In vivo implant fixation of carbon fiber‐reinforced PEEK hip prostheses in an ovine model

Carbon fiber‐reinforced polyetheretherketone (CFR/PEEK) is theoretically suitable as a material for use in hip prostheses, offering excellent biocompatibility, mechanical properties, and the absence of metal ions. To evaluate in vivo fixation methods of CFR/PEEK hip prostheses in bone, we examined radiographic and histological results for cementless or cemented CFR/PEEK hip prostheses in an ovine model with implantation up to 52 weeks. CFR/PEEK cups and stems with rough‐textured surfaces plus hydroxyapatite (HA) coatings for cementless fixation and CFR/PEEK cups and stems without HA coating for cement fixation were manufactured based on ovine computed tomography (CT) data. Unilateral total hip arthroplasty was performed using cementless or cemented CFR/PEEK hip prostheses. Five cementless cups and stems and six cemented cups and stems were evaluated. On the femoral side, all cementless stems demonstrated bony ongrowth fixation and all cemented stems demonstrated stable fixation without any gaps at both the bone‐cement and cement‐stem interfaces. All cementless cases and four of the six cemented cases showed minimal stress shielding. On the acetabular side, two of the five cementless cups demonstrated bony ongrowth fixation. Our results suggest that both cementless and cemented CFR/PEEK stems work well for fixation. Cup fixation may be difficult for both cementless and cemented types in this ovine model, but bone ongrowth fixation on the cup was first seen in two cementless cases. Cementless fixation can be achieved using HA‐coated CFR/PEEK implants, even under load‐bearing conditions. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 485–492, 2013     

大段仿生活性人工骨修复犬长骨缺损的实验研究

[目的]观察大段活性人工骨对大动物骨缺损的修复效果,了解材料的降解性。[方法]以快速成形技术制备犬用PLLA.cTCP大段人工骨载体材料,按3 mg/块材料的标准复合rhBMP-2制备犬用大段活性人工骨。以犬桡骨2.0 cm骨缺损为实验模型,将大段活性人工骨(实验组)和单纯载体材料(对照组)植入骨缺损,通过影像学、组织学、生物力学检查评价骨缺损的修复效果,通过图像分析仪分析材料的降解情况。[结果]影像学检查表明,实验组术后12周骨痂与断端完全连接,术后24周骨痂塑形良好。对照组术后24周无骨痂生长,缺损未修复。组织学检查证明,实验组术后12周骨痂外层形成板层骨,中央形成小梁骨及骨髓组织,材料部分吸收;术后24周,骨痂板层骨致密,小梁骨减少,骨髓组织增多,材料进一步降解。对照组术后12周纤维组织将材料包裹并长入其中,材料部分降解;术后24周材料被纤维组织分割包裹,材料进一步降解。术后12周实验组和对照组的降解率分别为43.2%和35.7%,术后24周58.4%和45.4%。生物力学检测证明,术后24周实验组桡骨的抗弯强度超过正常骨的强度。[结论]PLLA.cTCP大段活性人工骨对大动物骨缺损有良好的修复效果,材料的降解性还需要改善。     

Augmentation of peri‐implant bone improves implant stability: Quantification using simulated bone loss

Low bone quality, such as induced by osteoporosis, is considered a main factor leading to failure of fracture fixations. Peri‐implant bone augmentation has been proposed as a means of reducing failure rates in osteoporotic bone by improving implant stability. The beneficial effects of pharmacological augmentation of bone in the immediate vicinity of the implant have been demonstrated. Yet, a quantitative understanding of the role of peri‐implant bone in implant stability is lacking. Therefore, the aim of our study was to quantify the effects of bone loss and peri‐implant bone augmentation on implant stability using image‐based finite element analyses. Using a validated model, we simulated how osteoporotic bone loss would affect implant stability in human humeral heads. We also quantified how augmentation of peri‐implant bone can enhance implant stability. Our simulations revealed that a 30% reduction in bone mass led to a 50% decrease in implant stability. We also found that peri‐implant bone augmentation increased implant stability and that the efficiency of bone augmentation decreased with increasing peri‐implant distance. These findings highlight the strong effect that bone loss has on implant fixation and the potential of peri‐implant bone augmentation for improving implant anchorage in low quality bone. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:178–184, 2012     

Massive bone reconstruction with heat‐treated bone graft loaded autologous bone marrow‐derived stromal cells and β‐tricalcium phosphate composites in canine models

Bone marrow‐derived stromal cells (BMSCs) contain mesenchymal stem cells that are capable of forming various mesenchymal tissues. We hypothesized that BMSCs and β‐tricalcium phosphate (β‐TCP) composites would promote the remodeling of large‐sized autologous devitalized bone grafts; therefore, the aim of this study was to evaluate the effects of the composites on the remodeling of autologous devitalized bone grafts. Autologous BMSCs cultured in culture medium containing dexamethasone (10^?7 M) were loaded into porous β‐TCP granules under low‐pressure. Theses BMSC/TCP composites were put into the bone marrow cavity of autologous heat‐treated bone (femoral diaphysis, 65‐mm long, 100°C, 30 min) and put back to the harvest site. In the contralateral side, β‐TCP without BMSC were used in the same manner as the opposite side as the control. Treatment with the BMSC/TCP composites resulted in a significant increase in thickness, bone mineral density, and matured bone volume of the cortical bone at the center of the graft compared to the control. Histological analysis showed matured regenerated bone in the BMSC loaded group. These results indicate that BMSC/TCP composites facilitated bone regeneration and maturation at the graft site of large‐sized devitalized bone. This method could potentially be applied for clinical use in the reconstruction of large bone defects such as those associated with bone tumors. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1308–1316, 2013

     

带蒂耳廓复合组织瓣Ⅰ期修复较大面积鼻翼缺损15例

目的介绍带蒂耳廓复合组织瓣Ⅰ期修复较大面积鼻翼缺损的新方法。方法利用眶上动脉和颞浅动脉吻合支的反流血运,形成带蒂的耳廓复合组织瓣,经由皮下隧道转移至鼻翼缺损区,Ⅰ期修复鼻翼缺损的新方法。本组共15例病人,最大面积3.0cm×3.0cm,最小面积1.0cm×1.5cm。结果本组15例病人应用带蒂耳廓复合组织瓣Ⅰ期修复鼻翼缺损,效果良好,色泽和形状均满意。结论应用带蒂的耳廓复合组织瓣可作为Ⅰ期修复鼻翼缺损的首选方法。     

Flip‐avoiding interpolating surface registration for skull reconstruction

Skull reconstruction is an important and challenging task in craniofacial surgery planning, forensic investigation and anthropological studies. Existing methods typically reconstruct approximating surfaces that regard corresponding points on the target skull as soft constraints, thus incurring non‐zero error even for non‐defective parts and high overall reconstruction error. This paper proposes a novel geometric reconstruction method that non‐rigidly registers an interpolating reference surface that regards corresponding target points as hard constraints, thus achieving low reconstruction error. To overcome the shortcoming of interpolating a surface, a flip‐avoiding method is used to detect and exclude conflicting hard constraints that would otherwise cause surface patches to flip and self‐intersect. Comprehensive test results show that our method is more accurate and robust than existing skull reconstruction methods. By incorporating symmetry constraints, it can produce more symmetric and normal results than other methods in reconstructing defective skulls with a large number of defects. It is robust against severe outliers such as radiation artifacts in computed tomography due to dental implants. In addition, test results also show that our method outperforms thin‐plate spline for model resampling, which enables the active shape model to yield more accurate reconstruction results. As the reconstruction accuracy of defective parts varies with the use of different reference models, we also study the implication of reference model selection for skull reconstruction.     

Influence of bone adaptation on tendon‐to‐bone healing in bone tunnel after anterior cruciate ligament reconstruction in a rabbit model

Anterior cruciate ligament (ACL) reconstruction with placement of grafted tendon in bone tunnel is a common surgical procedure. Bone tunnel creation may result in stress shielding of postero‐lateral regions of tibial tunnel. The present study was designed to characterize the changes of peri‐graft bone and compare with tendon‐to‐bone (T‐B) healing in spatial and temporal manners after ACL reconstruction in rabbit. Surgical reconstruction using digital extensor tendon in bone tunnel was performed on 48 rabbits. Twelve rabbits were sacrificed at 0, 2, 6, and 12 weeks postoperatively for radiological and histological examinations. Bone mass and microarchitecture at the anterior, posterior, medial, and lateral regions of tunnel wall at distal femur and proximal tibia were evaluated. Using peripheral quantitative computed tomography, a 26, 22, and 42% decrease in bone mineral density (BMD) relative to baseline was present in the medial region of the femoral tunnel and the posterior and lateral regions of the tibial tunnel, respectively, at week 12 postoperatively (p < 0.05). It was accompanied by a decrease in trabecular number and increase in trabecular spacing, the shift of platelike to rodlike trabeculae, and loss of anisotropy under micro‐computed tomography evaluation. This finding was echoed by histology showing increased osteoclastic activities and poor T‐B healing in these regions. In conclusion, the postoperative bone loss and associated poor T‐B healing was region‐dependent, which may result from adaptive changes after tunnel creation. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1447–1456, 2009     

Local administration of alendronate reduced peri‐tunnel bone loss and promoted graft‐bone tunnel healing with minimal systemic effect on bone in contralateral knee

Continued systemic administration of alendronate was reported to reduce peri‐tunnel bone resorption and promoted graft‐bone tunnel healing at the early stage post‐anterior cruciate ligament (ACL) reconstruction. However, systemic increase in bone mineral density (BMD) in the contralateral intact knee was observed. We tested if single local administration of alendronate into the bone tunnel during ACL reconstruction could achieve similar benefits yet without the systemic effect on bone. Seventy‐two rats with unilateral ACL reconstruction were divided into three groups: saline, low‐dose (6 μg/kg) and mid‐dose (60 μg/kg) alendronate. For local administration, alendronate was applied to the bone tunnels for 2 min before graft insertion and repair. At weeks 2 and 6, the reconstructed complex was harvested for high‐resolution computed tomography (vivaCT) imaging followed by biomechanical test or histology. Our results showed that local administration of low‐dose alendronate showed comparable benefits on the reduction of peri‐tunnel bone loss, enhancement of bone tunnel mineralization, tunnel graft integrity, graft osteointegration and mechanical strength of the reconstructed complex at early stage post‐reconstruction, yet with minimal systemic effect on mineralized tissue at the contralateral intact knee. A single local administration of alendronate at the low‐dose therefore might be used to promote early tunnel graft healing post‐reconstruction. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1897–1906, 2013     

Indian hedgehog signaling and the role of graft tension in tendon‐to‐bone healing: Evaluation in a rat ACL reconstruction model

The structure and composition of the native enthesis is not recapitulated following tendon‐to‐bone repair. Indian Hedgehog (IHH) signaling has recently been shown to be important in enthesis development in a mouse model but no studies have evaluated IHH signaling in a healing model. Fourteen adult male rats underwent ACL reconstruction using a flexor tendon graft. Rats were assigned to two groups based on whether or not they received 0N or 10N of pre‐tension of the graft. Specimens were evaluated at 3 and 6 weeks post‐operatively using immunohistochemistry for three different protein markers of IHH signaling. Quantitative analysis of staining area and intensity using custom software demonstrated that IHH signaling was active in interface tissue formed at the healing tendon‐bone interface. We also found increased staining area and intensity of IHH signaling proteins at 3 weeks in animals that received a pre‐tensioned tendon graft. No significant differences were seen between the 3‐week and 6‐week time points. Our data suggests that the IHH signaling pathway is active during the tendon‐bone healing process and appears to be mechanosensitive, as pre‐tensioning of the graft at the time of surgery resulted in increased IHH signaling at three weeks. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:641–649, 2016.     

Promotion of osteogenesis in tissue‐engineered bone by pre‐seeding endothelial progenitor cells‐derived endothelial cells

In addition to a biocompatible scaffold and an osteogenic cell population, tissue‐engineered bone requires an appropriate vascular bed to overcome the obstacle of nutrient and oxygen transport in the 3D structure. We hypothesized that the addition of endothelial cells (ECs) may improve osteogenesis and prevent necrosis of engineered bone via effective neovascularization. Osteoblasts and ECs were differentiated from bone marrow of BALB/c mice, and their phenotypes were confirmed prior to implantation. Cylindrical porous polycaprolactone (PCL)‐hydroxyapatite (HA) scaffolds were synthesized. ECs were seeded on scaffolds followed by seeding of osteoblasts in the EC‐OB group. In the OB group, scaffolds were only seeded with osteoblasts. The cell‐free scaffolds were denoted as control group. A 0.4‐cm‐long segmental femur defect was established and replaced with the grafts. The grafts were evaluated histologically at 6 weeks postimplantation. In comparison with the OB group, the EC‐OB group resulted in a widely distributed capillary network, osteoid generated by osteoblasts and absent ischemic necroses. Pre‐seeding scaffold with ECs effectively promoted neovascularization in grafts, prevented the ischemic necrosis, and improved osteogenesis. The integration of bone marrow‐derived ECs and osteoblasts in porous scaffold is a useful strategy to achieve engineered bone. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1147–1152, 2008     

Two‐step stem cell therapy improves bone regeneration compared to concentrated bone marrow therapy

Adult stem cells are a promising tool to positively influence bone regeneration. Concentrated bone marrow therapy entails isolating osteoprogenitor cells during surgery with, however, only low cells yield. Two step stem cell therapy requires an additional harvesting procedure but generates high numbers of progenitor cells that facilitate osteogenic pre‐differentiation. To further improve bone regeneration, stem cell therapy can be combined with growth factors from platelet rich plasma (PRP) or its lysate (PL) to potentially fostering vascularization. The aim of this study was to investigate the effects of bone marrow concentrate (BMC), osteogenic pre‐differentiation of mesenchymal stromal cells (MSCs), and PL on bone regeneration and vascularization. Bone marrow from four different healthy human donors was used for either generation of BMC or for isolation of MSCs. Seventy‐two mice were randomized to six groups (Control, PL, BMC, BMC + PL, pre‐differentiated MSCs, pre‐differentiated MSCs + PL). The influence of PL, BMC, and pre‐differentiated MSCs was investigated systematically in a 2 mm femoral bone defect model. After a 6‐week follow‐up, the pre‐differentiated MSCs + PL group showed the highest bone volume, highest grade of histological defect healing and highest number of bridged defects with measurable biomechanical stiffness. Using expanded and osteogenically pre‐differentiated MSCs for treatment of a critical‐size bone defect was favorable with regards to bone regeneration compared to treatment with cells from BMC. The addition of PL alone had no significant influence; therefore the role of PL for bone regeneration remains unclear. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1318–1328, 2019.     

Effect of cavity preparation and bone mineral density on bone‐interface densification and bone‐implant contact during press‐fit implantation of hip stems

Implant loosening and periprosthetic fracture are two major revision causes for uncemented hip stems. The chosen method of cavity preparation could play a key role for both failure mechanisms. The aim of this study was to determine the dependence of the broach type as well as patient bone mineral density (BMD) on densification and contact conditions at the bone‐implant interface. Hip stems were implanted into cadaveric femora using compaction, blunt extraction or sharp extraction broaches with computed tomography scans performed prior to broaching, after broaching and after stem implantation. Proximal periprosthetic bone densification as well as press‐fit, contact area and stem seating relative to the last broach were determined. Median bone densification was higher with the compaction and blunt extraction broaches compared to sharp extraction broaches (181% and 177%, respectively, p = 0.002). The bone densification of femora prepared with compaction broaching increased with higher BMD (R² = 0.183, p = 0.037), while stem seating decreased with higher BMD for all broach types (R² = 0.259, p = 0.001). Incomplete seated prostheses were associated with smaller press‐fit and bone‐implant contact area (R² = 0.249, p = 0.001; R² = 0.287, p < 0.001). Clinical Significance: The results suggest that compaction broaching maximizes bone densification in patients with higher bone density. However, there appears to be an increased risk of insufficient stem seating in high‐density bone that could limit the benefits for primary stability. For lower quality bone, the broach type appears to play a lesser role, but care must be taken to limit extensive stem seating which might increase periprosthetic fracture risk. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1580–1589, 2019.     

Skeletal repair in rabbits using a novel biomimetic composite based on adipose‐derived stem cells encapsulated in collagen I gel with PLGA‐β‐TCP scaffold

In bone tissue engineering, the cell distribution mode in the scaffold may affect in vivo osteogenesis. Therefore, we fabricated a novel biomimetic construct based on a combination of rabbit adipose‐derived stem cells (rASCs) encapsulated in collagen I gel with a PLGA‐β‐TCP scaffold (rASCs‐COL/PLGA‐β‐TCP, group A), the combination of rASCs and PLGA‐β‐TCP (rASCs/PLGA‐β‐TCP, group B), the combination of collagen I gel and PLGA‐β‐TCP (COL/PLGA‐β‐TCP, group C), and PLGA‐β‐TCP scaffold (group D). The composites were implanted into a 15‐mm length critical‐sized segmental radial defect. The results were assessed by histology, radiographs, bone mineral density (BMD), and mechanical testing. After 24 weeks, the medullary cavity recanalized, bone was rebuilt, and molding finished, the bone contour remodeled smoothly and the scaffold degraded completely in group A. The BMDs and mechanical properties were similar to normal. However, the bone defect remained unrepaired in groups B, C, and D. Moreover, the scaffold degradation rate in group A was significantly higher than the other groups. Thus, enhanced in vivo osteogenesis of rASCs wrapped in collagen I gel combined with PLGA‐β‐TCP was achieved, and the bone defect was repaired. We hope this study provides new insights into ASCs‐based bone tissue engineering. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:252–257, 2010     

Interfacial shear strength of bioactive‐coated carbon fiber reinforced polyetheretherketone after in vivo implantation

Despite the excellent osseointegration of carbon‐fiber‐reinforced polyetheretherketone (CFR/PEEK) with a surface hydroxyapatite (HA) coating, the bone‐implant interfacial shear strength of HA‐coated CFR/PEEK after osseointegration is unclear. We examined the interfacial shear strength of HA‐coated CFR/PEEK implants after in vivo implantation in a rabbit femur‐implant pull‐out test model. HA coating was performed by a newly developed method. Uncoated CFR/PEEK, HA‐coated blasted titanium alloy, and uncoated blasted titanium alloy were used as control implants. The implants were inserted into drilled femoral cortex, and pull‐out tests were conducted after 6 and 12 weeks of implantation to determine maximum interfacial shear strength. The HA‐coated CFR/PEEK (15.7 ± 4.5 MPa) and HA‐coated titanium alloy (14.1 ± 6.0 MPa) exhibited significantly larger interfacial shear strengths than the uncoated CFR/PEEK (7.7 ± 1.8 MPa) and the uncoated titanium alloy (7.8 ± 2.1 MPa) at 6 weeks. At 12 weeks, only the uncoated CFR/PEEK (8.3 ± 3.0 MPa) exhibited a significantly smaller interfacial shear strength, as compared to the HA‐coated CFR/PEEK (17.4 ± 3.6 MPa), HA‐coated titanium alloy (14.2 ± 4.8 MPa), and uncoated titanium alloy (15.0 ± 2.6 MPa). Surface analysis of the removed implants revealed detachment of the HA layer in both the HA‐coated CFR/PEEK and titanium alloy implants. The proposed novel HA coating method of CFR/PEEK significantly increased interfacial shear strength between bone and CFR/PEEK. The achieved interfacial shear strength of the HA‐coated CFR/PEEK implant is of the same level as that of grit‐blasted titanium alloy with HA. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1618–1625, 2012