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.

Generation of biohybrid implants using a multipotent human periodontal ligament cell line and bioactive core materials.

We aimed to generate periodontal ligament (PDL) tissue-like structures from a multipotent human PDL cell line using three-dimensional (3D) bioprinting technology and to incorporate these structures with bioactive core materials to develop a new biohybrid implant system. After 3D bioprinting, single-cell spheroids were able to form 3D tubular structures (3DTBs). We established three types of complexes using 3DTBs and different core materials: 3DTB-titanium core (TIC), 3DTB-hydroxyapatite core (HAC), and 3DTB without a core material (WOC). The expressions of PDL-, angiogenesis-, cementum-, and bone-related genes were significantly increased in the three complexes compared with monolayer-cultured cells. Abundant collagen fibers and cells positive for the above markers were confirmed in the three complexes. However, more positive cells were detected in HAC than in WOC or TIC. The present results suggest that 3D-bioprinted structures and hydroxyapatite core materials can function similarly to the PDL and may be useful for the development of a new biohybrid implant system.

Safety and efficacy of etelcalcetide, an intravenous calcimimetic, for up to 52 weeks in hemodialysis patients with secondary hyperparathyroidism: results of a post-marketing surveillance in Japan.

BACKGROUND: Etelcalcetide is a second-generation calcimimetic for the management of secondary hyperparathyroidism (SHPT) in patients on dialysis. We performed a post-marketing surveillance (PMS) to obtain information on the safety and efficacy of etelcalcetide in clinical practice in Japan. METHODS: This PMS enrolled SHPT patients who started initial treatment with etelcalcetide between April 1, 2017 and February 28, 2018 in Japan. Safety [adverse drug reactions (ADRs)] and efficacy [serum intact parathyroid hormone (iPTH), corrected calcium (cCa), phosphorous (P), and alkaline phosphatase (ALP)] were recorded for up to 52 weeks or until treatment discontinuation. Treatment decisions were at the physician's discretion. RESULTS: Of 1226 patients enrolled across 282 centers, safety and efficacy data were available for 1195 and 1192, respectively, while 933 continued treatment to Week 52. The starting dose was 5 mg in 82.0% of patients. There were 218 ADRs in 169 patients (14.1%). Metabolism and nutrition disorders (8.8%), adverse laboratory test results (1.8%), and gastrointestinal disorders (1.6%) were the most frequent classes of ADRs. Hypocalcemia-related ADRs occurred in 104 patients (8.7%). The percentage of patients with iPTH levels within the target range (60-240 pg/mL) steadily increased from 19.5% at Week 0 to 64.1% at Week 52 or last dose. cCa, P, and ALP levels remained well controlled. CONCLUSION: This was the first real-world, large-scale, long-term observational PMS of etelcalcetide in Japan. We did not observe any new safety concerns. Etelcalcetide was associated with clinically relevant improvements in serum iPTH and maintenance of serum cCa, P, and ALP levels.

[Significance of Transitions in Neutrophil-to-Lymphocyte Ratio before and after Transcatheter Arterial Chemoembolizaton for Hepatocellular Carcinoma].

We investigated the significance of transitions in the neutrophil-to-lymphocyte ratio(NLR)before and after TACE for HCC could be a predictor of prognosis. The subjects were 108 patients with the first TACE performed from January 2010 to December 2019. NLR was calculated before and 1 month after TACE, and the relationship with therapeutic effect and prognosis was examined. When the transition of NLR before and after TACE was classified into 3 groups with a cut-off value of 5.0, group A(less than 5.0 after TACE): 52 cases(48.1%), group B(5.0 or more after TACE): 33 cases(30.6%)and C group(5.0 or more before and after TACE): 23 cases(21.3%). Median survival time were 25.0 months in group A, 18.5 months in group B, and 12.7 months in group C(p=0.0005). In multivariate analysis, treatment effect, NLR transition, AFP value, and serum albumin level were prognostic factors for HCC after TACE. Changes in NLR before and after TACE may help predict more detailed prognosis.

[Four Cases of Liver Resection for Liver Metastases from Renal Cell Carcinoma].

We report 4 cases of liver metastasis from renal cell carcinoma(RCC). Case 1: 72 years old, female. Pancreatic metastasis was resected 7 years after resection of left RCC, and hepatic posterior sectionectomy was performed for multiple liver metastases 2 years later. After that, multi-organ metastasis appeared and she died of the primary disease. Case 2: 72 years old, male. Liver metastasis and right RCC appeared 16 years after resection of left RCC, and hepatic posterior sectionectomy and partial resection of right kidney were performed. Nine months later, liver metastasis recurred and hepatic partial resection was performed. Case 3: 55 years old, male. After surgery for right RCC with tumor thrombus in the right atrium, multiple lung and liver metastases appeared, and hepatic central bisectionectomy was performed after chemotherapy. Case 4: 60 years old, male. Multiple pancreatic and lung metastases appeared 10 years after resection of left RCC, and most of them shrank or disappeared with chemotherapy. But increasing metastases appeared in the tail of pancreas and the right lobe of liver 16 months later, and hepatic subsegmentectomy and distal pancreatectomy were performed. Multidisciplinary treatment such as aggressive chemotherapy and excision is expected to improve the prognosis for liver metastasis from RCC.

[A Case of Advanced and Recurrent Colon Cancer with Long-Term Survival after Seven Repeated Surgical Resections].

We hereby report a case of advanced and recurrent colon cancer with long-term survival after 7 repeated surgical resections. A 73-year-old woman initially underwent right hemicolectomy and partial hepatectomy for an ascending colon cancer with synchronous liver metastasis. Pathological diagnosis of the tumors were moderately differentiated adenocarcinoma and metastasis to the liver compatibly. Final clinical stage was diagnosed as fT3N2M1(H1), fStage Ⅳ. But she was interrupted oxaliplatin-based adjuvant chemotherapy after 6 courses of CAPOX because of adverse drug reaction. One year after first operation, partial resection of right lung was performed for lung metastasis. Two years after first operation, 2nd resection of liver was performed for 2 liver metastatic lesions. Three years after first operation, 3rd partial liver resection, 2nd and 3rd partial lung resections were performed for metachronous metastases during 1 year. After 3 years recurrence free period, she complained of an induration of right neck and diagnosed as neck and supra clavicular lymph nodes metastases. Lymph nodes resection was performed. After the last operation, she has no sign of cancer recurrence for 1 year and 7 months, eventually she has been alive for 7 years and 7 months after the initial operation.

Enhanced Osseointegration Capability of Poly(ether ether ketone) via Combined Phosphate and Calcium Surface-Functionalization.

Biomedical applications of poly(ether ether ketone) (PEEK) are hindered by its inherent bioinertness and lack of osseointegration capability. In the present study, to enhance osteogenic activity and, hence, the osseointegration capability of PEEK, we proposed a strategy of combined phosphate and calcium surface-functionalization, in which ozone-gas treatment and wet chemistry were used for introduction of hydroxyl groups and modification of phosphate and/or calcium, respectively. Surface functionalization significantly elevated the surface hydrophilicity without changing the surface roughness or topography. The cell study demonstrated that immobilization of phosphate or calcium increased the osteogenesis of rat mesenchymal stem cells compared with bare PEEK, including cell proliferation, alkaline phosphatase activity, and bone-like nodule formation. Interestingly, further enhancement was observed for samples co-immobilized with phosphate and calcium. Furthermore, in the animal study, phosphate and calcium co-functionalized PEEK demonstrated significantly enhanced osseointegration, as revealed by a greater direct bone-to-implant contact ratio and bond strength between the bone and implant than unfunctionalized and phosphate-functionalized PEEK, which paves the way for the orthopedic and dental application of PEEK.

Predictive factors for emergent surgical intervention in patients with ovarian endometrioma hospitalized for pelvic inflammatory disease: A retrospective observational study.

AIM: The aim of this study was to identify predictive factors for emergent surgical interventions in patients with ovarian endometriomas hospitalized for pelvic inflammatory disease (PID). METHODS: We retrospectively identified 22 patients with ovarian endometriomas who were hospitalized to manage PID. Patients were divided into two groups: those who required emergent surgery after failed antibiotic therapy (emergent surgery group, n = 6) and those who were discharged with successful antibiotic therapy (conservative group, n = 16). Logistic regression analysis was performed to analyze the factors associated with emergent surgery. RESULTS: Patients in the emergent surgery group were significantly more likely to have intrauterine or intrapelvic procedures before the onset of PID compared to those in the conservative group (83% vs 38%, odds ratio 8.33, 95% confidence interval 1.02-181.3; P = 0.048). The mean interval between the onset of PID symptoms and the commencement of parenteral antibiotic therapy was significantly longer in the emergent surgery compared to the conservative group (6.5 vs 1 day, odds ratio 1.28, 95% confidence interval 1.01-1.75; P = 0.041). CONCLUSION: A history of an intrauterine or intrapelvic procedure before the onset of PID was more likely to result in emergent surgery. A longer interval between the onset of PID symptoms and the commencement of parenteral antibiotics was also associated with emergent surgery. These findings could help to identify patients with ovarian endometriomas hospitalized with PID at higher risk of emergent surgical intervention.

[Evaluation of Eligibility Criteria for Elderly Patients of Pancreaticoduodenectomy].

BACKGROUND/AIM: Pancreaticoduodenectomy(PD)treatment outcomes in elderly patients have been reported to be acceptable, but the eligibility criteria are not clear. To elucidate the importance of PD in octogenarians, we set beforehand the eligibility criteria in the elderly and evaluated whether the validity of the patient selection was adaptable. PATIENTS AND METHODS: The study population consisted of 244 patients aged >70 years who hadpancreaticobiliary cancer. The patients were divided into 2 groups as follows: 32 patients in the octogenarian group and 212 patients in the septuagenarian group. The eligibility criteria were as follows: (1)cardiac function as ejection fraction of at least 40%, measured using Doppler echocardiography; (2)pulmonary function as forcedexpiratory volume in 1 second(FEV1.0%)of at least 50%on spirography; (3) nutritional status as serum albumin level of at least 3.0 g/dL; (4)daily activity status as Karnofsky performance status of at least 80%; and(5)psychological independence status as the capability of self-determination with respect to surgery. Postoperative morbidity and long-term outcome were comparedbetween the 2 groups, andprognostic factors relating to survival time were identified. RESULTS: The patients in the octogenarian group showed a significantly higher incidence rates of 2 or more comorbidities(p<0.0001)andd elirium(p=0.024). The difference in mortality rate between the 2 groups was not significant. No significant difference in overall survival rate was found between the 2 groups(p=0.197). The independent prognostic factors relating to survival duration were intraoperative blood loss(p=0.0008)andd uration of surgery(p= 0.0091). CONCLUSION: The eligibility criteria for PD in elderly patients are also satisfactorily applicable to octogenarian patients. These criteria may be helpful when uncertainties arise regarding the selection of PD.

[A Case of Borderline Resectable Pancreatic Head Cancer Treated by Curative Resection after Chemotherapy].

A 77-year-old woman with back and epigastric pains was diagnosed with pancreatic head cancer according to the result of contrast computed tomography, which showed a 25mm irregular low-density area at the pancreatic head infiltrating nearly half of the superior mesenteric plexus. There were no findings of lymph node metastasis or distant metastasis. The pretreatment diagnosis was borderline resectable(BR)pancreatic head cancer, cT3, N0, M0, cStage ⅡA. The patient was treated with gemcitabine plus nab-paclitaxel therapy. She developed Grade 3 neutropenia, and the dose was adjusted in order to continue chemotherapy. The size of the tumor had reduced to 15mm after 6 courses of the therapy, and the infiltration into the superior mesenteric plexus had also reduced. Therefore, the patient underwent subtotal stomach-preserving pancreatoduodenectomy and D2 lymph node dissection. The histopathological findings were invasive ductal carcinoma with R0 radical resection. The efficacy of preoperative adjuvant chemotherapy for BR pancreatic cancer has not been established yet, but improving the R0 resection rate with preoperative chemotherapy may contribute to an improvement in the outcome of pancreatic cancer.

[Significance of Transcatheter Arterial Chemoembolization for BCLC Stage B Hepatocellular Carcinoma with Mal-Nutrition].

Background and Aim: The recommendedind ication of transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC)is Barcelona Clinic Liver Cancer(BCLC)stage B HCC. But there are some cases in which we do not perform TACE because of liver damage with malnutrition in stage B. So we examined whether branched-chain amino acid (BCAA)improve nutritional status and perform TACE to contribute the prolongation of HCC survival. METHODS: This study included8 8 patients treatedfor liver cirrhosis with HCC. All patients initially receivedBCAA granules. In patients with unchangedor decreasedAlb levels, BCAA granules were discontinuedandBCAA enrichednutrient was started. TACE for HCC were performedin those with an improvedChild -Pugh score. RESULTS: TACE were performedfollowing the aggressive intervention with BCAA nutritional education in 66 of 88(75%)patients. Finally, overall survival time was significantly extended in TACE group(p<0.0001). CONCLUSION: Timely aggressive nutritional intervention in BCLC stage B HCC, early partial replacement with BCAA enrichednutrient before TACE may consequently contribute to improvement of the treatment outcome of HCC.

[Analysis of the Relationship between the Change of Drain Amylase Value and Postoperative Pancreatic Fistula after Pancreaticoduodenectomy].

To diagnose postoperative pancreatic fistula(POPF)after pancreaticoduodenectomy(PD)during early post operative days, we evaluatedwhether a change in drain amylase value(DAV), WBC value, or CRP value predicted clinically significant POPF. One hundred thirty patients underwent substomach preserving PD(SSPPD)from 2005 to 2016 in our institution andwe examinedDAV, WBC, andCRP values at POD 1, 3, and 5. Seventy-five patients(57.7%)were equivalent to ISGPF grade A at POD 3.We analyzedthese 75 cases by following 5 factors(DAV at POD 3>1,500 U/L, DAV at POD 5>1,000 U/L,WBC value at POD 5≤9,000/mL, DAV of POD 5 decreased to 1/3 from DAV of POD 3, CRP value not improved≥50%from POD 3 to 5) andwere concernedwith the crisis of the grade B/C POPF at final diagnosis after POD 5. In conclusion, DAV of POD 5 decreased to 1/3 from DAV of POD 3, andthe CRP value having not improved(≥50%from POD 3 to 5)were significant risk factors for POPF grade B andC by Cox proportional hazard models.

[Prediction of Treatment Effect of Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma Using Computed Tomography(CT)-Attenuation Value].

AIM: In general, transcatheter arterial chemoembolization(TACE)can obtain a high therapeutic effect on hypervascular tumors, but the definition of"hypervascular"is unclear. In this study, stainedtumor images on enhancedcomputedtomography( CT)were assessedaccord ing to CT-attenuation value. We investigatedwhether it is possible to estimate the treatment effect(TE)of TACE for hepatocellular carcinomas(HCCs). STUDY POPULATION AND METHODS: We studied 50 patients with unresectable HCCs who underwent TACE. A total of 141 tumors were diagnosed as HCC on enhanced CT. We measured andcalculatedthe ratios of CT-attenuation values of HCCs in the arterial phase to normal enhancedliver parenchyma in the portal phase(CT value ratio). We then evaluatedTE on each target nodule by enhancedCT, to examine the correlation between TE andthe CT value ratio. RESULTS: The CT-attenuation values were 119(range 61-180)hounsfieldunits(HU)for HCC and8 3(49-141)HU for liver parenchyma, andthe CT value ratio was 1.47(0.7-2.6). TE was positively correlatedwith the CT value ratio(p=0.0005). The cut-off value that suggestedfavorable results for TACE was 1.7 by receiver operating characteristic(ROC)analysis. CONCLUSION: The CT value ratio is useful for recognition of hypervascular tumors. We obtained favorable results in cases with a CT value ratio of 1.7 or more.

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.

Anesthesia-free In-office Hysteroscopic Morcellation for Endometrial Polyps: A Prospective Study.

Objectives: The objective of the study was to evaluate the feasibility and quality of anesthesia-free in-office hysteroscopic morcellation for the treatment of endometrial polyps. Materials and Methods: A prospective, single-center, open-label, single-arm clinical trial was conducted to evaluate the efficacy of hysteroscopic morcellation for endometrial polyps or retained products of conception. All surgical procedures were performed using the TruClear™ 5C system in the office setting without anesthesia. The primary endpoint was the success rate of surgery, defined as the completion of the operation. The secondary endpoints were operating time, fluid deficit, adverse events, pain evaluated by Visual Analog Scale (VAS) scores, and recurrence rate. Results: Ninety-five patients underwent hysteroscopic morcellation without anesthesia and received the treatment. The success rate of surgery was 100% (95/95), and the mean operating time was 7.3 min. Adverse events occurred in only 2.1% (2/95), with vasovagal reflex. The mean VAS scores during the procedure ranged from 2.4 to 3.1, and the recurrence rate after 6 months was 2.1% (1/47), with a pregnancy rate of 33% (11/33). When comparing nulliparous and parous patients, the success rate and the operating time were equivalent, and the mean VAS scores during the procedure were both within tolerable levels but significantly higher in nulliparous patients (3.3-4.5 vs. 1.6-1.9, P < 0.001). Conclusion: This study demonstrated that anesthesia-free in-office hysteroscopic morcellation for endometrial polyps can be safely performed with feasible quality and only tolerable pain. This less-invasive procedure is expected to become more widespread in future.

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.

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.

Fabrication and histological evaluation of a self-setting granular cement using calcium sulfate hemihydrate granules with different pore distribution.

Granular type of bone substitutes is currently used in the field of dentistry to restore alveolar bone defects. However, the migration of the granules from the implantation site is still an unresolved issue. In this study, the feasibility to fabricate self-setting calcium sulfate hemihydrate (CSH) granules using different ranges of loading pressure: CSH(0), CSH(50), CSH(100), and CSH(150) was investigated with the hypothesis that CSH granules with reduced microporosity can inhibit the rapid dissolution rate of the calcium sulfate dihydrate (CSD) set blocks and induce bone regeneration. After 4 weeks of implantation, the granules were mostly replaced with new bone although no significant differences were observed. Nevertheless, the granules demonstrated the ability to set within the bone defect. It is therefore concluded that the setting ability of calcium sulfate can contribute to address the issue of migration of the granules and provide a useful guide for designing setting bone substitutes.

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.

Silver phosphate-modified carbonate apatite honeycomb scaffolds for anti-infective and pigmentation-free bone tissue engineering.

Bone regeneration using synthetic materials has a high rate of surgical site infection, resulting in severe pain for patients and often requiring revision surgery. We propose Ag3PO4-based surface modification and structural control of scaffolds for preventing infections in bone regeneration. We demonstrated the differences in toxicity and antibacterial activity between in vitro and in vivo studies and determined the optimal silver content in terms of overall anti-infection effects, bone regeneration, toxicity, and pigmentation. A honeycomb structure comprising osteoconductive and resorbable carbonate apatite (CAp) was used as the base scaffold. CAp in the scaffold surface was partially replaced with different concentrations of Ag3PO4 via controlled dissolution-precipitation reactions in an AgNO3 solution. Both bone regeneration and infection prevention were achieved at 860-2300 ppm of silver. Despite the absence of Ag3PO4, honeycomb scaffolds were less susceptible to infection, even under conditions where infection occurs in clinically used three-dimensional porous scaffolds. Regardless of in vitro cytotoxicity at >5200 ppm of silver, increasing the silver content to 21,000 ppm did not adversely affect in vivo bone formation and scaffold resorption or cause acute systemic toxicity. Rather, bone formation was enhanced with 5200 ppm of silver. However, pigmentation was observed at that concentration. Hence, we concluded that the optimal silver concentration range is 860-2300 ppm for anti-infective and pigmentation-free bone regeneration. Bone regeneration was achieved via surface modification, resulting in the rapid release of silver ions immediately after implantation, followed by gradual release over several months. The scaffold structure may also aid in preventing bacterial growth within the scaffolds.