Poly-L-lactic acid (PLLA) is widely used in bone scaffold engineering due to its favorable biocompatibility, biodegradability, and processability. However, its mechanical properties are limited by insufficient crystallinity during fabrication. Moreover, bone repair is often accompanied by early bacterial infection and local pH reduction, which challenge the antibacterial effect, osteogenic capacity and structural stability of PLLA scaffolds. Herein, PLLA and hydroxyapatite (HA) are melt-blended into PLLA/HA (PHA). followed by self-polymerization of polydopamine (PDA) and electrostatic adsorption sodium nitroprusside of (SNP). The composite is then prepared into a PHA@PDA-SNP scaffold, with an outer Haversian canal layer and inner Gyroid-perforated. Ingeniously, the scaffold utilizes photothermal produced by near-infrared light to cleave biofilm and the FeNO bond in SNP, promoting NO release and entry into bacteria. Meanwhile, thermal can activate HSP70, synergizing with Ca2+ and PO4 3- released by PHA to boost osteogenic differentiation. Moreover, the amine groups retained during the oxidation process of PDA can weaken the acidic environment and enhance scaffold stability. Results show that the bone scaffold mimics the natural bone structure with high compressive strength (162.9 MPa) by biomimetic manufacturing. Scaffold exhibits cell osteogenic differentiation as evidenced by a 70% upregulation of HSP70 and Ca2+ influx, and a 4.5-fold increase of ALP and ARS. Scaffold utilizes photothermal and NO to achieve antibacterial rates of 97.4% and 98.2% against S. aureus and E. coli, respectively.

Bacterial infection following endometrial injury would delay tissue regeneration and further progress to endometritis and other reproductive disorders. Photodynamic therapy (PDT) is a promising bacterial strategy in the postantibiotic era. However, its therapeutic efficacy is often limited by the rapid recombination of photogenerated charge carriers and the limited penetration depth of visible excitation light. In this study, we report a previously unexplored up-conversion-mediated, Type I dominant photodynamic antibacterial uterine scaffold specifically designed for infection-associated endometrial injury. The core innovation lies in the construction of a Schottky Ag0-Ag2S heterojunction on the surface of NaYF4:Yb,Tm nanoparticles using ZIF-8 as a sacrificial precursor, which enabled highly efficient charge separation and oxygen-independent hydroxyl radical generation, effectively overcoming the inherent oxygen dependence and compromised performance of conventional Type II PDT under hypoxic uterine conditions. The upcon-version core further enables deep-tissue-penetrable NIR activation, addressing the poor penetration of visible light. Moreover, beyond instantaneous PDT, the dynamic release of Ag+ ions provides synergistic bactericidal activity, enabling spatiotemporally coordinated biofilm disruption. Importantly, these nanostructures were incorporated into patient-customizable, biodegradable PLLA scaffolds fabricated by selective laser sintering, achieving simultaneous antibacterial therapy and endometrial regeneration in a single platform. Collectively, the integration of an oxygen-independent PDT mechanism, MOF-templated heterojunction engineering, and 3D printed personalized uterine implants constitutes a comprehensive therapeutic strategy not previously reported for treating infection and endometrial injury.

Thermoelectric materials enabled thermoelectric-reactive oxygen species (ROS) conversion under temperature gradients, offering a promising strategy for suppressing postoperative recurrence of bone tumors and associated bacterial infections. However, their clinical translation was hindered by the inability to achieve spatiotemporally controlled ROS release within bone tissue. To address this, a magnetothermal-thermoelectric heterojunction (Bi2Te3-MnFe2O4) was constructed by in situ growth of manganese ferrite (MnFe2O4) on bismuth telluride (Bi2Te3) nanosheets, and was then incorporated into poly-L-lactic acid (PLLA) scaffold using additive manufacturing. Under an alternating magnetic field, the magnetothermal effect of MnFe2O4 induced a localized temperature increase, which activated the thermoelectric effect of Bi2Te3. This process drove the separation of electron-hole pairs and catalyzed ROS generation to antitumor and antibacterial. Furthermore, the multivalent metal ions (Mn2+/Mn3+ and Fe2+/Fe3+) in MnFe2O4 mediated Fenton-like reactions, further enhancing ROS production and depleting glutathione via chemodynamic therapy. The magnetothermal heating also accelerated the kinetics of these processes, forming a synergistic therapeutic outcome. Experimental results demonstrated that the ROS produced by the scaffold induced mitochondrial dysfunction and apoptosis in tumor cells, and effectively killed bacteria by causing intracellular content leakage. This study integrated the magnetothermal, thermoelectric, and chemodynamic effects into a bone scaffold, providing an innovative strategy for comprehensive postoperative treatment of bone tumors.

Photodynamic therapy, as a minimally invasive treatment, selectively and optically damaged skin tumor cells through the generation of reactive oxygen species (ROS). However, its antitumor efficacy is limited by the rapid recombination of electron-hole pair in photosensitizers. In this work, a rare-earth lanthanide-doped titanium dioxide nanosystem was successfully developed via a co-coprecipitation method. In this nanosystem, lanthanide doping induced lattice distortion and generated oxygen vacancy defects, effectively suppressing electron-hole pair recombination. Furthermore, the unique electronic structure of the lanthanide dopant modulated the band positions and Fermi level of titanium dioxide, thereby narrowing the bandgap and broadening its optical absorption spectrum. Subsequently, the nanosystem was incorporated into a poly-L-lactic acid scaffold by selective laser sintering. Photoelectrochemical and ROS analyses revealed significant enhancement in electron-hole pair separation and a marked increase in ROS generation. Density functional theory calculations further confirmed that the reduced bandgap contributed to the improved photocatalytic performance of titanium dioxide. In vitro cell experiments demonstrated that this photodynamic therapy platform achieved an 82.4 % inhibition rate of skin tumour growth. Overall, this work presents a feasible strategy to enhance the therapeutic efficacy of tumour photodynamic therapy.

Thermoelectric material could realize the thermal-electricity-reactive oxygen species (ROS) conversion under temperature gradient, being considered a promising candidate for tumor therapy. Nevertheless, it required exogenous excitation such as light irradiation, causing difficultity in achieving on-demand therapy. Herein, a tumor microenvironment responsive Bi2Te3-CaO2 nanohybrid was synthetized by in situ growing calcium peroxide (CaO2) nanoparticles on thermoelectric bismuth telluride (Bi2Te3) nanosheets, and then blended with poly-L-lactic acid (PLLA) to fabricate a PLLA/Bi2Te3-CaO2 scaffold. Once the acidic microenvironment of the tumor was sensed, the CaO2 would serve as an intelligent switch, releasing heat through rapid hydrolysis and triggering the thermoelectrocatalysis of Bi2Te3 to generate ROS, thereby achieving on-demand therapy. Results demonstrated that the scaffold exhibited rapid temperature rise and significant ROS catalytic formation ability in an acidic solution (pH 5.5), while no significant changes occurred in a neutral environment (pH 7.4). Annexin VFITC/PI staining and JC-1 assay demonstrated that the generated ROS could induce tumor apoptosis by reducing mitochondrial membrane potential. Besides, the fluorescent probe test revealed that CaO2 could also produce hydrogen peroxide (H2O2) and calcium ions (Ca2+) to interfere with intracellular Ca2+, thereby further enhancing the antitumor effect. Overall, this work proposed a novel perspective for on-demand antitumor therapy.

Photosensitizer-mediated photodynamic therapy (PDT) enables wireless tumor inactivation by releasing cytotoxic reactive oxygen species (ROS). Nevertheless, the activation of conventional photosensitizers typically depends on visible light with limited tissue penetration, thereby restricting their therapeutic efficacy in deep-seated tumors. To overcome this limitation, an upconversion implant was engineered to function as a flexible internal light-emitting device by converting deeply penetrating near-infrared-I (NIR-I) light into visible light. Specifically, a composite PDT nanosystem was constructed by linking NaYF4:Yb,Er upconversion nanoparticles with the rose bengal photosensitizer-whose emission and absorption spectra are well-matched-using polyvinylpyrrolidone (PVP) as a molecular bridge. This PDT nanosystem was subsequently incorporated into poly-L-lactic acid (PLLA) scaffolds fabricated via selective laser sintering. Under 980 nm laser irradiation, the upconversion implant was capable of wirelessly emitting upconverted visible light through more than 2 cm of an in vitro tissue model and generating abundant ROS via the photodynamic effect. In vitro cell experiments demonstrated that the system effectively eliminated tumor cells by damaging the cell membrane and cellular genetic material. These results suggest that the scaffolds possess significant potential as anti-tumor tissue implants and offer a promising avenue for the development of innovative tumor treatment strategies.

Although photothermal therapy is widely employed for tumor treatment because of its high tumor cell selectivity and low apoptosis resistance, heat-shock proteins (HSPs) impart resistance to heat-induced apoptosis in tumor cells, thus diminishing the therapeutic effectiveness. To this end, tin selenide (SnSe) was grown in situ on reduced graphene oxide (rGO) nanosheets to construct a photothermal-thermoelectric SnSe/rGO nanosystem. The rGO component converted near-infrared light energy into localized thermal energy, resulting in the thermal ablation of tumor cells. Meanwhile, SnSe converted temperature fluctuations into pyroelectric charges, which interacted with surrounding O-2 molecules to generate reactive oxygen species that oxidized the amino acids on the HSPs, which changed the protein conformation and functionally damaged the tumor cells. In addition, rGO functioned as an efficient electron acceptor to increase electron mobility, thus enhancing the thermoelectric conversion efficiency of SnSe. Then, the SnSe/rGO nanosystem was incorporated into a poly-l-lactic acid bone scaffold to prevent tumor recurrence. Results showed that the composite scaffold not only exhibited good photothermal and thermoelectric effects. In vitro cell tests demonstrated that the scaffold generated O-1(2) based on temperature fluctuations and the antitumor rate reached 86.6% against osteosarcoma MG-63 cells.

Extensive research on zeolitic imidazolate framework (ZIF-8) and its derivatives has highlighted their unique properties in nanomedicine. ZIF-8 exhibits advantages such as pH-responsive dissolution, easy surface functionalization, and efficient drug loading, making it an ideal nanosystem for intelligent drug delivery and phototherapy. These characteristics have sparked significant interest in its potential applications in tissue regeneration, particularly in bone, skin, and nerve regeneration. This review provides a comprehensive assessment of ZIF-8’s feasibility in tissue engineering, encompassing material synthesis, performance testing, and the development of multifunctional nanosystems. Furthermore, the latest advancements in the field, as well as potential limitations and future prospects, are discussed. Overall, this review emphasizes the latest developments in ZIF-8 in tissue engineering and highlights the potential of its multifunctional nanoplatforms for effective complex tissue repair.

Cuprous oxide (Cu2O) has great potential in photodynamic therapy for implant-associated infections due to its good biocompatibility and photoelectric properties. Nevertheless, the rapid recombination of electrons and holes weakens its photodynamic antibacterial effect. In this work, a new nanosystem (Cu2O@rGO) with excellent photodynamic performance was designed via the in situ growth of Cu2O on reduced graphene oxide (rGO). Specifically, rGO with lower Fermi levels served as an electron trap to capture photoexcited electrons from Cu2O, thereby promoting electron-hole separation. More importantly, the surface of rGO could quickly transfer electrons from Cu2O owing to its excellent conductivity, thus efficiently suppressing the recombination of electron-hole pairs. Subsequently, the Cu2O@rGO nanoparticle was introduced into poly-L-lactic acid (PLLA) powder to prepare PLLA/Cu2O@rGO porous scaffolds through selective laser sintering. Photochemical analysis showed that the photocurrent of Cu2O@rGO increased by about two times after the incorporation of GO nanosheets, thus enhancing the efficiency of photogenerated charge carriers and promoting electron-hole separation. Moreover, the ROS production of the PLLA/Cu2O@rGO scaffold was significantly increased by about two times as compared with that of the PLLA/Cu2O scaffold. The antibacterial results showed that PLLA/Cu2O@rGO possessed antibacterial rates of 83.7% and 81.3% against Escherichia coli and Staphylococcus aureus, respectively. In summary, this work provides an effective strategy for combating implant-related infections.

CeO2 nanozymes have garnered significant attention in chemodynamic therapy due to their peroxidase-like activity and ability to deplete glutathione. However, their catalytic efficiency is constrained by the low conversion rate of Ce3+/Ce4+. To overcome this limitation, the electron transfer was accelerated by introducing the transition metal Mn atom as a valence electron donor through lattice charge transfer. In detail, we introduced Ce1-xMnxO2 into the poly-L-lactic acid (PLLA) scaffold fabricated by selective laser sintering. The conversion from Ce3+ to Ce4+ promoted the decomposition of H2O2 within the tumor microenvironment to generate hydroxyl radicals with high oxidative activity, consequently inducing oxidative stress. The conversion from Ce4+ to Ce3+ depleted intracellular antioxidant glutathione, disrupting redox balance in tumor cells. This continuous redox cycle ultimately triggered apoptosis in tumor cells. Using a first-principles Hubbard-corrected approximate density-functional method, the analysis of the electron band structure revealed the presence of donor energy levels within the bandgap of Ce1-xMnxO2, enabling electron transfer channels around 0.645 eV. Electrochemical experiments confirmed that Ce0.8Mn0.2O2 significantly reduced the activation overpotential from 0.907 V to 0.646 V, enhancing its redox capacity. As a result, the scaffold exhibited a threefold increase in tumor-killing rate. These findings highlight the immense potential of CeO2 nanozymes in enhancing chemodynamic therapy for effective tumor treatment.

The integration of hydroxyapatite (HA) with broad-spectrum bactericidal nano-silver within biopolymer-based bone scaffolds not only promotes new bone growth, but also effectively prevents bacterial infections. However, there are problems such as a poor interface compatibility and easy agglomeration. In this project, zeolitic imidazolate frameworks (ZIF-8) were grown in situ on nano-HA to construct a core–shell structure, and silver was loaded into the ZIF-8 shell through ion exchange. Finally, the core–shell structure (HA@Ag) was composited with polylactic acid (PLLA) to prepare bone scaffolds. In this case, the metal zinc ions of ZIF-8 could form ionic bonds with the phosphate groups of HA by replacing calcium ions, and the imidazole ligands of ZIF-8 could form hydrogen bonds with the carboxyl groups of the PLLA, thus enhancing the interface compatibility between the biopolymers and ceramics. Additionally, the frame structure of MOFs enabled controlling the release of silver ions to achieve a long-term antibacterial performance. The test results showed that the HA@Ag nanoparticles endowed the scaffold with good antibacterial and osteogenic activity. Significantly, the HA@Ag naoaprticle exhibited a good interfacial compatibility with the PLLA matrix and could be relatively evenly dispersed within the matrix. Moreover, the HA@ZIF-8 also effectively enhanced the mechanical strength and degradation rate of the PLLA scaffold.

Intrauterine adhesion (IUA) is a common gynecological disease caused by endometrial injury, which might result in abnormal menstruation, miscarriage, and even fetal deaths. Nevertheless, existing treatment strategies such as intrauterine device and uterine cavity balloons only provide a physical barrier, and not circumvent inflammation of endometrial microenvironment and retrograde infection. In this study, a slow-controlled bifunctional nano-structure was developed via encapsulating hyaluronic acid (HA) on surface of silver-metal organic framework (Ag-MOF), and then loaded in poly lactic-co-glycolic acid scaffold to prevent IUA. In therapy, macro-molecule of HA provided anti-inflammatory function by the adjustment of signal transduction pathways of macrophage surface receptors, whereas Ag-MOF inactivated bacteria by destroying bacterial membrane and producing reactive oxygen. Significantly, the coated HA effectively avoided burst release of Ag+, thus achieving long-term antibacterial property and good biocompatibility. Antibacterial results showed antibacterial rate of the scaffold reached 87.8 % against staphylococcus aureus. Anti-inflammatory assays showed that the scaffold inhibited the release of inflammatory cytokines and promoted the release of anti-inflammatory cytokines. Moreover, in vitro cell tests revealed that the scaffold effectively inhibited fibroblast growth, indicating its good ability to prevent IUA. Taken together, the scaffold may be a promising candidate for IUA treatment.

A NH2-MXene/PLLA nerve conduit with a conductive network structure is constructed by laser additive manufacturing, which can generate electrical signals driven by electromagnetic induction, and the generated electrical signals can promote the differentiation of nerve cells.

Bacterial infection with high morbidity (>30%) seriously affects the defect's healing after bone transplantation. To this end, chemotherapy and photothermal therapy have been utilized for antibacterial treatment owing to their high selectivity and minimal toxicity. However, they also face several dilemmas. For example, bacterial biofilms prevented the penetration of antibacterial agents and local temperatures (over 70 °C) caused by the photothermal therapy damaged normal tissue. Herein, a co-dispersion nanosystem with chemo-photothermal function was constructed via the in situ growth of zeolitic imidazolate framework-8 (ZIF-8) on graphene oxide (GO) nanosheets. In this nanosystem, GO generates a local temperature (∼50 °C) to increase the permeability of a bacterial biofilm under near-infrared laser irradiation. Then, Zn ions released by ZIF-8 seized this chance to react with the bacterial membrane and inactivate it, thus realizing efficient sterilization in a low-temperature environment. This antibacterial system was incorporated into a poly-l-lactic acid scaffold for bone repair. Results showed that the scaffold showed a high antibacterial rate of 85% against both Escherichia coli and Staphylococcus aureus. In vitro cell tests showed that the scaffold promoted cell proliferation.

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.

Zeolitic imidazolate framework-8 (ZIF-8) nano-particles are able to act as effective reinforcements to enhance the overall performance of a poly-L-lactic acid (PLLA) scaffold due to its interface compatibility and natural degradability. Nevertheless, the fast degradation of ZIF-8 would release excessive zinc ions, which produces adverse effects on natural cell growth. In this study, a core-shell-structured nanoparticle, in which ZIF served as a core and hydroxyapatite (HA) served as a shell, was constructed by polydopamine (PDA)-induced in situ growth of HA on ZIF-8 nanoparticles, aiming to control the zinc ion release. Then, the core-shell-structured nanoparticle (ZIF-8@PDA-HA) was introduced into the PLLA scaffold using selective laser sintering. Results showed that the zinc ion concentration for the PLLA/ZIF-8@ PDA-HA scaffold decreased by 65.3% after 28 days of immersion, as compared with the PLLA/ZIF-8 scaffold. Moreover, the in situ synthesized HA possessed superior bioactivity, which effectively enhanced the mineralization ability of scaffolds and promoted cell adhesion, proliferation, and differentiation.

Poly l-lactic acid (PLLA) was limited in the further orthopaedic application due to its insufficient mechanical property and poor bioactivity. Graphene oxide (GO) is an effective reinforcement, whereas silicon-doped hydroxyapatite (Si-HA) possesses excellent bioactivity, but either GO or Si-HA tends to aggregate in PLLA matrix. In this study, a GO@Si-HA nanosystem was achieved by in-situ growth of Si-HA on GO, and then incorporated into PLLA scaffold fabricated by laser sintering technology. On one hand, Si-HA on the surface of GO effectively prevented the aggregation of GO by acting as a barrier between GO nanosheets. On the other hand, GO hindered the aggregation of Si-HA by means of anchoring Si-HA. Results displayed that the compressive strength and modulus of the PLLA/GO@Si-HA composite scaffold were enhanced by 85% and 120%, respectively. Meanwhile, the scaffold exhibited significantly improved bioactivity, and consequently promoted cell adhesion, proliferation and differentiation. The developed PLLA/GO@Si-HA composite scaffold with excellent mechanical properties and superior bioactivity could serve as a promising substitute for bone repairing.

Biopolymer scaffold is expected to generate electrical stimulation, aiming to mimic an electrical microenvironment to promote cell growth. In this work, graphene and barium titanate (BT) was introduced into selective laser sintered poly-l-lactic acid (PLLA) scaffold. BT as one piezoelectric ceramic was used as the piezoelectric source, whereas graphene served as superior conductive filler. Significantly, the incorporated graphene enhanced the electrical conductivity and thereby increased the electric field strength applied on BT nanoparticles during poling. In this case, more electric domain within BT rearranged along the poling field direction, thus promoting the piezoelectric response of the composites. Results showed that the PLLA/BT/graphene scaffold exhibited relatively high output voltage of 1.4 V and current of 10 nA. Cells tests proved that these electrical signals considerably promoted cell proliferation and differentiation. Moreover, the scaffold exhibited improved mechanical properties due to the rigid particle enhancement effect and increased crystallinity.