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The repair of segmental bone defects caused by traumatic injury or pathological diseases remains a substantial challenge in clinic. Poly-l-lactic acid (PLLA) is recognized as one potential bone substitute material due to its natural biodegradability and excellent biocompatibility. Nevertheless, it still faces several fundamental puzzles including insufficient mechanical properties, slow degradation and poor osteogenic activity. To address these issues, the corresponding strategies were thoroughly explored in this review. Regulation of molecular weight and crystallization, as well as the control of crack propagation were the mainstream methods to improve the mechanical properties of PLLA, whereas surface medication and polymer blending was commonly adopted to regulate the degradation behavior. To achieve desirable tissue regeneration ability, the combination of physical stimulation (electric and magnetic) brings about a new and attractive solution, since it is able to mimic the electro-magnetic microenvironment of human body. Furthermore, future research directions are proposed from the prospects of fabrication process, dynamic degradation and multifunctional application. This review aims to offer deep insights and meaningful guidelines for future study of PLLA as implants.

Graphical Abstract

Nerve guidance conduits with favorable electrical conductivity were highly desired in peripheral nerve repair since nerve was natural electro-active tissue. MXene was an appealing candidate in endowing polymeric guidance conduits with electrical conductivity, yet its superiority was extremely constrained by its discrete distribution, incapable forming contiguous conduction channels in matrix. Herein, an efficient conductive nerve guidance conduit with three-dimensional continuous conductive network structure was constructed by prior powder design and laser additive manufacturing. Specifically, MXene was coated on poly-L-lactic acid (PLLA) particle surface by ultrasonic-assisted solution mixing and thus MXene was enriched at interfacial regions among adjacent polymer particles to form continuous MXene conductive network. More ingeniously, benefiting from the unique shearing-free and confined-flowing forming characteristic of laser additive manufacturing, not only network structure was retained as well as MXene contact became more tightly, which provided a continuous channel for rapid charge transfer. Results demonstrated that the conduits with 3.5 vol% MXene exhibited a continuous conductive network structure, resulting in an excellent electrical conductivity of 4.53 S/m, which was in appropriate conductive range of nerve growth (1–10 S/m). Cell evaluation confirmed the conduits significantly promoted cell proliferation, differential and neurite outgrowth. Therefore, this work not only illustrated the feasibility of additive manufacturing in constructing conduits with three-dimensional continuous conductive network structure, but also created a powerful strategy for fabricating desirable conductive nerve guidance conduits.

Polyvinylidene fluoride (PVDF)/barium titanate (BaTiO3) composites are becoming increasingly attractive in bone repair since it combines the advantage of polymer flexibility and ceramic piezoelectric constant. Herein, silver (Ag) nanoparticles were decorated on polydopamine functioned BaTiO3(Ag-pBT) by in situ growth. Then the strawberry-like structured Ag-pBT nanoparticles were introduced into PVDF scaffold fabricated by selective laser sintering. On one hand, Ag nanoparticles would act as a conductive phase to enhance the strength of the polarized electric field on BaTiO3, thereby forcing more domains to be aligned in the direction of the electric field and make piezoelectric effect of BaTiO3fully play in composite scaffold. On the other hand, Ag nanoparticles would attack multiple targets in bacteria by release of Ag+and production of reactive oxygen species. In fact, the antibacterial activity is highly desirable for bone repair. Results demonstrated that the PVDF/4Ag-pBT scaffold exhibited enhanced piezoelectric properties with output current and voltage increased by 50% and 40% than that of PVDF/pBT, respectively. In vitrocell culture confirmed that the enhanced electric output further promoted cell proliferation and differentiation. Meanwhile, the scaffold presented robust antibacterial activity against E.coli.

Inefficient bone regeneration of self‐hardening calcium phosphate cement (CPC) increases the demand for interconnected macropores and osteogenesis‐stimulated substances. It remains a challenge to fabricate porous CPC with interconnected macropores while maintaining its advantages, such as plasticity. Herein, pastes containing CPC and wollastonite (WS) are infiltrated into a 3D plotted poly(lactic‐co‐glycolic acid) (PLGA) network to fabricate plastic CPC‐based composite cement (PLGA/WS/CPC). The PLGA/WS/CPC recovers the plasticity of CPC after being heated above the glass transition temperature of PLGA. The presence of the 3D PLGA network significantly increases the flexibility of CPC in prophase and generates 3D interconnected macropores in situ upon its degradation. The addition of WS is helpful to improve the attachment, proliferation, and osteogenic differentiation of mouse bone marrow stromal cells in vitro. The in vivo experimental results indicate that PLGA/WS/CPC promotes rapid angiogenesis and bone formation. Therefore, the plastic CPC‐based composite cement with a 3D PLGA network and wollastonite shows an obviously improved efficiency for repairing bone defects and is expected to facilitate the wider application of CPC in the clinic. A calcium phosphate–based composite cementis successfully constructed by infiltrating the cement pastes into a 3D PLGA network prepared by the 3D plotting technique, and in vivo experimental results show that the composites promote fast angiogenesis and bone formation. This modification strategy is expected to facilitate the wider application of calcium phosphate cement in clinic.