Matthew H. Pelletier

Can platelet-rich plasma (PRP) improve bone healing? A comparison between the theory and experimental outcomes

The increased concentration of platelets within platelet-rich plasma (PRP) provides a vehicle to deliver supra-physiologic concentrations of growth factors to an injury site, possibly accelerating or otherwise improving connective tissue regeneration. This potential benefit has led to the application of PRP in several applications; however, inconsistent results have limited widespread adoption in bone healing. This review provides a core understanding of the bone healing mechanisms, and corresponds this to the factors present in PRP. In addition, the current state of the art of PRP preparation, the key aspects that may influence its effectiveness, and treatment outcomes as they relate specifically to bone defect healing are presented. Although PRP does have a sound scientific basis, its use for bone healing appears only beneficial when used in combination with osteoconductive scaffolds; however, neither allograft nor autograft appear to be appropriate carriers. Aggressive processing techniques and very high concentrations of PRP may not improve healing outcomes. Moreover, many other variables exist in PRP preparation and use that influence its efficacy; the effect of these variables should be understood when considering PRP use. This review includes the essentials of what has been established, what is currently missing in the literature, and recommendations for future directions.

Spine Interbody Implants: Material Selection and Modification, Functionalization and Bioactivation of Surfaces to Improve Osseointegration

The clinical outcome of lumbar spinal fusion is correlated with achievement of bony fusion. Improving interbody implant bone on‐growth and in‐growth may enhance fusion, limiting pseudoarthrosis, stress shielding, subsidence and implant failure. Polyetheretherketone (PEEK) and titanium (Ti) are commonly selected for interbody spacer construction. Although these materials have desirable biocompatibility and mechanical properties, they require further modification to support osseointegration. Reports of extensive research on this topic are available in biomaterial‐centric published reports; however, there are few clinical studies concerning surface modification of interbody spinal implants. The current article focuses on surface modifications aimed at fostering osseointegration from a clinicians point of view. Surface modification of Ti by creating rougher surfaces, modifying its surface topography (macro and nano), physical and chemical treatment and creating a porous material with high interconnectivity can improve its osseointegrative potential and bioactivity. Coating the surface with osteoconductive materials like hydroxyapatite (HA) can improve osseointegration. Because PEEK spacers are relatively inert, creating a composite by adding Ti or osteoconductive materials like HA can improve osseointegration. In addition, PEEK may be coated with Ti, effectively bio‐activating the coating.

The Compressive Properties of Bone Cements Containing Large Doses of Antibiotics

The addition of large amounts of antibiotics to bone cement provides a convenient local delivery, but may influence the compressive properties of the cement. Flucloxacillin and vancomycin were added to Simplex P (Stryker, Limerick, Ireland) and VersaBond (Smith & Nephew) cements. Tripling the antibiotic dose from 2 to 6 g had little effect on the static compressive properties 24 hours after curing. After 4 weeks in phosphate-buffered saline, there was marked decrease in properties with the addition of antibiotics. Compressive strength of cements with 6 g of antibiotic was reduced to near or below the ASTM and ISO minimum of 70 MPa after 4 weeks in phosphate-buffered saline. Microcomputer tomography revealed increased porosity and clumping of the radiopacifier with the addition of antibiotics.

The design evolution of interbody cages in anterior cervical discectomy and fusion: a systematic review

BackgroundAnterior cervical discectomy with fusion is a common surgical procedure for patients experiencing pain and/or neurological deficits due to cervical spondylosis. Although iliac crest bone graft remains the gold standard today, the associated morbidity has inspired the search for alternatives, including allograft, synthetic and factor/cell-based grafts; and has further led to a focus on cage fusion technology. Compared to their graft counterparts, cage interbody implants have enhanced biomechanical properties, with designs constantly improving to maximise biocompatibility and osseointegration. We present a systematic review examining the historical progress of implant designs and performance, as well as an update on the currently available designs, and the potential future of cervical interbody implants.MethodsWe performed a systematic review using the keywords “cervical fusion implant design”, with no limits on year of publication. Databases used were PubMed, Medline, Embase and Cochrane. In addition, the search was extended to the reference lists of selected articles.Results180 articles were reviewed and 64 articles were eligible for inclusion. Exclusion criteria were based around study design, implant information and patient cohorts. The evolution of cage implant design has been shaped by improved understanding of ideal anatomy, progress in materials research and continuing experimentation of structural design. Originally, designs varied primarily in their choice of structure, however long-term studies have displayed the overall advantages of non-threaded, wedge shaped cages in complementing healthy anatomical profiles, and thus focus has shifted to refining material utilisation and streamlining anterior fixation.ConclusionsEvolution of design has been dramatic over the past decades; however an ideal cage design has yet to be realised. Current research is focusing on the promotion of osseointegration through bioactiviation of surface materials, as well as streamlining anterior fixation with the introduction of integrated screws and zero profile designs. Future designs will benefit from a combination of these advances in order to achieve ideal disc heights, cervical alignments and fusions.

Platelet function and constituents of platelet rich plasma.

Platelet Rich Plasma (PRP) therapies require blood to be processed prior to application, however, the full assessment of the output of platelet sequestration devices is lacking. In this study the products of the Autologous Fluid Concentrator (Circle BiologicsTM, Minneapolis, MN) and the Gravitational Platelet Separation System (GPS, Biomet, Warsaw, IN, USA) were evaluated in terms of platelet viability and PRP constituents. The AFC and GPS produced 6.4 (±1.0) ml and 6.3 (±0.4) ml of PRP, with platelet recovery of 46.4% (±14.7%) and 59.8% (±24.2%) producing fold increases of platelets of 4.19 (±1.62) and 5.19 (±1.62), respectively. Fibrinogen concentration was increased above baseline PPP produced with the AFC. pH was lower for both of the processed samples than for whole blood. White Blood Cell count was increased around 5 fold. Functional tests showed preserved viability with both devices. This represents essential knowledge that every treating physician should have before they can confidently administer PRP therapy produced by any method. These are the first published results of platelet function for the GPS system and the first performance results of the AFC system. The PRP produced is classified according to broad classifications as Leukocyte-PRP (L-PRP) for both devices.

Acromioclavicular reconstructions with hamstring tendon grafts: A comparative biomechanical study

The surgical treatment of chronic acromioclavicular injuries remains controversial. There is increasing use of autogenous tendon grafts to perform these reconstructions. This study examined the mechanical properties of differing configurations of these grafts. Mechanical testing of acromioclavicular joint reconstructions was performed with a screw and soft tissue washer for tendon fixation, a simple loop of tendon tied to itself, and a bio-interference screw for tendon fixation, with and without a loop of nonabsorbable suture for reinforcement. The bio-interference screw fixation, with reinforcement by a loop of nonabsorbable suture, gave the highest load to failure among the group (502N +/- 177), which was not significantly different from the intact ligaments (705 N +/- 132), although it was significantly less stiff than the intact group (57.2 N/mm +/- 12.6 and 109.7 N/mm +/- 32.6, respectively). All other reconstructions had an ultimate load and stiffness which were significantly less than that of the intact specimens.

Platelet-rich plasma and bone defect healing.

On activation, platelets secrete an array of growth factors that contribute to bone regeneration. Combining platelet-rich plasma (PRP) with bone graft substitutes has the potential to reduce or replace the reliance on autografts. Lack of standardization and improper use may contribute to the conflicting outcomes reported within both preclinical and clinical investigations using PRP. This study investigates the effect of PRP dose on bone augmentation. Eighty critical-sized defects were created in the cancellous bone of the medial proximal tibia and the distal femur of 20 five-year-old female sheep. The defects were treated with three doses of an autologous thrombin-activated PRP combined with a biphasic calcium phosphate (BCP) or autograft and empty defects. Radiography, micro-computed tomography, histology, histomorphometry, and fluorochrome bone labels were examined at 4 weeks. The empty defects did not spontaneously heal. The highest dose of PRP treatment had a significantly greater micro-CT bone volume/total volume compared with the BCP alone (PRP: 30.6%±1.8%; BCP: 24.5%±0.1%). All doses of PRP treatment were significantly greater than the BCP alone for histomorphometric new bone area (PRP: 14.5%±1.3%; BCP: 9.7%±1.5%) and bone ingrowth depth (PRP: 2288±210 μm; BCP:1151±268 μm). From week 2 onward, PRP had a significant effect on the weekly bone ingrowth compared with BCP; however, autografts had the highest amount of weekly fluorescent bone labeling. PRP induces new bone formation with a dose-dependent response at 4 weeks when used with a BCP in sheep.

PEEK Versus Ti Interbody Fusion Devices: Resultant Fusion, Bone Apposition, Initial and 26-Week Biomechanics.

Study Design:Comparative evaluation of in vitro and in vivo biomechanics, resulting fusion and histomorphometric aspects of polyetheretherketone (PEEK) versus titanium (Ti) interbody fusion devices in an animal model with similar volumes of bone graft. Objective:Identify differences in the characteristics of fusion and biomechanics immediately following implantation (time 0) and at 26 weeks with each interbody implant. Summary of Background Data:PEEK has been well accepted in spinal surgery, it provides a closer match to the mechanical properties of bone than metallic implants such as Ti. This is thought to reduce graft stress shielding and subsidence of interbody fusion devices. There remains controversy as to the overall influence of this as a factor influencing resultant fusion and initial stability. Although material modulus is 1 factor of importance, other design factors are likely to play a large role determining overall performance of an interbody implant. Methods:A Ti and PEEK device of similar size with a central void to accommodate graft material were compared. The PEEK device had a ridged surface on the caudal and cephalad surfaces, whereas Ti device allowed axial compliance and had bone ingrowth endplates and polished internal surfaces. A 2-level ALIF was performed in 9 sheep and fusion, biomechanics, and bone apposition were evaluated at 26 weeks. Time 0 in vitro biomechanical tests were performed to establish initial stability immediately after implantation. Results:No differences were detected in the biomechanical measures of each of the devices in in vitro time 0 tests. All levels were fused by 26 weeks with considerably lower range of motion when compared with in vitro tests. Range of motion in all modes of bending was reduced by over 70% when compared with intact values for axial rotation (Ti-74%, PEEK-71%), lateral bending (Ti-90%, PEEK-88%), and flexion/extension (Ti-92%, PEEK-91%). Mechanical properties of fusions formed with each implant did not differ; however, bone apposition was variable with polished internal Ti surfaces being lower than PEEK and treated Ti endplates showing the greatest levels. Graft material displayed axial trabecular alignment with both implants. Conclusions:Although material properties and surface characteristics resulted in differing amounts of biological integration from the host, both implants were capable of producing excellent fusion results using similar volumes of bone graft.

Photoelastic comparison of strains in the underlying glenoid with metal-backed and all-polyethylene implants

An alteration in the stress and strain environment following arthroplasty is believed to lead to bone remodeling, which can trigger implant loosening and subsequent failure. Bone remodeling, while well-studied in hip arthroplasty, has received less attention in total shoulder replacement. This study examines differences in strain states between intact glenoids and following replacement with an uncemented metal backed keeled component and a cemented all polyethylene pegged component with the same articular geometry, using the photoelastic method. Strain measurements were taken in glenoids before and after implantation under 4 loading conditions corresponding to 4 abduction angles: 0 degrees, 30 degrees, 60 degrees, and 90 degrees. Shear strains increased at most locations following reconstruction with both of the implants. Uncemented, keeled metal backed implants produced areas of higher cortical shear strains compared to cemented, all PE pegged implants.

The effect of gamma irradiation on the anisotropy of bovine cortical bone

Bone is an anisotropic non-homogenous composite material composed of inorganic bone mineral embedded in an organic matrix. The mechanical behaviour of bone is governed by the volume fraction of these constituents, their mechanical properties, the degree of crystallite-collagen orientation and the bonding between phases. This study aims to evaluate the mechanical role of these constituents in the expression of anisotropy by using gamma irradiation to alter the mineralised collagen fibrils. Bovine cortical cubes were prepared, treated and mechanically tested in uniaxial compression in the axial, radial and tangential orientations. Ultimate stress, ultimate strain, energy to failure and stiffness were evaluated. This study confirmed deleterious effect of gamma irradiation on the axial compressive properties of cortical bone with a dose dependent decrease in ultimate stress of 6% (P=0.231) and 16% (P=0.001) at 15 and 25 kGy respectively. This corresponded to a 39% (P=0.058) and 30% (P=0.167) reduction in energy to failure. In the radial orientation there was also a dose dependant decrease in ultimate stress which was consistent with a statistically significant decline in ultimate strain (31% (P=0.003) and 36% (P=0.000)) and energy to failure (36% (P=0.053) and 45% (P=0.008)) at both doses. In the tangential orientation there was a significant 22% (P=0.01) and 23% (P=0.02) decrease in stiffness; though these changes did not alter ultimate stress considerably. This study provides valuable insights into the role of collagen in the radial and tangential orientation when loaded in compression; while also building on the body of work related to the use of gamma irradiation for load bearing bone allografts.