Fig. 1 Schematic diagram of polymer microneedles development

Fig. 2 Preparation method of microneedles. (A,B) Decompression pouring method. (A) Schematic diagram of the process for preparation of microneedles using concentration differences[20]; Schematic diagram of the process for manufacturing microneedles using DPFM (B-i); Electron microscopic images of microneedles (B-ii)[21]; (C) Hot embossing[22]. Schematic diagram of hot embossing (C-i); Scanning electron microscopic images of microneedles (C-ii); (D) Impregnation and coating method. Schematic diagram of the coating microneedle fabrication process[24]; (E,F) 3D printing method[26]. (E) The schematic illustration of the fabrication of MNs by FDM 3D printing and chemical etching; Optical images of MNs as FDM-fabricated (F-i) and after etching in KOH solution (Fii); SEM images of MNs as fabricated (F-iii) and after etching in KOH solution (F-iv)

Fig. 3 Characterization of polymer microneedle systems. (A,B) Mechanical properties of the microneedle system[28]. (A) Schematic diagram of stress modeling (H: initial height of microneedles; H': height of microneedle missing tip; r1: half the side length of the quadrilateral microneedle base; r2: initial half length of the tip of the quadrilateral micro pin; δ: displacement of microneedle; rδ: when the compression displacement is δ, the half length of the contact surface); (B) Displacement changes under different types of microneedles (* : p < 0.05;** : p < 0.01;*** : p < 0.001); (C,D) Drug delivery performance of the microneedle system. (C) microneedle administration method[31]; Bacteriostatic rate under different treatment modes (D-i); Schematic representation of SA, PIL-MN and SA-PIL-Mn for skin acne treatment in a mouse model (D-ii)[32]

Fig. 4 Trigger release mechanisms of different types of stimulation-responsive polymer microneedles

Fig. 5 Environmentally responsive polymer microneedles. (A) Photoresponsive polymer microneedle system. Schematic diagram of the preparation of 5-Fu-ICG-MPEG-PCL (A-i); Growth curves of A431 tumor-bearing mice in each group (mean ± standard deviation (n=5) “**” denotes P < 0.01) (A-ii); Near-infrared thermal effect of A431 tumor-bearing mice irradiated with 1 W/cm2 808nm laser for 5 min (A-iii)[40]; (B) Electrically responsive polymer microneedle system. MXene microneedle biosensor measurement method and signal processing potential peak (B-i); MXene microneedle biosensor application (B-ii)[45] ; (C) Magnetically responsive polymer microneedle system. magnetically driven capsules with multi-layer MN patches (C-i); The process of using a magnetically driven capsule to deliver a microneedle patch to a target lesion (C-ii)[50]; (D) Thermal responsive polymer microneedle system. Intent of gelatin-PNIPam microneedles for control of transdermal drug delivery (D-i); Drug release rates in different concentrations of H2O2 (D-ii); In vitro release rates of RS-GP microneedles at 37 ℃ (1), room temperature (2) and common gelatin microneedles at 37 ℃ (3) (D-iii)[52]; (E) Mechanical force responsive polymer microneedle system. Integration of medicine-equipped wearable devices with microneedle array patches (E-i); Changes in blood glucose levels of mice under different treatment methods (E-ii)[57]

Fig. 6 Stimulus-responsive polymer microneedles for physiological signals in vivo. (A) pH-responsive polymer microneedle system. Schematic diagram of ZIF-8 encapsulated microneedles (A-i); CCM release curves under different pH conditions (A-ii)[67]; (B) Glucose-responsive polymer microneedle system. The mechanism and in vitro performance of GRS glucagon delivery system (B-i); Changes in plasma glucagon concentrations in diabetic mice treated with the patch (B-ii)[70]; (C) Reactive oxygen reactive polymer microneedle system. Mechanism diagram of microneedles in response to H2O2 delivered MTX in the treatment of psoriasis (C-i); EGCG release rate of microneedles in vitro at different concentrations of H2O2 (C-ii)[74]; (D) Enzyme-responsive polymer microneedle system. Schematic diagram of the mechanism of microneedle lysis of biofilms in infected wound removal (D-i); left-handed release curves at different pH values and temperatures (D-ii)[82]

Fig. 7 Application of Stimulus-responsive polymer microneedle systems

Fig. 8 Transdermal delivery of stimulus-responsive polymer microneedles. (A) Tissue and organ therapy. Thermal images of MN applied to the back skin of rats before and after 1 W/cm2 NIR irradiation for 2 min (A-i); Oxygen release in different groups (control group, BP group, BP + Hb group and BP + Hb + NIR group) (A-ii);Representative photographs of different groups of skin wounds on days 0, 3, 5, 7 and 9 (A-iii)[88](B) Detection and sensing device application[91]. Diagram of the manufacturing process and detection mechanism of the glucose sensor (B-i); I(A)-t response curve in stirred PBS continuously supplemented with 0.2 mM glucose at 0.75 V (B-ii); 0.5 mM glucose, 0.025 mM AA, 0.5 mM glucose, 1 mM urea, 0.025 mM Gly, 0.5 mM glucose and 0.025 mM AP were added continuously at 0.75 V (B-iii); (C) Sample extraction application. Schematic diagram of conventional CTAB extraction and MN extraction (C-i); Image of tomato leaves after puncture and cut of microneedle patch (C-ii); The amount of DNA extracted by microneedle extraction method and CTAB extraction method (C-iii)[93]; (D) Whitening and anti-aging applications. Histological images of skin hair treated with control, HA and gelatin microneedles (D-i); Change rate of skin elasticity within 4 weeks before and after microneedle application (P<0.05) (D-ii)[99]; (E) Anti-hair loss application. synthesis of polylactic acid-glycolate grafted hyaluronic acid (HA-PLGA) (E-i)[100]; the cumulative release curve (MXD solution (●), PLGA/MXD-NP (■), the HA-PLGA/MXD-NP (▲)) (E-ii)