solvent for both the core and the shell layers. In the process of jet flow, chloroform in both layers was first evaporated, generating phase separation with the formation of polymer aggregation areas and non-solvent aggregation areas. Non-solvent DMSO was evaporated after chloroform evaporation, forming holes on the surface of the nanofibers. The nanofibers with pores of different sizes can slow down the drug burst release and increase the dissolution of hydrophobic drugs (Chen et al., 2021a).

Foaming process mainly include bubble nucleation, expansion and fixation (Li et al., 2018). Factors affecting PLA foaming include temperature, saturation pressure of the nucleation stage of the foaming, cooling rate of the stabilization stage, tensile viscosity, strength and crystallinity of the polymer melt, the type and amount of the blowing agent, etc. (Han et al., 1976; Ding et al., 2016; Tiwary et al., 2017). PLA stereoscopic foam composites have been used to fabricate stable micelles applied to drug delivery and tissue engineering scaffolds (Zhou et al., 2016; Kuang et al., 2017).

Kuang et al. used pressure-induced flow (PIF)-assisted foaming to produce PLLA foams with low-density and high porosity (Kuang et al., 2017). PLLA foams with high-strength, low-density and uniform cellular morphology was produced. Long-term culture of mouse embryonic fibroblast cells (MEFs) demonstrated that the open-cellular PLLA scaffold provided prominent advantages such as enhanced cell adhesion and proliferation and improved nutrient transportation (Kuang et al., 2017).

PLA microcapsules, i.e., oil-water-oil (W1/O/W2) systems are prepared by double Pickering microemulsion method. The aqueous phase W) can carry hydrophilic drugs, while PLA is used as an oil phase O) to efficiently embed hydrophobic drugs. For drug-targeted drug release, tissue culture (Zhu et al., 2018). Guo et al. prepared PLA microcapsules by double Pickering emulsion method, using HA and GO as stabilizers for the inner and outer aqueous phases, respectively, the aqueous phase and the oil phase can be loaded with hydrophilic and hydrophobic drugs, respectively, and different layers of drugs can achieve segmented release (Guo et al., 2017). The microcapsular surface promotes initial cell attachment, leading to increased cell activity, while the hollow microcapsule structure allows nutrients and gases to circulate within the structure, making it suitable for cell proliferation, and its cladding structure also facilitates drug-controlled release.

In summary, above methods can fabricate PLA materials applied to medical field. BF is a simple and easy method to construct PLA biomaterial with microporous surface structures. But it is difficult to precisely control the size of the micropores (Bormashenko, 2017). Phase separation can produce sponge-like structure suits for cell culture, but it has disadvantages of energy inefficiency and non-suitability for large-scale production (Szewczyk and Stachewicz, 2020; Chen et al., 2021b). Electrospinning technology can industrially produce porous PLA membranes, but the production efficiency is relatively low, the pore size distribution is wide, and the mechanical properties of the fibers are relatively poor (Khorshidi et al., 2016; Lin et al., 2020). Foaming can produce materials with low-density and high porosity, but the foam has loose structure and non-suitability for produce bone scaffold. Double Pickering microemulsion can prepare microcapsules that are able to efficiently embed hydrophobic drugs. The microstructures fabricated above will promote cell attachment and provide anchorage points to the cell, store up the necessary nutrient or medicine and realize the release of loaded medicine.