In vivo trial of bioresorbable mesh cages contained bone graft granules in rabbit femoral bone defects.

Bone graft granules implanted in bone defects come into physical contact with the host bone and form interconnected porous structure. However, there exists an accidental displacement of granules to unintended locations and leakage of granules from bone defects. Although covering the defect with a barrier membrane prevents granule emanation, this procedure is troublesome. To resolve these problems, we fabricated bioresorbable mesh cages (BRMc) in this study. Bone graft granules composed of carbonate apatite alone (Gr) and bioresorbable mesh cages (BRMc/Gr) introduced the bone graft granules and were implanted into the bone defect in the rabbit femur. Micro-computed tomography and histological analysis were conducted at 4 and 12 weeks after implantation. Osteoprogenitors in the bloodstream from the host bone passed through the pores of BRMc, penetrated the porous structure of graft granules, and might interact with individual granules. Then bone remodeling could progress actively and new bone was formed. The new bone formation was similar to the host bone at 12 weeks and there were minimal signs of local tissue inflammation. BRMc/Gr could reduce the risk of unwanted new bone formation occurring due to loss of granules from the bone defects compared with Gr because BRMc enclosed granules and prevent granules leakage from bone defects and BRMc could not induce unfavorable effects to forme new bone. Additionally, BRMc/Gr could keep granules assembled in one place, avoid displacement of granules to unintended locations, and carry easily. These results demonstrated that BRMc/Gr was effective in bone regeneration and improved clinical handling.

Antibacterial and osteogenic thin films on Ti-6Al-4V surface formed by passivation process in copper hydroxide solution.

Implant-associated infections are threatening and devastating complications that lead to bone destruction and loss. As a smooth surface is suitable for inhibiting bacterial adhesion, endowing antibacterial activity to the Ti surface without any structural changes in the surface topography is an effective strategy for preventing infection. The thin film on the Ti-6Al-4 V surface was functionalized to endow antibacterial activity by immersion in a Cu(OH)2 solution. The resulting surface maintains the surface topography with a surface roughness of 0.03 µm even after the immersion in the Cu(OH)2 solution. Moreover, Cu was detected at approximately 10 atom% from the surface and was present up to a depth of 30 nm of thin film. In vitro experiments revealed that the resulting surface exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus and allowed the cellular proliferation, differentiation, and calcification of MC3T3-E1 cells. Furthermore, in vivo experiments determined that the presence of Cu in the thin film on the Ti-6Al-4 V surface led to no inflammatory reactions, including bone resorption. Thus, immersion in a Cu(OH)2 solution incorporates and immobilizes Cu into the thin film on the Ti-6Al-4 V surface without any structural alternations in the surface topography, and the resulting smooth surface exhibits antibacterial activity and osteogenic cell compatibility without cytotoxicity or inflammatory reactions. Our findings provide fundamental insights into the surface design of Ti-based medical devices, to achieve bone reconstruction and infection prevention.

Passivation of Ti-6Al-4V in Cu(OH)2 solution endowed smooth thin film with antibacterial activity and osteogenic cell compatibility for potentially achieving both bone reconstruction and infection prevention.

Transformable Carbonate Apatite Chains as a Novel Type of Bone Graft.

The aging global population is generating an ever-increasing demand for bone regeneration. Various materials, including blocks, granules, and sponges, are developed for bone regeneration. However, blocks require troublesome shaping and exhibit poor bone-defect conformities; granules migrate into the surrounding tissues during and after filling of the defect, causing handling difficulties and complications; and sponges contain polymers that are subject to religious restrictions, lack osteoconductivity, and may cause inflammation and allergies. Herein, carbonate apatite chains that overcome the limitations of conventional materials are presented. Although carbonate apatite granules migrate, causing inflammation and ectopic calcification, the chains remain in the defects without causing any complications. The chains conform to the defect shape and transform into 3D porous structures, resulting in faster bone regeneration than that observed using granules. Thus, these findings indicate that even traditional calcium phosphates materials can be converted to state-of-the-art materials via shape control.

Synergistic Effect of Nano Strontium Titanate Coating and Ultraviolet C Photofunctionalization on Osteogenic Performance and Soft Tissue Sealing of poly(ether-ether-ketone).

This study aimed to evaluate the bioactivity of poly(ether ether ketone) (PEEK) after surface modification by persistent photoconductive strontium titanate (SrTiO3) magnetron sputtering and ultraviolet (UV) C irradiation. According to the different modifications, the PEEK specimens were randomly divided into five groups (n = 38/group): PEEK, Sr100-PEEK, Sr200-PEEK, UV/PEEK, and UV/Sr200-PEEK. Then, the specimens of Sr100-PEEK and Sr200-PEEK groups were, respectively, coated with 100 and 200 nm thickness photocatalyst SrTiO3 on the PEEK surface by magnetron sputtering. Subsequently, UV-C light photofunctionalized the specimens of PEEK and Sr200-PEEK groups to form UV/PEEK and UV/Sr200-PEEK groups. The specimens were characterized by a step meter, scanning electron microscopy (SEM), atomic force microscopy (AFM), energy dispersive X-ray spectroscopy (EDX), and a water contact angle meter. The release test of the Sr ion was performed by inductively coupled plasma mass spectrometry (ICP-MS). In vitro study, osteogenic activity (MC3T3-E1 osteoblast-like cells) and epithelial and connective tissue attachment (gingival epithelial cells GE1 and fibroblasts NIH3T3) were analyzed in five groups. Surface morphology of the specimens was changed after coating, and the Sr content on the Sr-PEEK surface was increased with increasing coating thickness. In addition, the contact angle was increased significantly after magnetron sputtering. After UV-C photofunctionalization, the content of surface elements changed and the contact angle was decreased. The release of Sr ion was sustained, and the final cumulative release amount did not exceed the safety limit. In vitro experiments showed that SrTiO3 improved the cell activity of MC3T3-E1 and UV-C irradiation further enhanced the osteogenic performance of PEEK. Besides, UV-C irradiation also significantly promoted the cell viability, development, and expression of adhesion proteins of GE1 and NIH3T3 on PEEK. The present investigation demonstrated that nano SrTiO3 coating with UV-C photofunctionalization synergistically enhanced the osteogenic properties and soft tissue sealing function of PEEK in vitro.

Releasable, Immune-Instructive, Bioinspired Multilayer Coating Resists Implant-Induced Fibrosis while Accelerating Tissue Repair.

Implantable biomaterials trigger foreign body reactions (FBRs), which reduces the functional life of medical devices and prevents effective tissue regeneration. Although existing therapeutic approaches can circumvent collagen-rich fibrotic encapsulation secondary to FBRs, they disrupt native tissue repair. Herein, a new surface engineering strategy in which an apoptotic-mimetic, immunomodulatory, phosphatidylserine liposome (PSL) is released from an implant coating to induce the formation of a macrophage phenotype that mitigates FBRs and improves tissue healing is described. PSL-multilayers constructed on implant surfaces via the layer-by-layer method release PSLs over a 1-month period. In rat muscles, poly(etheretherketone) (PEEK), a nondegradable polymer implant model, induces FBRs with dense fibrotic scarring under an aberrant cellular profile that recruits high levels of inflammatory infiltrates, foreign body giant cells (FBGCs), scar-forming myofibroblasts, and inflammatory M1-like macrophages but negligible amounts of anti-inflammatory M2-like phenotypes. However, the PSL-multilayer coating markedly diminishes these detrimental signatures by shifting the macrophage phenotype. Unlike other therapeutics, PSL-multilayered coatings also stimulate muscle regeneration. This study demonstrates that PSL-multilayered coatings are effective in eliminating FBRs and promoting regeneration, hence offering potent and broad applications for implantable biomaterials.

Effects of Space Dimensionality within Scaffold for Bone Regeneration with Large and Oriented Blood Vessels.

The internal structure of the scaffolds is a key factor for bone regeneration. In this study, we focused on the space dimensionality within the scaffold that may control cell migration and evaluated the effects on the size and orientation of blood vessels and the amount of bone formation in the scaffold. The carbonate apatite scaffolds with intrascaffold space allowing one-dimensional (1D), two-dimensional (2D), or three-dimensional (3D) cell migration were fabricated by 3D printing. These scaffolds had the same space size, i.e., distances between the struts (~300 µm). The scaffolds were implanted into the medial condyle of rabbit femurs for four weeks. Both the size and orientation degree of the blood vessels formed in the scaffolds allowing 1D cell migration were 2.5- to 4.0-fold greater than those of the blood vessels formed in the scaffolds allowing 2D and 3D cell migration. Furthermore, the amount of bone formed in the scaffolds allowing 1D cell migration was 1.4-fold larger than that formed in the scaffolds allowing 2D and 3D cell migration. These are probably because the 1D space limited the direction of cell migration and prevented the branching of blood vessels, whereas 2D and 3D spaces provided the opportunity for random cell migration and blood vessel branching. Thus, scaffolds with 1D space are advantageous for inducing large and oriented blood vessels, resulting in a larger amount of bone formation.

Obvious advantage of vaginal natural orifice transluminal endoscopic surgery hysterectomy against total laparoscopic hysterectomy in small uterus patients and the future prospects at a regional core institution: A retrospective study.

Objective: Owing to the combination of benefits, including permanent visual guidance and no abdominal skin incision, vaginal natural orifice transluminal endoscopic surgery hysterectomy (vNOTES-H) is currently widely used. However, the introduction of vNOTES-H has been delayed in many Japanese regional core hospitals because of its specific device and skill requirements. Therefore, the characteristics and advantages should be explained for the widespread use of this technique. Study design: We reviewed the medical records of 17 patients with vNOTES-H and 94 patients with total laparoscopic hysterectomy (TLH) from January 1, 2015 to December 31, 2022. In this analysis, to compare the results of vNOTES-H to TLH, we excluded certain patients with a relatively heavy uterus (>255 g) and the presence of abdominal adhesions. In this report, first, the characteristics of the vNOTES-H procedures using a transvaginal access platform are explained by referring to one representative patient. Second, the patient characteristics of the vNOTES-H and TLH groups, including operation time and blood loss amount, were compared. Then, to detect the influence of vNOTES-H on the difficulty of operation among all 111 patients, we performed a multivariate logistic regression analysis to assess the influence of each of 9 factors, including "vNOTES-H", "Advanced age", "High BMI", "3 parity", "Gynaecological operation history", "Adenomyoma", "Large leiomyoma", "Heavy uterus" and "Large uterus", on the two indexes, including "Short time operation" and "Massive blood loss". Results: In the simple comparison between the groups with vNOTES-H and TLH, the operation time in the former group was significantly shorter than in the latter group, although other factors did not show significant differences, including blood loss amount. Moreover, in the multivariate logistic regression analysis of all 111 patients, the "vNOTES-H" factor showed a significantly high possibility of "short time operation", although no factor, including "vNOTES-H", showed a significant influence on "massive blood loss". Conclusions: vNOTES-H showed advantages in terms of operation time without increasing blood loss for patients with a relatively small uterus. However, to expand the selection for vNOTES-H, we should accumulate further patients and perform more analyses.

Superiority of Triply Periodic Minimal Surface Gyroid Structure to Strut-Based Grid Structure in Both Strength and Bone Regeneration.

The aging population has rapidly driven the demand for bone regeneration. The pore structure of a scaffold is a critical factor that affects its mechanical strength and bone regeneration. Triply periodic minimal surface gyroid structures similar to the trabecular bone structure are considered superior to strut-based lattice structures (e.g., grids) in terms of bone regeneration. However, at this stage, this is only a hypothesis and is not supported by evidence. In this study, we experimentally validated this hypothesis by comparing gyroid and grid scaffolds composed of carbonate apatite. The gyroid scaffolds possessed compressive strength approximately 1.6-fold higher than that of the grid scaffolds because the gyroid structure prevented stress concentration, whereas the grid structure could not. The porosity of gyroid scaffolds was higher than that of the grid scaffolds; however, porosity and compressive strength generally have a trade-off relationship. Moreover, the gyroid scaffolds formed more than twice the amount of bone as grid scaffolds in a critical-sized bone defect in rabbit femur condyles. This favorable bone regeneration using gyroid scaffolds was attributed to the high permeability (i.e., larger volume of macropores or porosity) and curvature profile of the gyroid structure. Thus, this study validated the conventional hypothesis using in vivo experiments and revealed factors that led to this hypothetical outcome. The findings of this study are expected to contribute to the development of scaffolds that can achieve early bone regeneration without sacrificing the mechanical strength.

Desmoid Tumor Mimicking Port Site Metastasis after Laparoscopic Surgery for Endometrial Cancer.

Desmoid tumors are rare; however, they sometimes form in the abdominal wall after surgery or trauma. We report a case of desmoid tumors in the abdominal wall mimicking port-site metastasis after laparoscopic surgery for endometrial cancer. A 53-year-old woman with familial adenomatous polyposis presented to our hospital with vaginal bleeding and was diagnosed with endometrial cancer. We performed a total laparoscopic hysterectomy and began observation. Two years after surgery, follow-up computed tomography revealed three nodules with a size of approximately 15 mm in the abdominal wall at the trocar sites. Tumorectomy was performed because endometrial cancer recurrence was suspected, but desmoid fibromatosis was finally diagnosed. This is the first report of desmoid tumors at the trocar site after laparoscopic surgery for uterine endometrial cancer. Gynecologists should be aware of this disease because differentiating it from metastatic recurrence is challenging.

Comparison of robotic-assisted laparoscopic hysterectomy to total laparoscopic hysterectomy in terms of operational complications at a regional institution: A retrospective study.

Objective: With the increased use of total laparoscopic hysterectomy (TLH), the use of robotic-assisted laparoscopic hysterectomy (RALH) has increased due to its technical advantages. On the other hand, RALH has some disadvantages, including its high cost, which includes not only the purchase price of robotic technology systems but also the running cost and long preparation time for setting assistant robots. Therefore, an overall understanding of the characteristics of RALH is needed. Study design: We reviewed the medical records of 432 patients with TLH and 93 patients with RALH from January 1, 2015, to December 31, 2022. In this analysis, we excluded certain cases with concomitant laparoscopic cystectomy (LC) and a heavy uterus (> 400 g). First, the patient characteristics of the TLH and RALH groups, including operation time and blood loss amount, were compared. Then, among these cases, we sought to predict difficult cases for TLH and RALH by identifying risk factors related to each of the following three categories of operational complications: "long operation time", "massive blood loss" and "other complications". For this purpose, multivariate logistic regression analyses were performed to assess the influence of each of 7 representative factors, namely, "advanced age", "high body mass index (BMI)", "nulliparity", "concomitant pelvic lymphadenectomy (PLA)", "heavy uterus", "abdominal adhesion", and "large leiomyoma". Results: In the simple comparison without various factors, there was an advantage of RALH in both the average operation time and blood loss amount. However, in the multivariate logistic regression analyses, a significant risk was detected in the following relationships: 1) between "long-term operation" and "abdominal adhesion" and 2) between "other complications" and "heavy uterus". Conclusions: RALH has sufficient advantages over TLH regarding at least in terms of blood loss amount; however, since RALH may have potential weaknesses in the context of complex cases, additional cases and analyses are needed.

Gear-shaped carbonate apatite granules with a hexagonal macropore for rapid bone regeneration.

Synthetic bone grafts are in high demand owing to increased age-related bone disorders in the global aging population. Here, we report fabrication of gear-shaped granules (G-GRNs) for rapid bone healing. G-GRNs possessed six protrusions and a hexagonal macropore in the granular center. These were composed of carbonate apatite, i.e., bone mineral, microspheres with ∼1-µm micropores in the spaces between the microspheres. G-GRNs formed new bone and blood vessels (both on the granular surface and within the macropores) 4 weeks after implantation in the rabbit femur defects. The formed bone structure was similar to that of cancellous bone. The bone percentage in the defect recovered to that in a normal rabbit femur at week-4 post-implantation, and the bone percentage remained constant for the following 8 weeks. Throughout the entire period, the bone percentage in the G-GRN-implanted group was ∼10% higher than that of the group implanted with conventional carbonate apatite granules. Furthermore, a portion of the G-GRNs resorbed at week-4, and resorption continued for the following 8 weeks. Thus, G-GRNs are involved in bone remodeling and are gradually replaced with new bone while maintaining a suitable bone level. These findings provide a basis for the design and fabrication of synthetic bone grafts for achieving rapid bone regeneration.

Preventive effect of metronidazole vaginal tablets on vaginal bacteria-related postoperative complications with total laparoscopic hysterectomy.

BACKGROUND: The use of total laparoscopic hysterectomy is increasing. However, as with conventional abdominal hysterectomy, vaginal bacteria-related postoperative complications need to be managed in total laparoscopic hysterectomy. Therefore, we started to combine metronidazole vaginal tablets with intravenous administration of cephem antibiotics immediately before starting surgery to reduce complications. To evaluate the effect of this combination, and to determine the risk factors for these complications, we retrospectively collected medical records from our hospital and performed a multivariate analysis. METHODS: We reviewed the medical records of 520 patients who underwent total laparoscopic hysterectomy from 1 January 2015 to 31 December 2021. Among these cases, we identified 16 cases as having vaginal bacteria-related postoperative complications, defined as needing more than one additional day for treatment of postoperative complications, namely postoperative infection (10 cases) and vaginal dehiscence (6 cases). First, we evaluate the effect of metronidazole vaginal tablets by dividing the patients into two groups according to whether metronidazole vaginal tablets were used, and comparing the vaginal bacteria-related postoperative complication rates and other indices. Second, we performed a multivariate logistic regression analysis to assess the influence of each of 17 representative factors, including patient characteristics and symptoms, uterus and leiomyoma sizes, concomitant procedures such as laparoscopic cystectomy and pelvic lymphadenectomy, and others. RESULTS: In the multivariate analysis of the 520 cases, we confirmed that the use of metronidazole vaginal tablets could reduce the vaginal bacteria-related postoperative complications rate by more than half (odds ratio, 0.36). In addition to metronidazole vaginal tablets use, concomitant laparoscopic cystectomy and blood transfusion were associated with significant increases in the vaginal bacteria-related postoperative complication rate. CONCLUSIONS: The effect of the addition of metronidazole vaginal tablets to pre- and postsurgical treatment on the reduction of vaginal bacteria-related postoperative complications was confirmed. This easy, safe, and low-cost method may improve the management of total laparoscopic hysterectomy.

Current surface modification strategies to improve the binding efficiency of emerging biomaterial polyetheretherketone (PEEK) with bone and soft tissue: A literature review.

PURPOSE: The aim of this study was to review the literature on current surface modification strategies used to improve the binding efficiency of an emerging biological material, polyetheretherketone (PEEK), with bone and soft tissues. STUDY SELECTION: This review was based on articles retrieved from PubMed, Google Scholar, Web of Science, and ScienceDirect databases. The main keywords used during the search were "polyetheretherketone (PEEK)," "implant," "surface modification," "biomaterials," "bone," "osseointegration," and "soft tissue." RESULTS: The suitability of PEEK surface modification strategies has been critically analyzed and summarized here. Many cell and in vivo experiments in small animals have shown that the use of advanced modification technologies with appropriate surface modification strategies can effectively improve the surface inertness of PEEK, thereby improving its binding efficiency with bone and soft tissues. CONCLUSIONS: Surface modifications of PEEK have revealed new possibilities for implant treatment; however, most results are based on in vitro or short-term in vivo evaluations in small animals. To achieve a broad application of PEEK in the field of oral implantology, more in vivo experiments and long-term clinical evaluations are needed to investigate the effects of various surface modifications on the tissue integration ability of PEEK to develop an ideal implant material.

Structurally optimized honeycomb scaffolds with outstanding ability for vertical bone augmentation.

INTRODUCTION: Cases of intractable dental implant require vertical bone augmentation; however, the predicted bone height and volume are difficult to obtain. In vertical bone augmentation, the contact surface between the scaffold and the bone is limited to the bottom face of the scaffold. Furthermore, the strength decrease caused by scaffold resorption leads to collapse of the augmented site, leading to a decrease in the bone volume and height. OBJECTIVES: To promote bone ingrowth, we fabricated carbonate apatite (i.e., bone mineral) honeycomb (HC) scaffolds with uniaxial channels vertically penetrating the scaffold. Furthermore, we controlled the scaffold resorption rate, eventually the endurability for compression, and the bone height and volume by controlling the strut thickness. METHODS: The channel aperture was controlled to be 230-260 µm to promote bone ingrowth. Furthermore, the strut thicknesses of the HC scaffolds were adjusted to 100, 200, and 300 µm to control the scaffold resorption; these scaffolds were designated as HC100, HC200, and HC300, respectively. RESULTS: At 4 weeks post-implantation on rabbit calvarium, all scaffolds had already vertically augmented new bone close to the top surface of the scaffold. In the following 8 weeks, the height and amount of new bone in all scaffolds increased. Notably, HC300 was resorbed synchronously with new bone formation, allowing it to endure the compression from the fasciae for 12 weeks post-implantation. Furthermore, HC300 formed larger-diameter blood vessels than those of HC100 and HC200. CONCLUSION: The HC scaffolds surpassed the various combined scaffolds and growth factors or stem cells in the ability for vertical bone augmentation. Thus, the HC structure is inherently suitable for vertical bone augmentation. Notably, the HC scaffolds with 300-µm-thick struts enhanced both new bone formation and angiogenesis. This study revealed a structurally suitable design for achieving an outstanding outcome in vertical bone augmentation.

Channel Aperture Characteristics of Carbonate Apatite Honeycomb Scaffolds Affect Ingrowths of Bone and Fibrous Tissues in Vertical Bone Augmentation.

Synthetic scaffolds with the ability to prevent fibrous tissue penetration and promote bone augmentation may realize guided bone regeneration without the use of a barrier membrane for dental implantation. Here, we fabricated two types of honeycomb scaffolds of carbonate apatite, a bone mineral analog, whose channel apertures were square (HC-S) and rectangular (HC-R). The side lengths of the HC-Ss and HC-Rs were 265.8 ± 8.9; 817.7 ± 2.4 and 267.1 ± 5.2 µm, respectively. We placed cylindrical HC-Ss and HC-Rs on the rabbit calvaria. At 4 weeks post-implantation, the HC-Ss prevented fibrous tissue penetration from the top face via the channels, which allowed the new bone to reach the top of the scaffold from the bottom face or the calvarium. In contrast, in the HC-Rs, fibrous tissues filled the channels in the top region. At 12 weeks post-implantation, the HC-Ss were partially replaced with new bone. In the top region of the HC-Rs, although new bone had formed, fibrous tissue remained. According to the findings here and in our previous study, the longer side length rather than the shorter side length of a rectangular scaffold channel aperture is the dominant factor that affects fibrous tissue penetration and new bone augmentation. Furthermore, even though channel aperture areas are similar, bone and fibrous tissue ingrowths are different when the aperture shapes are different.

Phosphatidylserine liposome multilayers mediate the M1-to-M2 macrophage polarization to enhance bone tissue regeneration.

An appropriate immune microenvironment, governed by macrophages, is essential for rapid tissue regeneration after biomaterial implantation. The macrophage phenotypes, M1 (inflammatory) and M2 (anti-inflammatory/healing), exert opposing effects on the repair of various tissues. In this study, a new strategy to promote tissue repair and tissue-to-biomaterial integration by M1-to-M2 macrophage transition using artificial apoptotic cell mimetics (phosphatidylserine liposomes; PSLs) was developed using bone as a model tissue. Titanium was also selected as a model substrate material because it is widely used for dental and orthopedic implants. Titanium implants were functionalized with multilayers via layer-by-layer assembly of cationic protamine and negatively charged PSLs that were chemically stabilized to prevent disruption of lipid bilayers. Samples carrying PSL multilayers could drive M1-type macrophages into M2-biased phenotypes, resulting in a dramatic change in macrophage secretion for tissue regeneration. In a rat femur implantation model, the PSL-multilayer-coated implant displayed augmented de novo bone formation and bone-to-implant integration, associated with an increased M1-to-M2-like phenotypic transition. This triggered the proper generation and activation of bone-forming osteoblasts and bone-resorbing osteoclasts relative to their uncoated counterparts. This study demonstrates the benefit of local M1-to-M2 macrophage polarization induced by PSL-multilayers constructed on implants for potent bone regeneration and bone-to-implant integration. The results of this study may help in the design of new immunomodulatory biomaterials. STATEMENT OF SIGNIFICANCE: Effective strategies for tissue regeneration are essential in the clinical practice. The macrophage phenotypes, M1 (inflammatory) and M2 (anti-inflammatory/healing), exert opposing effects on the repair of various tissues. Artificially produced phosphatidylserine-containing liposomes (PSLs) can induce M2 macrophage polarization by mimicking the inverted plasma membranes of apoptotic cells. This study demonstrates the advantages of local M1-to-M2 macrophage polarization induced by PSL-multilayers constructed on implants for effective bone regeneration and osseointegration (bone-to-implant integration). Mechanistically, M2 macrophages promote osteogenesis but inhibit osteoclastogenesis, and M1 macrophages vice versa. We believe that our study makes a significant contribution to the design of new immunomodulatory biomaterials for regenerative medicine because it is the first to validate the benefit of PSLs for tissue regeneration.

Surface functionalization with copper endows carbonate apatite honeycomb scaffold with antibacterial, proangiogenic, and pro-osteogenic activities.

Osteomyelitis is a potentially devastating inflammatory bone disease that leads to bone destruction and loss. Treatment of osteomyelitis requires the removal of residual bacteria as well as osteogenesis with angiogenesis at the site of treatment. Use of an appropriate amount of copper (Cu) in treatment scaffolds may achieve these goals without the risk of toxicity. In this study, the surface of the carbonate apatite honeycomb scaffold was functionalized with Cu through a dissolution-precipitation reaction. The resulting scaffolds retained the honeycomb structure after immersion in CuCl2 solution, and Cu was precipitated on the surface as libethenite [Cu2(OH)PO4]. The surface Cu concentration was controlled by the concentration of the CuCl2 solution. Scaffolds with a surface Cu concentration of 23.8 wt% exhibited antibacterial and cytotoxic effects, whereas those with concentrations of ≤4.6 wt% exerted antibacterial effects without negatively affecting the cellular adhesion, proliferation, differentiation, and calcification of osteoblast-like cells. Furthermore, scaffolds with a surface Cu concentration of 4.6 wt% Cu inhibited bacterial growth for at least 28 days and displayed proangiogenic and pro-osteogenic activities in vivo. These data confirm the success in functionalizing scaffolds with Cu that may be utilized as an innovative osteomyelitis therapy.

The effect of temporary uterine artery ligation on laparoscopic myomectomy to reduce intraoperative blood loss: A retrospective case-control study.

Objective: To reduce intraoperative blood loss in laparoscopic myomectomy, uterine artery occlusion or temporary uterine artery clipping have been employed. Recently, in addition to these techniques, temporary uterine artery ligation has been reported as a new method that has less invasive effects on fertility and needs no special devices to be used. This study aimed to evaluate the effect of temporary uterine artery ligation to minimize intraoperative blood loss during laparoscopic myomectomy. Study Design: This was a retrospective case-control study at the department of Obstetrics and Gynaecology, University Hospital Mizonokuchi, Teikyo University School of Medicine. A total of 264 patients with uterine leiomyoma who underwent laparoscopic myomectomy were enrolled in this study. We divided the patients into two groups, those who underwent temporary uterine artery ligation (52 patients) and those who did not (212 patients) and compared the operation time, blood loss volume, and other indexes. Second, to identify influential factors, we assessed the effects of 11 representative factors on massive blood loss or a prolonged operation time using multivariate analysis. Results: The intraoperative blood loss volume was decreased by approximately half with the addition of temporary uterine artery ligation (75.1 ± 73.6 ml vs. 158.5 ± 233.2 ml, p = 0.011), but the operation time was longer (200.5 ± 46.9 min vs. 160.1 ± 51.3 min, p < 0.001). Among the 264 patients, 25 patients (9/52 in the case group and 16/212 in the control group) had a prolonged operation time (≥ 240 min), and 24 patients (1/52 in the case group and 23/212 in the control group) experienced massive blood loss (≥ 400 ml). In the multivariate analysis, high body mass index, concomitant surgery and temporary uterine artery ligation showed a positive association with a prolonged operative time, and the presence of single leiomyoma showed a negative association. Concomitant surgery and the presence of large leiomyoma showed a positive association with massive blood loss, and temporary uterine artery ligation showed a negative association. Conclusions: By performing temporary uterine artery ligation during laparoscopic myomectomy, the volume of intraoperative blood loss could be decreased, especially in patients with large leiomyomas. However, because this procedure prolongs the operation time, there is still room for improvement.

Unilateral uterine artery embolization and Bakri tamponade balloon insertion in the treatment of acute puerperal uterine inversion: a case report.

BACKGROUND: Acute puerperal uterine inversion is rare but may cause massive postpartum blood loss due to uterine atony. Therefore, these patients must be diagnosed, and uterine replacement must be performed as soon as possible. However, in some cases, active bleeding due to uterine atony becomes uncontrollable, even though the uterine inversion itself is treated. In these cases, additional treatments, including surgical procedures, are needed. CASE PRESENTATION: A 41-year-old Japanese woman, gravida 1, para 0, was hospitalized for labor induction at 40 weeks and 3 days of gestational age. She had a vacuum-assisted delivery after 3 days of oxytocin administration, but acute uterine inversion occurred. Although replacement of the inverted uterus was successful by manual repositioning and Bakri balloon tamponade insertion, massive postpartum hemorrhage caused by uterine atony became uncontrollable. In this situation, since disseminated intravascular coagulation had developed, we used uterine artery embolization to stop the bleeding. After detecting the pseudo-aneurysmal sac and tortuous vessels of the right uterine artery, transcatheter right-sided uterine artery embolization was performed. Thirteen days after uterine artery embolization, she was discharged with no complications. CONCLUSIONS: In cases of disseminated intravascular coagulation caused by massive postpartum bleeding, uterine artery embolization may often be selected. In our case, since we performed angiography to detect the main bleeding site, the hemorrhage could be stopped with unilateral uterine artery embolization alone, without hysterectomy.

Effects of pore interconnectivity on bone regeneration in carbonate apatite blocks.

Porous architecture in bone substitutes, notably the interconnectivity of pores, is a critical factor for bone ingrowth. However, controlling the pore interconnectivity while maintaining the microarchitecture has not yet been achieved using conventional methods, such as sintering. Herein, we fabricated a porous block using the crystal growth of calcium sulfate dihydrate, and controlled the pore interconnectivity by limiting the region of crystal growth. The calcium sulfate dihydrate blocks were transformed to bone apatite, carbonate apatite (CO3Ap) through dissolution-precipitation reactions. Thus, CO3Ap blocks with 15% and 30% interconnected pore volumes were obtained while maintaining the microarchitecture: they were designated as CO3Ap-15 and CO3Ap-30, respectively. At 4 weeks after implantation in a rabbit femur defect, new bone formed throughout CO3Ap-30, whereas little bone was formed in the center region of CO3Ap-15. At 12 weeks after implantation, a large portion of CO3Ap-30 was replaced with new bone and the boundary with the host bone became blurred. In contrast, CO3Ap-15 remained in the defect and the boundary with the host bone was still clear. Thus, the interconnected pores promote bone ingrowth, followed by replacement of the material with new bone. These findings provide a useful guide for designing bone substitutes for rapid bone regeneration.