Association of high kinesiophobia and pain catastrophizing with quality of life in severe hip osteoarthritis: a cross-sectional study.

BACKGROUND: While fear of movement is an important predictor of pain and disability in osteoarthritis (OA), its impact on patients with hip OA remains uncertain. This study aimed to determine whether fear of movement, evaluated by the Tampa Scale for Kinesiophobia (TSK)-11, and pain catastrophizing, evaluated by the Pain Catastrophizing Scale (PCS), were associated with quality of life (QOL) in patients with hip OA. METHODS: This cross-sectional study was conducted between November 2017 and December 2018. Ninety-one consecutively enrolled patients with severe hip OA were scheduled for primary unilateral total hip arthroplasty. The EuroQOL-5 Dimensions questionnaire was used to measure general QOL. The Japanese Orthopedic Association Hip Disease Evaluation Questionnaire was used to assess disease-specific QOL. The covariates included age, sex, body mass index (BMI), pain intensity, high pain catastrophizing (PCS ≥ 30), and high kinesiophobia (TSK-11 ≥ 25). Variables were subjected to multivariate analysis using each QOL scale. RESULTS: In multiple regression analysis, pain intensity, high pain catastrophizing, and BMI were independently correlated with the disease-specific QOL scale. High pain catastrophizing, pain intensity, and high kinesiophobia were independently correlated with the general QOL scale. CONCLUSIONS: High pain catastrophizing (PCS ≥ 30) was independently associated with disease and general QOL scales. High kinesiophobia (TSK-11 ≥ 25) was independently associated with the general QOL scale in preoperative patients with severe hip OA.

A dynamic pedicle screw system using polyethylene insert for the lumbar spine.

Rigid spinal fusion with instrumentation has been widely applied in treating degenerative spinal disorders and has shown excellent and stable surgical results. However, adjacent segment pathology or implants' loosening could be problematic due to the spine's segmental fusion. Therefore, this study verified a novel concept for posterior stabilization with polyethylene inserts inside a pedicle screw assembly using bone models. We observed that although the gripping capacity of the dynamic pedicle screw system using a tensile and compression tester was less than half that of the rigid pedicle screw system, the flexion-extension moment of the dynamic pedicle screws was significantly lower than that of the rigid pedicle screws. Furthermore, while the bending force of the rigid pedicle screw assembly increased linearly with an increase in the bending angle throughout the test, that of the dynamic pedicle screw assembly also increased linearly until a bending angle of 2.5° was reached. However, this angle decreased at a bending angle of more than 2.5°. Additionally, the fatigue test of 1.0 × 106 cycles showed that the pull-out force of the dynamic pedicle screws from two different polyurethane foam blocks was significantly higher than that of the rigid pedicle screws. Therefore, based on our results, we propose that the device can be applied in clinical cases to reduce screw loosening and adjacent segment pathology.

Regulation of osteoarthritis development by ADAM17/Tace in articular cartilage.

INTRODUCTION: A disintegrin and metalloproteinase 17 (Adam17), also known as TNFα-converting enzyme (Tace), is a membrane-anchored protein involved in shedding of TNF, IL-6 receptor, ligands of epidermal growth factor receptor (EGFR), and Notch receptor. This study aimed to examine the role of Adam17 in adult articular cartilage and osteoarthritis (OA) pathophysiology. MATERIALS AND METHODS: Adam17 expression was examined in mouse knee joints during OA development. We analyzed OA development in tamoxifen-inducible chondrocyte-specific Adam17 knockout mice of a resection of the medial meniscus and medial collateral ligament (medial) model, destabilization of the medial meniscus (DMM) model, and aging model. We analyzed downstream pathways by in vitro experiments, and further performed intra-articular administration of an Adam17 inhibitor TAPI-0 for surgically induced mouse OA. RESULTS: Adam17 expression in mouse articular cartilage was increased by OA progression. In all models, Adam17 knockout mice showed ameliorated progression of articular cartilage degradation. Adam17 knockout decreased matrix metallopeptidase 13 (Mmp13) expression in both in vivo and in vitro experiments, whereas Adam17 activation by phorbol-12-myristate-13-acetate (PMA) increased Mmp13 and decreased aggrecan in mouse primary chondrocytes. Adam17 activation enhanced release of soluble TNF and transforming growth factor alpha, a representative EGF ligand, from mouse primary chondrocytes, while it did not change release of soluble IL-6 receptor or nuclear translocation of Notch1 intercellular domain. Intra-articular administration of the Adam17 inhibitor ameliorated OA progression. CONCLUSIONS: This study demonstrates regulation of OA development by Adam17, involvement of EGFR and TNF pathways, and the possibility of Adam17 as a therapeutic target for OA.

Efficacy of hydrated phospholipid polymer interfaces between all-polymer bearings for total hip arthroplasty.

Measurements of wear resistance and metal ion release are important for designing bearing couples or interfaces in total hip arthroplasty (THA). In this study, we investigated wear resistance and metal ion release of surface-modified metal-free all-polymer hip bearings, such as poly(ether-ether-ketone), (PEEK) on cross-linked polyethylene (PEEK-on-CLPE), with a hydrated gel-like surface layer, to propose an improved alternative to the conventional materials used to design THA bearings. The PEEK surface resulted in less metal ion release than the cobalt-chromium-molybdenum (Co-Cr-Mo) alloy surface owing to the lack of metal. The PEEK-on-CLPE bearing (6.33 mg/106 cycles) had lower wear (rate) than the bearing with Co-Cr-Mo alloy-on-CLPE (10.47 mg/106 cycles) under controlled laboratory conditions; the wear performance of the all-polymer hip bearings was further improved with hemi- or both-surface modified with a hydrated poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) layer (3.74 and 3.06 mg/106 cycles, respectively). The PMPC-grafted interface of PEEK-on-CLPE will be especially suitable for THA candidates. This study is of key importance for the design of lifelong THA and a better understanding of the limitations resulting from using PEEK. Further studies are necessary to evaluate the possibility of using this material in artificial hips.

Comparison between cup implantations during total hip arthroplasty with or without a history of rotational acetabular osteotomy.

INTRODUCTION: Total hip arthroplasty (THA) after rotational acetabular osteotomy (RAO) is technically demanding because of the characteristic acetabular morphology after RAO. The present study aimed to investigate the differences in the three-dimensional cup position between THA after RAO and primary THA. MATERIALS AND METHODS: We analysed the pre-operative and post-operative computed tomography (CT) data of 120 patients (20 patients after RAO and 100 patients without a history of RAO) who underwent THA between January 2017 and June 2018. We evaluated radiographic parameters, including acetabular anteversion, antero-posterior distance at the level of the femoral head centre, the presence of anterior acetabular osteophyte and/or rotated fragment during RAO from the CT data. Additionally, operative data and clinical scores were also evaluated. RESULTS: Although we found no significant differences in any clinical parameters, there were significant differences in radiographic parameters and operative data. The morphology of the acetabulum was significantly retroverted, and the antero-posterior distance was longer in patients after RAO, compared to the implanted cup. Additionally, longer operative time was necessary for such patients. These results reflect the atypical acetabular morphology after RAO, and emphasize that care should be taken to avoid anterior bony impingement and post-operative dislocation. CONCLUSION: For cup implantation during THA after RAO, surgeons should acknowledge the atypical morphology of the acetabulum and not be misled by its visual shape.

Characteristics of three-dimensional acetabular morphology of patients with excellent outcome after rotational acetabular osteotomy over 20 years.

BACKGROUND: Rotational acetabular osteotomy (RAO) is a type of pelvic osteotomy performed to improve the acetabular bony coverage against the femoral head for patients with acetabular dysplasia. The acetabular bony coverage is ideally evaluated three-dimensionally; however, there is a paucity of published data regarding three-dimensional morphology in patients with long-term excellent outcome after RAO. The present study investigated the characteristics of three-dimensional acetabular morphology with long-term excellent outcome after RAO in comparison to patients with normal hip joints and those converted to total hip arthroplasty (THA) after RAO because of osteoarthritis (OA) progression. METHODS: Anteroposterior plain radiograph and computed tomography data of 57 hip joints (17 joints with excellent outcome 20 years or more after RAO, 16 normal joints, and 20 joints converted to THA after RAO) were analyzed. The two-dimensional lateral center-edge (CE) angle from plain radiographs and acetabular anteversion, anterior acetabular sector angle, and posterior sector angle from computed tomography (CT) images were calculated. RESULTS: Compared with patients converted to THA, all parameters in patients with long-term excellent outcome after RAO were similar to those in patients with normal hip joints, particularly in the three-dimensional analyses. The anterior bony coverage was excessive, whereas the posterior bony coverage was deficient in patients converted to THA after RAO. Anterior bony impingement and posterior instability may be the cause of OA progression after RAO. CONCLUSION: Caution must be taken to avoid rotating the separated fragment excessively to the anterior direction during RAO to prevent OA progression and achieve long-term excellent outcome.

2-Methacryloyloxyethyl Phosphorylcholine Polymer Coating Inhibits Bacterial Adhesion and Biofilm Formation on a Suture: An In Vitro and In Vivo Study.

Initial bacterial adhesion to medical devices and subsequent biofilm formation are known as the leading causes of surgical site infection (SSI). Therefore, inhibition of bacterial adhesion and biofilm formation on the surface of medical devices can reduce the risk of SSIs. In this study, a highly hydrophilic, antibiofouling surface was prepared by coating the bioabsorbable suture surface with poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate) (PMB). The PMB-coated and noncoated sutures exhibited similar mechanical strength and surface morphology. The effectiveness of the PMB coating on the suture to suppress adhesion and biofilm formation of methicillin-resistant Staphylococcus aureus and methicillin-susceptible Staphylococcus aureus was investigated both in vitro and in vivo. The bacterial adhesion test revealed that PMB coating significantly reduced the number of adherent bacteria, with no difference in the number of planktonic bacteria. Moreover, fluorescence microscopy and scanning electron microscopy observations of adherent bacteria on the suture surface after contact with bacterial suspension confirmed PMB coating-mediated inhibition of biofilm formation. Additionally, we found that the PMB-coated sutures exhibited significant antibiofouling effects in vivo. In conclusion, PMB-coated sutures demonstrated bacteriostatic effects associated with a highly hydrophilic, antibiofouling surface and inhibited bacterial adhesion and biofilm formation. Therefore, PMB-coated sutures could be a new alternative to reduce the risk of SSIs.

Midterm results of revision total hip arthroplasty for migrated bipolar hemiarthroplasty in patients with hip osteoarthritis using cementless cup with the rim-fit technique.

PURPOSE: The results of reamed bipolar hemiarthroplasty (BHA) in patients with hip osteoarthritis (OA) are reported to be unfavorable. Acetabular reaming for sufficient bony coverage caused bipolar head migration into the superomedial direction, and most patients required revision surgeries. Several methods are applicable to treat decreased bone stock. This study aimed to investigate the midterm results of revision surgeries using the cementless cup with the rim-fit technique. METHODS: Between 1996 and 2014, acetabular revision surgeries using the cementless cup with the rim-fit technique were performed in 86 hips (74 patients). We evaluated radiographic outcomes, including positional change of the rotation center of the artificial femoral head, presence of implant loosening, and filling of the initial gap. We also evaluated clinical outcomes, including the Harris hip score (HHS), and postoperative complications. RESULTS: The average positional changes from BHA to prerevision surgeries were 8.0 mm superiorly and 4.1 mm medially. The average changes from prerevision to postrevision surgeries were 3.7 mm inferiorly and 2.4 mm laterally. No implant loosening was found in all cases; the initial gap between the acetabular host bone and the acetabular cup was filled in 53 (93%) among 57 hips. The average HHS improved from 65.9 before revision surgeries to 83.8 in the latest follow-up. Dislocation and postoperative periprosthetic fracture occurred in two and five hips, respectively; no cases required rerevision surgeries. CONCLUSION: There were favorable midterm results of the revision total hip arthroplasty for migrated BHA in patients with hip OA using cementless cup with the rim-fit technique.

Hydrated Phospholipid Polymer Gel-Like Layer for Increased Durability of Orthopedic Bearing Surfaces.

Recently, traditional strategies for manipulating orthopedic bearing substrates have attempted to improve their wear resistance by adjusting polyethylene substrate through cross-linking and antioxidant blending. However, further research is required on the substrate, as well as the surface focused on the structure and role of articular cartilage. We therefore develop an orthopedic bearing surface comprising a nanometer-scale hydrated gel-like layer by grafting highly hydrophilic poly(2-methacryloyloxyethyl phosphorylcholine), with the aim of mimicking the lubrication mechanism of articular cartilage, and investigate its surface characteristics, bulk characteristics, and behavior under load bearing conditions upon accelerated aging. Neither the hydrophilicity nor lubricity of the gel-like surface was influenced by accelerated aging; instead, high stability was revealed, even under strong oxidation conditions. The characteristics of the hydrated gel-like surface potentiated the wear resistance of the cross-linked polyethylene liner, irrespective of accelerated aging. These results suggest that the hydrated gel-like surface enhances the longevity of cross-linked polyethylene bearings even under load-bearing conditions. Furthermore, the inflection point on the time series of wear can be a suitable indicator of the durability of the life-long protectant. In conclusion, the hydrated gel-like surface can positively increase orthopedic implant durability.

Effects of a roughened femoral head and the locus of grafting on the wear resistance of the phospholipid polymer-grafted acetabular liner.

Although laboratory tests and mid-term clinical outcomes show the clinical safety and remarkable wear resistance of the highly cross-linked polyethylene (HXLPE) acetabular liner with a nanometer-scaled graft layer of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), the wear resistance of the layer under severe abrasive conditions is concerning. We evaluated the effects of a roughened femoral head and the grafting locus on the wear resistance of the PMPC-grafted HXLPE liner and the effect of PMPC grafting on wear resistance of the HXLPE substrate by removing the PMPC-grafted layer using a severely roughened femoral head. Against a moderately roughened femoral head, the PMPC-grafted HXLPE liner showed negative wear, although an untreated HXLPE liner increased the wear by 154.1% compared with wear against a polished femoral head, confirming that PMPC grafts were unaffected. Against a severely roughened femoral head, the PMPC-grafted layer of the head contact area might be removed under severe conditions. However, the wear rate was reduced by 52.5% compared to that of untreated HXLPE liners. Moreover, the head non-contact area-modified PMPC-grafted HXLPE liner against a polished femoral head reduced the wear by 76.8% compared with untreated HXLPE liner; thus, this area may be also important in the development of fluid-film lubrication. STATEMENT OF SIGNIFICANCE: Here we describe effects of a roughened femoral head and the locus of grafting on the wear-resistance of the phospholipid polymer grafted highly cross-linked polyethylene (PMPC-HXLPE) liner. Against a moderately roughened femoral head, the PMPC-HXLPE liner showed negative wear, confirming that PMPC grafts were unaffected. After removing the PMPC layer of the head contact area using a severely roughened femoral head, the wear rate not only exceeded that of untreated HXLPE liners, but was reduced by 52.5%, confirming that PMPC grafting does not affect the wear-resistance of the HXLPE substrate. In addition, the head non-contact area-modified PMPC-HXLPE liner reduced the wear by 76.8%. Thus, this area may also may be important in the development of fluid-film lubrication.

Multi-layered PLLA-nanosheets loaded with FGF-2 induce robust bone regeneration with controlled release in critical-sized mouse femoral defects.

To overcome clinical issues caused by large bone defects and subsequent nonunion, various approaches to bone regeneration have been researched, including tissue engineering, biomaterials, stem cells and drug screening. Previously, we developed a free-standing biodegradable polymer nanosheet composed of poly(L-lactic acid) (PLLA) using a simple fabrication process consisting of spin-coating and peeling techniques. We reported that sandwich-type PLLA nanosheets loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) displayed long-lasting, sustained release of rhBMP-2, and markedly enhanced bone regeneration in mouse calvarial bone defects. Here, we fabricated multi-layered nanosheets loaded with fibroblast growth factor-2 (FGF-2), and investigated their application for long bone regeneration. Subcutaneously implanted tri-layered PLLA nanosheets displayed sustained release of loaded rhFGF-2 for about 2 weeks. Next, we prepared critical-sized mouse femoral defects and implanted mono- or tri-layered nanosheets, or a gelatin hydrogel with rhFGF-2. Amongst these conditions, the tri-layered nanosheet most efficiently induced bone regeneration. Indeed, bone regeneration was enhanced even after 4 weeks in the tri-layered nanosheet group, and was accompanied by FGFR1 activation and subsequent osteoblast differentiation. Multi-layered PLLA nanosheets loaded with rhFGF-2 may be useful for bone regenerative medicine. Furthermore, the multi-layered PLLA nanosheet structure may potentially be applied as a potent sustained-release carrier. STATEMENTS OF SIGNIFICANCE: Here, we describe multi-layered poly(L-lactic acid) (PLLA) nanosheets loaded with recombinant human fibroblast growth factor-2 (rhFGF-2) as a modified sustained-release carrier for bone regeneration. In vivo imaging system analysis revealed that subcutaneously implanted tri-layered PLLA nanosheets displayed sustained release of loaded rhFGF-2 for 2 weeks. In critical-sized mouse femoral defects, tri-layered nanosheets loaded with rhFGF-2 most efficiently induced bone regeneration. Notably, bone regeneration was enhanced even after 4 weeks in the tri-layered nanosheet group, and was accompanied by FGFR1 activation and subsequent osteoblast differentiation. Multi-layered PLLA nanosheets loaded with rhFGF-2 may be useful for bone regenerative medicine. Furthermore, the multi-layered PLLA nanosheet structure may potentially be applied as a potent sustained-release carrier.

Evaluation of the three-dimensional bony coverage before and after rotational acetabular osteotomy.

PURPOSE: Rotational acetabular osteotomy is a type of pelvic osteotomy that involves rotation of the acetabular bone to improve the bony coverage of the femoral head for patients with acetabular dysplasia. Favourable post-operative long-term outcomes have been reported in previous studies. However, there is a paucity of published data regarding three-dimensional bony coverage. The present study investigated the three-dimensional bony coverage of the acetabulum covering the femoral head in hips before and after rotational acetabular osteotomy and in normal hips. METHODS: The computed tomography data of 40 hip joints (12 joints before and after rotational acetabular osteotomy; 16 normal joints) were analyzed. The three-dimensional bony coverage of each joint was evaluated using original software. RESULTS: The post-operative bony coverage improved significantly compared with pre-operative values. In particular, the anterolateral aspect of the acetabulum tended to be dysplastic in patients with acetabular dysplasia compared to those with normal hip joints. However, greater bony coverage at the anterolateral aspect was obtained after rotational acetabular osteotomy. Meanwhile, the results of the present study may indicate that the bony coverage in the anterior aspect may be excessive. CONCLUSION: Three-dimensional analysis indicated that rotational acetabular osteotomy achieved favorable bony coverage. Further investigations are necessary to determine the ideal bony coverage after rotational acetabular osteotomy.

A phospholipid polymer graft layer affords high resistance for wear and oxidation under load bearing conditions.

Manipulating the surface and substrate of cross-linked polyethylene (CLPE) is an essential approach for obtaining life-long orthopedic bearings. We therefore proposed a bearing material comprised of an antioxidative substrate generated by vitamin E blending (HD-CLPE[VE]) with a poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-grafted surface, and investigated its wear resistance and oxidative stability under accelerated aging and load bearing conditions. Neither the hydration nor friction kinetics of the molecular network structure of the PMPC-grafted surface or the HD-CLPE(VE) substrate were influenced by accelerated aging but rather exhibited high stability even under high oxidation conditions. The characteristics of the PMPC-grafted surface improved the wear and impact fatigue resistance of the HD-CLPE(VE) liner regardless of accelerated aging. Notably, the PMPC-grafted surface was found to affect the potential oxidative stability at the rim part of the acetabular liner. PMPC chains serve several important functions on the surface regardless of load bearing, such as high lubricity or low lipophilicity attributed to phosphorylcholine groups and/or surrounding water-fluid film, and suppression of lipid diffusion attributed to methacrylate main chains on the surface. Together, these results provide preliminary evidence that the PMPC graft layer and vitamin E-blended substrate might positively affect the extent of orthopedic implant durability.

Wear resistance of poly(2-methacryloyloxyethyl phosphorylcholine)-grafted carbon fiber reinforced poly(ether ether ketone) liners against metal and ceramic femoral heads.

Younger, active patients who undergo total hip arthroplasty (THA) have increasing needs for wider range of motion and improved stability of the joint. Therefore, bearing materials having not only higher wear resistance but also mechanical strength are required. Carbon fiber-reinforced poly(ether ether ketone) (CFR-PEEK) is known as a super engineering plastic that has great mechanical strength. In this study, we focused on poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-grafted CFR-PEEK and investigated the effects of PMPC grafting and the femoral heads materials on the wear properties of CFR-PEEK liners. Compared with untreated CFR-PEEK, the PMPC-grafted CFR-PEEK surface revealed higher wettability and lower friction properties under aqueous circumstances. In the hip simulator wear test, wear particles generated from the PMPC-grafted CFR-PEEK liners were fewer than those of the untreated CFR-PEEK liners. There were no significant differences in the size and the morphology of the wear particles between the differences of PMPC-grafting and the counter femoral heads. Zirconia-toughened alumina (ZTA) femoral heads had significantly smoother surfaces compared to cobalt-chromium-molybdenum alloy femoral heads after the hip simulator test. Thus, we conclude that the bearing combination of the PMPC-grafted CFR-PEEK liner and ZTA head is expected to be a lifelong bearing interface in THA. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1028-1037, 2018.

Reducing fretting-initiated crevice corrosion in hip simulator tests using a zirconia-toughened alumina femoral head.

Taper fretting corrosion is considered a potentially limiting factor for total hip arthroplasty longevity. Recently, attention has been focused on new materials for ceramic femoral heads, for example, zirconia-toughened alumina (ZTA), since they have an alternative bearing surface that can improve the wear resistance. Moreover, ceramics have high chemical stability and corrosion resistance. In this study, we evaluated the effects of ZTA and Co-Cr-Mo alloy femoral heads on their taper fretting and/or corrosion characteristics under a controlled hip simulator test. After the test, less fretting and corrosion were observed in the taper surface of the trunnion against the ZTA femoral head than for that against the Co-Cr-Mo alloy femoral head. In addition, corrosion damages were only observed in the lateral-distal taper surface (noncontact area) of the trunnion in the Co-Cr-Mo alloy femoral head group. The ZTA femoral head group also eliminated the potential for Co ion release into the lubricants from taper corrosion, reducing the possibility of adverse local tissue inflammatory responses. In conclusion, ZTA femoral heads showed markedly less fretting corrosion compared to Co-Cr-Mo alloy femoral heads and have a lower potential for metal ion release. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2815-2826, 2018.

The effects of presence of a backside screw hole on biotribological behavior of phospholipid polymer-grafted crosslinked polyethylene.

One of the important factors in determining the success of joint replacement is the wear performance of polyethylene. Although highly crosslinked polyethylene (CLPE) is presently used, it is still not adequate. We have developed a surface modification technology using poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) in an attempt to improve wear performance. In this study, we evaluated the wear and creep deformation resistances of 3-mm and 6-mm thick PMPC-grafted CLPE disks, set on a metal back-plate, with and without a sham screw hole. The gravimetric wear and volumetric change of the disks were examined using a multidirectional pin-on-disk tester. PMPC grafting decreased the gravimetric wear of CLPE regardless of the presence of a screw hole, and did not affect the volumetric change. The volumetric change in the bearing and backside surfaces of the 3-mm thick disk with a screw hole was much larger than that of those without a screw hole or those of the 6-mm thick disk, which was caused by creep deformation. PMPC grafting on the bearing surface can be a material engineering approach to reduce the wear without changing the creep deformation resistance, and is a promising surface modification technology that can be used to increase the longevity of various artificial joints. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 610-618, 2018.

Sandwich-type PLLA-nanosheets loaded with BMP-2 induce bone regeneration in critical-sized mouse calvarial defects.

To overcome serious clinical problems caused by large bone defects, various approaches to bone regeneration have been researched, including tissue engineering, biomaterials, stem cells and drug screening. Previously, we developed a free-standing biodegradable polymer nanosheet composed of poly(L-lactic acid) (PLLA) using a simple fabrication process consisting of spin-coating and peeling techniques. Here, we loaded recombinant human bone morphogenetic protein-2 (rhBMP-2) between two 60-nm-thick PLLA nanosheets, and investigated these sandwich-type nanosheets in bone regeneration applications. The PLLA nanosheets displayed constant and sustained release of the loaded rhBMP-2 for over 2months in vitro. Moreover, we implanted the sandwich-type nanosheets with or without rhBMP-2 into critical-sized defects in mouse calvariae. Bone regeneration was evident 4weeks after implantation, and the size and robustness of the regenerated bone had increased by 8weeks after implantation in mice implanted with the rhBMP-2-loaded nanosheets, whereas no significant bone formation occurred over a period of 20weeks in mice implanted with blank nanosheets. The PLLA nanosheets loaded with rhBMP-2 may be useful in bone regenerative medicine; furthermore, the sandwich-type PLLA nanosheet structure may potentially be applied as a potent prolonged sustained-release carrier of other molecules or drugs. STATEMENTS OF SIGNIFICANCE: Here we describe sandwich-type poly(L-lactic acid) (PLLA) nanosheets loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a novel method for bone regeneration. Biodegradable 60-nm-thick PLLA nanosheets display strong adhesion without any adhesive agent. The sandwich-type PLLA nanosheets displayed constant and sustained release of the loaded rhBMP-2 for over 2months in vitro. The nanosheets with rhBMP-2 markedly enhanced bone regeneration when they were implanted into critical-sized defects in mouse calvariae. In addition to their application for bone regeneration, PLLA nanosheets may be useful for various purposes in combination with various drugs or molecules, because they displays excellent capacity as a sustained-release carrier.

Clinical and Radiographic Outcomes of Total Hip Arthroplasty With a Specific Liner in Small Asian Patients: Influence of Patient-Related, Implant-Related, and Surgical Factors on Femoral Head Penetration.

BACKGROUND: We evaluated the clinical and radiographic outcomes, including femoral head penetration, of total hip arthroplasty performed using a specific polyethylene (PE) liner in small Asian patients at 10 years after the index surgery. In addition, we investigated whether femoral head penetration was affected by patient-related, implant-related, and surgical factors. METHODS: Between August 2002 and June 2005, for cementless primary total hip arthroplasty, we used acetabular PE liners that were manufactured from GUR 1050 resin, machined from isostatic compression-molded bar stock, and sterilized with a gamma ray irradiation in argon gas. We assessed 82 hips in 78 patients who received these liners. RESULTS: The mean Harris hip score improved from 41.0 preoperatively to 84.5 at 10 years postoperatively. Periprosthetic osteolysis was observed in 7 hips (9.8%). No acetabular component migration was detected, and no revision surgery was performed 10 years postoperatively. The mean steady-state wear rate was 0.031 mm/y, which was lower than the wear rate for other conventional PE liners of the previous studies. Among the patient-related, implant-related, and surgical factors, sex was significantly associated with the mean steady-state wear rate, with a higher rate in male patients than in female patients. CONCLUSION: PE acetabular liners used in small Asian patients show similar clinical outcomes and reduced wear compared with those of other liners. In addition, sex is significantly associated with the mean steady-state wear rate, and the steady-state wear rate is higher in male patients than in female patients.

A hydrated phospholipid polymer-grafted layer prevents lipid-related oxidative degradation of cross-linked polyethylene.

The surface and substrate of a cross-linked polyethylene (CLPE) liner are designed to achieve resistance against oxidative degradation in the construction of hip joint replacements. In this study, we aimed to evaluate the oxidative degradation caused by lipid absorption of a highly hydrophilic nanometer-scaled thickness layer prepared by grafting a poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) layer and a high-dose gamma-ray irradiated CLPE with vitamin E blending (HD-CLPE[VE]). The HD-CLPE(VE) and PMPC-grafted HD-CLPE(VE) exhibited extremely high oxidation resistance regardless of lipid absorption, even though residual-free radical levels were detectable. The water wettability of the PMPC-grafted CLPE and PMPC-grafted HD-CLPE(VE) surfaces was considerably greater than that of untreated surfaces. The hydrated PMPC-grafted layer also exhibited extremely low solubility for squalene. Lipids such as squalene and cholesterol esters diminished the oxidation resistance of CLPE despite the vitamin E improvement. Notably, the PMPC-grafted surface was resistant to lipid absorption and diffusion as well as subsequent lipid-related oxidative degradation, likely because of the presence of the hydrated PMPC-grafted layer. Together, these results provide preliminary evidence that the resistance against lipid absorption and diffusion of a hydrated PMPC-grafted layer might positively affect the extent of resistance to the in vivo oxidation of orthopedic implants.

Clinical safety and wear resistance of the phospholipid polymer-grafted highly cross-linked polyethylene liner.

To reduce the production of wear particles and subsequent aseptic loosening, we created a human articular cartilage-mimicked surface for a highly cross-linked polyethylene liner, whose surface grafted layer consisted of a biocompatible phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine). Although our previous in vitro findings showed that poly(2-methacryloyloxyethyl phosphorylcholine)-grafted particles were biologically inert and caused no subsequent bone resorptive responses, and poly(2-methacryloyloxyethyl phosphorylcholine) grafting markedly decreased wear in hip joint simulator tests, the clinical safety, and in vivo wear resistance of poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners remained open to question. Therefore, in the present study, we evaluated clinical and radiographic outcomes of poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners 5 years subsequent to total hip replacement in 68 consecutive patients. No reoperation was required for any reason, and no adverse events were associated with the implanted liners. The average Harris Hip Score increased from 38.6 preoperatively to 96.5 5 years postoperatively, and health-related quality of life, as indicated by the Short Form 36 Health Survey, improved. Radiographic analyses showed no periprosthetic osteolysis or implant migration. Between 1 and 5 years postoperatively, the mean steady-state wear rate was 0.002 mm/year, which represented a marked reduction relative to other highly cross-linked polyethylene liners, and appeared to be unaffected by patient-related or surgical factors. Although longer follow up is required, poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners improved mid-term clinical outcomes. The clinical safety and wear-resistance results are encouraging with respect to the improvement of long-term clinical outcomes with poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2007-2016, 2017.