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Biomedical subjects

G W Blunn

Publications and source records attributed to G W Blunn.

At least 19 recordsLinked to original sources

Will mesenchymal stem cells differentiate into osteoblasts on allograft?

Tissue engineering approaches for bone blocks previously have used synthetic scaffolds. Bone graft (allograft) is used to fill bone defects, but standard processing can lessen this scaffold's osteoinductive potential. We wanted to test if allografts could be used to produce a viable bone block using mesenchymal stem cells. We hypothesized that mesenchymal stem cells differentiate into osteoblasts producing extracellular matrix when cultured on allografts. We also hypothesized that the addition of osteogenic supplements would increase the rate of differentiation. To test these hypotheses, mesenchymal stem cells were isolated from bone marrow aspirated from 10 patients and cultured on allografts from five donors (Group 2), producing 50 samples. This was repeated on allografts heat-treated to denature bioactive proteins (Group 1), and repeated again on allografts to which osteogenic supplements (Group 3) were added. Group 2 mesenchymal stem cells differentiated into osteoblasts producing higher levels of alkaline phosphatase, osteopontin, and Type I collagen matrix protein than Group 1. The rate of differentiation of Group 3 mesenchymal stem cells increased with the supplements. Overall, it was established that the bioactive proteins in the allograft stimulated mesenchymal stem cell differentiation into osteoblasts, with production of extracellular matrix, and that this differentiation increased with the addition of osteogenic supplements.

Alkaline Phosphatase↗

Modulation of the soft tissue reactions to percutaneous orthopaedic implants.

To evaluate soft tissue reactions and biofilm formation on percutaneous external fixator screws coated with diamond-like carbon (DLC) and hydroxyapatite (HA) coatings on stainless-steel (SS) pins in an ovine loaded osteotomy model, an Orthofix external fixator was used to stabilize a 3-mm tibial midshaft osteotomy with six tapered pins inserted into the right tibia of 32 skeletally mature Friesland ewes. Animals were divided into four groups; SS, fully coated HA, DLC, and HA-coated threads. At 10 weeks, specimens were harvested and the pins were removed en bloc to examine the interfaces between the surface coatings and the tissues. Fully coated HA pins had a significantly higher percentage of dermal contact with the pin surface than HA-coated threads (p=0.028). The presence of a biofilm was evident on all pin surfaces except DLC-coated pins. Significantly greater numbers of bacteria were present on fully coated HA and plain stainless-steel pins compared with DLC. The surface of DLC-coated pins had a significantly lower number of bacterial colonies compared to SS (p=0.028) and fully coated HA pins (p=0.005). Fully coated HA pins have greater dermal attachment to the pin surface than the other pin coatings investigated. DLC-coated pins have the potential to prevent biofilm formation and bacterial colonization that may reduce infection and consequent pin loosening. An external fixator pin that is partially coated with HA to encourage bone and soft tissue integration and with DLC to reduce biofilm formation is advocated.

Animals↗

Nature's answer to breaching the skin barrier: an innovative development for amputees.

The human body has evolved to maintain homeostasis through the covering of skin and mucous membranes, which separate the internal environment from the harsh and variable external milieu. Few structures naturally penetrate these coverings, and teeth are the only exception in human beings. Attempts to breach these barriers, to develop skin- penetrating, bone-anchored amputation prostheses, can lead to opportunist invasion by microorganisms and subsequent infection, which can jeopardize the life of the individual. There are only a few fascinating examples where the integument of other species is interrupted without such dire consequences, and the deer antler is one such case. Deer antlers are cephalic bony appendages arising from the frontal bones of the skull of the males of most deer species, and are true transient skin-penetrating structures. Antlers are subject to extreme loading during the rutting season and yet the skin-bone barrier remains intact. Here we show how deer antlers can be used as natural analogues for the successful development of specialized orthopaedic amputation prosthetics. We have used quantitative and qualitative findings from a study of the morphology of deer antlers to develop a device that mimics their structure, which creates a tight seal between the implant and the host tissues, for use in amputation prosthetics.

Amputation, Surgical↗

Validation of the soft tissue restraints in a force-controlled knee simulator.

In vitro testing of total knee replacements (TKRs) is important both at the design stage and after the production of the final components. It can predict long-term in vivo wear of TKRs. The two philosophies for knee testing are to drive the motion by displacement or to drive the motion by force. Both methods have advantages and disadvantages. For force control an accurate simulation of soft tissue restraints is required. This study was devised to assess the accuracy of the soft tissue restraints of the force-controlled Stanmore knee simulator in simulating the restraining forces of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL). In order to do this, human cadaver knee joints were subjected to the ISO Standard Walking Cycle. The resulting kinematics were monitored when the soft tissue structures were intact, when the ACL and PCL were resected, and when they were simulated by springs positioned anteriorly and posteriorly. The stiffness of the springs was determined from the literature. Two different stiffnesses of springs were used which were 7.24 N/mm (designated as soft springs) and 33.8 N/mm (designated as hard springs). All the intact knees showed displacements that were within the range of the machine. Cutting the ACL and PCL resulted in anterior and posterior motion and internal external rotation that were significantly greater than the intact knee. Results showed that when the ACL and PCL were cut hard springs positioned anterior and posterior to the knee returned the knee to near normal anterior-posterior (AP) motion. Using hard springs in the posterior position in any condition reduced rotational displacements. Therefore using springs in a force-controlled simulator is a compromise. More accuracy may be obtained using springs that are of intermediate stiffness.

Cadaver↗

The novel use of resorbable Vicryl mesh for in vivo tendon reconstruction to a metal prosthesis.

We examined the mechanical properties of Vicryl (polyglactin 910) mesh in vitro and assessed its use in vivo as a novel biomaterial to attach tendon to a hydroxyapatite-coated metal implant, the interface of which was augmented with autogenous bone and marrow graft. This was compared with tendon re-attachment using a compressive clamp device in an identical animal model. Two- and four-ply sleeves of Vicryl mesh tested to failure under tension reached 5.13% and 28.35% of the normal ovine patellar tendon, respectively. Four-ply sleeves supported gait in an ovine model with 67.05% weight-bearing through the operated limb at 12 weeks, without evidence of mechanical failure. Mesh fibres were visible at six weeks but had been completely resorbed by 12 weeks, with no evidence of chronic inflammation. The tendon-implant neoenthesis was predominantly an indirect type, with tendon attached to the bone-hydroxyapatite surface by perforating collagen fibres.

Animals↗

Extensor mechanism reconstruction after proximal tibial replacement.

We developed an in vivo model of the attachment of a patellar tendon to a metal implant to simulate the reconstruction of an extensor mechanism after replacement of the proximal tibia. In 24 ewes, the patellar tendon was attached to a hydroxyapatite (HA)-coated titanium prosthesis. In 12, the interface was augmented with autograft containing cancellous bone and marrow. In the remaining ewes, the interface was not grafted. Kinematic gait analysis showed nearly normal function of the joint by 12 weeks. Force-plate assessment showed a significant increase in functional weight-bearing in the grafted animals (p = 0.043). The tendon-implant interface showed that without graft, encapsulation of fibrous tissue occurred. With autograft, a developing tendon-bone-HA-implant interface was observed at six weeks and by 12 weeks a layered tendon-fibrocartilage-bone interface was seen which was similar to a direct-type enthesis. With stable mechanical fixation, an appropriate bioactive surface and biological augmentation the development of a functional tendon-implant interface can be achieved.

Animals↗

Analysis of glenoid fixation for a reversed anatomy fixed-fulcrum shoulder replacement.

The restoration of pain-free stable function in gleno-humeral arthritic cases in various situations such as rotator cuff deficiency, old trauma and failed total shoulder arthroplasty is a challenging clinical dilemma. The Bayley-Walker shoulder has been designed specifically for very difficult cases where surface replacement devices do not provide sufficient stability. This device is a fixed-fulcrum reverse anatomy implant where the centre of rotation is placed medially and distally with respect to the normal shoulder, to increase the lever arm of the abductor muscles. An important problem in devices of this type is obtaining secure and long-lasting fixation of the glenoid component. In this design, fixation is achieved using a tapered screw for engagement with cortical bone and HA coating for subsequent osseointegration. This study presents the results from a three-dimensional finite element analysis conducted on this component for two load cases at 60 degrees and 90 degrees abduction. The results showed that most of the forces were transmitted from the component to the cortical bone of the scapula, the remaining load being transmitted through cancellous bone. Histology from a retrieved case shows evidence of bone remodelling. The retrieval case obtained some time after implantation showed new bone formation had occurred around the threads onto the HA coating. Fixing the component in this way at multiple locations in cortical bone may overcome the problems of glenoid loosening historically associated with cemented constrained devices.

Arthroplasty, Replacement↗

A histomorphological study of tendon reconstruction to a hydroxyapatite-coated implant: regeneration of a neo-enthesis in vivo.

The attachment of tendons and ligaments to massive endoprostheses remains a clinical challenge due to the difficulty in achieving a soft tissue implant interface with a mechanical strength sufficient to transmit the forces necessary for locomotion. We have used an in vivo animal model to study patellar tendon attachment to an implant surface. The interface generated when the patellar tendon was attached to a hydroxyapatite (HA) coated implant was examined using light microscopy and a quantitative histomorphological analysis was performed. In the Autograft Group, the interface was augmented with autogenous cancellous bone and marrow graft, and at six weeks an indirect-like insertion was observed. At twelve weeks, the interface was observed to be a layered neo-enthesis, whose morphology was similar to a normal direct tendon insertion. In the HA Group, the tendon-implant interface was not augmented, and the implant was enveloped by a dense collagenous fibrous tissue. This study shows that a tendon-implant neo-enthesis can develop in situ by employing a suitable implant surface in association with biological augmentation.

Animals↗

Glass ionomer as an expander of allograft in revision arthroplasty of the hip.

The use of glass ionomer as a bone graft expander was investigated in an in vivo model of revision hip arthroplasty. Bone grafts of pure allograft and allograft + glass ionomer particles in a 50:50 by weight mixture were implanted in an ovine hemi-arthroplasty model. Post-operative assessments of locomotor function, radiographic appearance and quantitative changes in mineralisation around the graft were made at 2, 4 and 6 months. Post-mortem assessments of radiographic and histologic appearance of the grafts were made at 6 months. No significant differences were noted in any of the measured or assessed parameters between the two graft types. The glass ionomer particles seemed to be well tolerated within the matrix of new bone, smaller sized particles appearing to be better incorporated than larger ones. The use of particles of glass ionomer as a bone graft expander, in this in vivo model of revision hip arthroplasty, would therefore appear to offer no detriment in performance over pure allograft in the short to medium term.

Acrylic Resins↗

Polyethylene wear characteristics in vivo and in a knee stimulator.

Validation of a wear simulator requires that the device produce a similar type and amount of wear and particles of a comparable morphology as occurs clinically. Using techniques previously established to compare polyethylene particles from hip simulators to those from retrieved tissues, particles isolated from six revised posterior stabilized knee replacements were characterized and compared to particles generated from the same knee design worn in a knee simulator. The particles produced in the knee simulator were of comparable size but had less variability in their form factor compared to the particles produced in vivo. Comparable wear features were seen on the articulating surfaces in both groups. These results indicate that this knee joint simulator is able to reproduce a baseline type of wear that is similar to that in vivo and should encourage further use of this device to better understand knee component wear and function.

Arthroplasty, Replacement, Knee↗

A comparison of bone remodelling around hydroxyapatite-coated, porous-coated and grit-blasted hip replacements retrieved at post-mortem.

We investigated the implant-bone interface around one design of femoral stem, proximally coated with either a plasma-sprayed porous coating (plain porous) or a hydroxyapatite porous coating (porous HA), or which had been grit-blasted (Interlok). Of 165 patients implanted with a Bimetric hip hemiarthroplasty (Biomet, Bridgend, UK) specimens were retrieved from 58 at post-mortem. We estimated ingrowth and attachment of bone to the surface of the implant in 21 of these, eight plain porous, seven porous HA and six Interlok, using image analysis and light morphometric techniques. The amount of HA coating was also quantified. There was significantly more ingrowth (p = 0.012) and attachment of bone (p < 0.05) to the porous HA surface (mean bone ingrowth 29.093 +/- 2.019%; mean bone attachment 37.287 +/- 2.489%) than to the plain porous surface (mean bone ingrowth 21.762 +/- 2.068%; mean bone attachment 18.9411 +/- 1.971%). There was no significant difference in attachment between the plain porous and Interlok surfaces. Bone grew more evenly over the surface of the HA coating whereas on the porous surface, bone ingrowth and attachment occurred more on the distal and medial parts of the coated surface. No significant differences in the volume of HA were found with the passage of time. This study shows that HA coating increases the amount of ingrowth and attachment of bone and leads to a more even distribution of bone over the surface of the implant. This may have implications in reducing stress shielding and limiting osteolysis induced by wear particles.

Aged↗

Plate fixation of prostheses after segmental resection for bone tumours.

This study investigated the concept of using plates to attach endoprostheses to bone after segmental resection for bone tumours in an animal model. Titanium alloy plates integrated with the prosthesis and coated with hydroxyapatite were attached to bone by screws. This type of uncemented fixation relied on the induction of periosteal bone formation into and around the plates to secure the implant to bone. Two, three, and six-slotted plate designs were investigated. On retrieval, each plate was securely fixed by new bone. Bone apposition on the external surface of the plates occurred through a combination of periosteal bone production, invasion of bone through slots in the plate, and bone growth over the ends of the plates. Most plates became incorporated into a remodelled cortex. Higher bone turnover rates (microm day(-1)) were seen in bone in the slots of the plate compared with normal cortical bone turnover (p < 0.05). Significantly higher rates of turnover were measured beneath slotted parts of the plates compared with regions below the unslotted parts (p < 0.05). The cross-sectional area of bone surrounding the six-plate implant design was significantly higher than that of the three-plate (p < 0.05) and two-plate (p < 0.05) designs. In addition, significantly more bone formed adjacent to the six-plated implant design compared with that in the contralateral limb (p = 0.002). However, no significant difference was found when the total cortical area around the three-plated design was compared with that of the contralateral limb (p = 0.63). In contrast, significantly less bone was measured adjacent to the two-plate design than in the untreated limb (p = 0.001). Image analysis also demonstrated increased cortical porosity adjacent to the six-plate design compared with the three-plate (p = 0.004) and two-plate (p < 0.05) designs. Finite element analysis demonstrated that the six and three-plate designs increased the second moment of area compared with that in the left tibia (p = 0.003 and 0.066, respectively). However, the attachment of the more flexible two-plate design did not significantly increase the second moment of area compared with that in the contralateral limb (p = 0.235). It was concluded that due to both mechanical and biological effects, the hydroxyapatite-coated plate designs generated new bone that enhanced fixation and encouraged plate integration into the load-bearing structure of the cortex. This method of fixation may be an alternative to the use of intramedullary cemented stems in patients requiring bone tumour implants and may be the only way to preserve the joint in difficult cases where only short segments of bone remain.

Animals↗

Fractographic examination of racing greyhound central (navicular) tarsal bone failure surfaces using scanning electron microscopy.

The greyhound is a fatigue fracture model of a short distance running athlete. Greyhounds have a high incidence of central (navicular) tarsal bone (CTB) fractures, which are not associated with overt trauma. We wished to determine whether these fractures occur because of accumulation of fatigue microdamage. We hypothesized that bone from racing dogs would show site-specific microdamage accumulation, causing predisposition to structural failure. We performed a fractographic examination of failure surfaces from fractured bones using scanning electron microscopy and assessed microcracking observed at the failure surface using a visual analog scale. Branching arrays of microcracks were seen in failure surfaces of CTB and adjacent tarsal bones, suggestive of compressive fatigue failure. Branching arrays of microcracks were particularly prevalent in remodeled trabecular bone that had become compact. CTB fractures showed increased microdamage when compared with other in vivo fractures (adjacent tarsal bone and long bone fractures), and ex vivo tarsal fractures induced by monotonic loading (P < 0.02). It was concluded that greyhound racing and training often results in CTB structural failure, because of accumulation and coalescence of branching arrays of fatigue microcracks, the formation of which appears to be predisposed to adapted bone.

Adaptation, Physiological↗

Prevention of loosening in total hip replacements using guided bone regeneration.

The aim of this study was to prevent wear debris from reaching the interface of the acetabular cup and femoral component by using a partially occlusive expanded polytetrafluoroethylene membrane. This membrane initially acted as a physical seal, which became incorporated by bone and soft tissue, forming a secondary biologic seal, preventing loosening. An animal model was developed to test the hypothesis. The model replicated the mechanisms of loosening where the effects of wear debris were studied. Using femoral heads with the appropriate roughness, a goat model produced the radiologic and histologic presentation of loosening as observed in total hip replacements in humans. Loosening was assessed by measurement of the radiolucent lines, and was attributed to wear debris by histologic investigation. The expanded polytetrafluoroethylene membrane prevented acetabular implant loosening to a statistical significance of 0.02 in a blinded assessment when compared with the control groups. Loosening of the first 5 mm of the proximomedial aspect of the femur also was prevented. The authors of the current study prevented wear particle-induced osteolysis in the acetabular component by using an expanded polytetrafluoroethylene membrane to seal the bone-cement interface.

Animals↗

Cementless fixation for primary segmental bone tumor endoprostheses.

To combat the high incidence of aseptic loosening for young patients and for patients with failed implants after resection for bone tumors, intramedullary cementless fixation of massive tumor implants was investigated. These implants consist of a hydroxyapatite coated titanium stem. To date, 47 of these prostheses have been inserted for the treatment of primary bone tumors. Radiographs indicate that the stems are osseointegrated. Radiolucent lines have not been seen between the implant and the bone. Bone remodeling changes have been observed. In several cases in which the implant was not seated properly on the transaction site, bone grew to the shoulder of the implant. Bone remodeling was particularly evident in stems that were coated over their entire surface. In these cases, the implant induced local bone resorption so that the bone around the midstream region became thinner, with resorption of cortical bone on the periosteal surface and maintenance of bone on the endosteal surface adjacent to the stem. This effect was attributed to stress shielding, and a three-dimensional finite element model using loading data obtained from a telemetry study indicated that, where the stem was bonded to the bone over the entire surface, stresses in the outer cortex became reduced. In the finite element model, reducing the region of hydroxyapatite coating to approximately 1/3 of the stem length reduced the extent of the low-stress area in the outer cortex. Subsequently, prostheses have been coated with hydroxyapatite over only approximately 1/3 of their stem. This method of fixing the massive endoprosthesis to the bone is thought to be successful in the short-term and offers an alternative to cemented fixation.

Bone Neoplasms↗

Methodology for long-term wear testing of total knee replacements.

This article begins to address the validation requirements of wear testing on total knee replacements in a knee simulator. The knee simulator has four stations. The axial force is variable but reaches a maximum of 2.3 kN. Physiologic anteroposterior shear force and rotational torques are supplied to the knee. The forces and displacements are timed to coincide with those of a typical gait cycle. Kinematics of the simulator are dependent on the type of knee being tested. Tests of designs with well known clinical histories were done to 10 million cycles. The relative amounts and types of wear shown by the designs were similar to that found in their clinical histories. Wear tracks on more conforming designs were larger, and the penetration into the plastic appeared to be less. This did not necessarily mean that wear, as measured by loss of material, was reduced on conforming designs. Delamination of the plastic was achieved only after aging the tibial components. Wear particles isolated from the lubricating fluid were similar in size and shape to those isolated from in vivo specimens. However, the relative amounts of wear particle shapes were different depending on the design. At the start of the tests, all of the flexibly mounted tibial components showed more motion than after 5 million cycles, indicating that the surface of the plastic became more conforming. This study showed that knee wear similar to wear observed in vivo can be reproduced in the laboratory. The parameters and methods elucidated in this introductory study should form the basis for use in preclinical wear tests of total knee replacements.

Biomechanical Phenomena↗

Evaluation of a testing method for the fatigue performance of total knee tibial trays.

Catastrophic failure of tibial baseplates due to fatigue fracture have occurred in patients. The International Standards Organisation (ISO) have proposed an endurance test to ensure a safety level for trays with respect to this problem. At present the magnitude of the applied load has not been defined. The purpose of this study is to evaluate the ISO test by comparing the results of two tibial trays: one with a clinical history of fracture of the tibial baseplate in some cases (Kinematic) and one without such a record (Kinemax). A load of 2000 N was selected, representing the peak force during the normal walking cycle. Finite element analysis (FEA) predicted that both the Kinematic and Kinemax trays would rapidly fail for two defined contact positions. Mechanical testing performed on both these components confirmed the FEA predictions. However, under service conditions, the Kinematic tray has been reported to have a failure of only 1-2%, the failure occurring at a mean of 54 months for early fracture and 7 years for late fracture. There are no published reports of failed Kinemax trays. It is concluded that the ISO test is an exaggeration of reality when a physiological load is used. As a result of our study we propose that a load of 500 N would effectively screen components with respect to the ISO test conditions for the likelihood of fracture.

Bone Plates↗