3D-printed silicate porous bioceramics promoted the polarization of M2-macrophages that enhanced the angiogenesis in bone regeneration.

The failure of bone regeneration has been considered as a serious problem that troubling patients for decades, most of which was resulted by the poor angiogenesis and chronic inflammation after surgery. Among multiple materials applied in the repair of bone defect, silicate bioceramics attracted researchers because of its excellent bioactivity. The purpose of this study was to detect the effect of specific bioactive glass ceramic (AP40, based on crystalline phases of apatite and wollastonite) on angiogenesis and the subsequent bone growth through the modulation of macrophages. Two groups were included in this study: control group (macrophages without any stimulation, denominated as Control) and AP40 group (macrophages incubated on AP40). This study investigated the effect of AP40 on macrophages polarization (RAW264.7) and angiogenesis in vitro and in vivo. Additionally, the changes of angiogenic ability regulated by macrophages were explored. AP40 showed excellent angiogenesis potential and the expression of CD31 was promoted through the modulation of macrophages toward M2 subtype. Additionally, the macrophages incubated on AP40 synthesized more PDGF-BB comparing to macrophages without any stimulation, which contributed to the improved angiogenetic ability of human umbilical vein endothelial cells (HUVECs). Results of in vivo studies indicated increased bone ingrowth along the implants, which indicated the potential of bioceramics for bone defect repair clinically.

Clinical outcomes of a novel porcine small intestinal submucosa patch for full-thickness hand skin defects: a retrospective investigation.

OBJECTIVE: To investigate the clinical outcomes of a novel soft tissue repair patch (porcine small intestinal submucosa patch, SIS patch) in the treatment of full-thickness hand skin defects. METHODS: From January 2017 to July 2019, 80 patients with hand soft tissue defects, who met the inclusion criteria, were retrospectively reviewed and divided into two groups. After debridement, patients in group A were treated with the novel SIS patch to cover the wound, and patients in group B were treated with autologous skin graft. The dimensions of skin defect area and healing outcome were evaluated and recorded. Scar assessment was carried out using Scar Cosmesis Assessment and Rating Scale (SCAR scale) at the last follow-up postoperation, and the recovery of wound sensation was assessed at the same time using British Medical Research Council (BMRC) grading of sensorimotor recovery. All the data were collected and statistically analyzed. RESULTS: A total of 80 patients were enrolled in the study with 40 patients in each group. Four patients in group A and 5 patients in group B were excluded due to wound infection and lost to follow-up. There were 36 patients in group A and 35 patients in group B finally got follow-up postoperation with mean interval of 12.75 ± 5.61 months in group A and 14.11 ± 5.42 months in group B. The dimensions of skin defect area in group A ranged from 7.5 to 87.5 cm2 (mean 25.97 ± 18.66 cm2) and in group B ranged from 7.5 to 86.25 cm2 (mean 33.61 ± 19.27 cm2) which have no significant difference (P > 0.05). SCAR scale results of group A and group B were 10.98 ± 0.33 and 9.49 ± 0.35, respectively, and the difference was statistically significant (P < 0.05). BMRC grading results showed 6 cases of S4, 11 cases of S3+, 5 cases of S3, 6 cases of S2, 6 cases of S1 and 2 cases of S0 in group A, and 8 cases of S4, 10 cases of S3+, 7 cases of S3, 4 cases of S2, 5 cases of S1, and 1 case of S0 in group B, which had no significant difference between them (P > 0.05). CONCLUSIONS: The novel SIS patch is an applicable biological material in the treatment of hand skin defect, which could achieve a better cosmetic appearance of the newborn skin tissue.

3D Printing Technology in Planning Thumb Reconstructions with Second Toe Transplant.

OBJECTIVE: To report preoperative planning using 3D printing to plan thumb reconstructions with second toe transplant. METHODS: Between December 2013 and October 2015, the thumbs of five patients with grade 3 thumb defects were reconstructed using a wrap-around flap and second toe transplant aided by 3D printing technology. CT scans of hands and feet were analyzed using Boholo surgical simulator software (www.boholo.com). This allowed for the creation of a mirror image of the healthy thumb using the uninjured thumb. Using 3D images of the reconstructed thumb, a model of the big toe and the second toe was created to understand the dimensions of the donor site. This model was also used to repair the donor site defect by designing appropriate iliac bone and superficial circumflex iliac artery flaps. The polylactic acid model of the donor toes and reconstructed thumb was produced using 3D printing. Surgically, the wrap-around flap of the first dorsal metatarsal artery and vein combined with the joint and bone of the second toe was based upon the model donor site. Sensation was reconstructed by anastomosing the dorsal nerve of the foot and the plantar digital nerve of the great toe. Patients commenced exercises 2 weeks after surgery. RESULTS: All reconstructed thumbs survived, although partial flap necrosis occurred in one case. This was managed with regular dressing changes. Patients were followed up for 3-15 months. The lengths of the reconstructed thumbs are 34-49 mm. The widths of the thumb nail beds are 16-19 mm, and the thickness of the digital pulp is 16-20 mm. The thumb opposition function was 0-1.5 cm; the extension angle was 5°-20° (mean, 16°), and the angle of flexion was 38°-55° (mean, 47°). Two-point discrimination was 9-11 mm (mean, 9.6 mm). The reconstructed thumbs had good appearance, function and sensation. Based on the criteria set forth by the Standard on Approval of Reconstructed Thumb and Finger Functional Assessment of the Chinese Medical Association, the results were considered excellent for four cases and good for one case. The success rate was 100%. CONCLUSIONS: When planning a wrap-around flap and second toe transplant to reconstruct a thumb, both the donor and recipient sites can be modeled using 3D printing. This can shorten the operative time by supplying digital and accurate schematics for the operation. It can also optimize the function and appearance of the reconstructed thumb while minimizing damage to the donor site.

PKC-NF-κB are involved in CCL2-induced Nav1.8 expression and channel function in dorsal root ganglion neurons.

CCL2 [chemokine (C-C motif) ligand 2] contributes to the inflammation-induced neuropathic pain through activating VGSC (voltage-gated sodium channel)-mediated nerve impulse conduction, but the underlying mechanism is currently unknown. Our study aimed to investigate whether PKC (protein kinase C)-NF-κB (nuclear factor κB) is involved in CCL2-induced regulation of voltage-gated sodium Nav1.8 currents and expression. DRG (dorsal root ganglion) neurons were prepared from adult male Sprague-Dawley rats and incubated with various concentration of CCL2 for 24 h. Whole-cell patch-clamps were performed to record the Nav1.8 currents in response to the induction by CCL2. After being pretreated with 5 and10 nM CCL2 for 16 h, CCR2 [chemokine (C-C motif) receptor 2] and Nav1.8 expression significantly increased and the peak currents of Nav1.8 elevated from the baseline 46.53±4.53 pA/pF to 64.28±3.12 pA/pF following 10 nM CCL2 (P<0.05). Compared with the control, significant change in Nav1.8 current density was observed when the CCR2 inhibitor INCB3344 (10 nM) was applied. Furthermore, inhibition of PKC by AEB071 significantly eliminated CCL2-induced elevated Nav1.8 currents. In vitro PKC kinase assays and autoradiograms suggested that Nav1.8 within DRG neurons was a substrate of PKC and direct phosphorylation of the Nav1.8 channel by PKC regulates its function in these neurons. Moreover, p65 expression was significantly higher in CCL2-induced neurons (P<0.05), and was reversed by treatment with INCB3344 and AEB071. PKC-NF-κB are involved in CCL2-induced elevation of Nav1.8 current density by promoting the phosphorylation of Nav1.8 and its expression.