Joseph Alsousou

The biology of platelet-rich plasma and its application in trauma and orthopaedic surgery: a review of the literature.

Although mechanical stabilisation has been a hallmark of orthopaedic surgical management, orthobiologics are now playing an increasing role. Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline. The platelet alpha granules are rich in growth factors that play an essential role in tissue healing, such as transforming growth factor-beta, vascular endothelial growth factor, and platelet-derived growth factor. PRP is used in various surgical fields to enhance bone and soft-tissue healing by placing supraphysiological concentrations of autologous platelets at the site of tissue damage. The easily obtainable PRP and its possible beneficial outcome hold promise for new regenerative treatment approaches. The aim of this literature review was to describe the bioactivities of PRP, to elucidate the different techniques for PRP preparation, to review animal and human studies, to evaluate the evidence regarding the use of PRP in trauma and orthopaedic surgery, to clarify risks, and to provide guidance for future research.

The role of platelet-rich plasma in tissue regeneration.

Platelet-rich plasma (PRP), an autologous derivative of whole blood that contains a supraphysiological concentration of platelets, has gained increasing attention in both the scientific literature and the wider media for its potential application in the treatment of traumatic musculoskeletal injury. The theoretical benefit of PRP in providing a local environment for tissue regeneration which is rich in growth factors and other cytokines has been supported by in vitro and animal studies which suggest a positive influence on the migration and proliferation of a number of cell types. However, the reported clinical use of PRP is largely confined to the last two decades and initially centred around its application in dental and maxillofacial surgery. More recently, developments in research of the regenerative effects of PRP in a range of tissue types including bone, cartilage, tendon and muscle, particularly in the context of traumatic injury, have attracted interest in fields such as orthopaedic and plastic surgery where effective union of sometimes poorly vascularised and damaged tissue is a critical determinant of successful clinical outcome. Despite the lack of high-quality trial data, results from clinical studies have been encouraging, and PRP administration remains an attractive strategy given its cost-effective and minimally invasive nature. In this review, we summarise the current literature on the use of PRP and highlight areas of controversy and emerging clinical applications.

The cost and consequences of proximal femoral fractures which require further surgery following initial fixation

We evaluated the cost and consequences of proximal femoral fractures requiring further surgery because of complications. The data were collected prospectively in a standard manner from all patients with a proximal femoral fracture presenting to the trauma unit at the John Radcliffe Hospital over a five-year period. The total cost of treatment for each patient was calculated by separating it into its various components. The risk factors for the complications that arose, the location of their discharge and the mortality rates for these patients were compared to those of a matched control group. There were 2360 proximal femoral fractures in 2257 patients, of which 144 (6.1%) required further surgery. The mean cost of treatment in patients with complications was £18,709 (£2606.30 to £60,827.10), compared with £8610 (£918.54 to £45,601.30) for uncomplicated cases (p < 0.01), with a mean length of stay of 62.8 (44.5 to 79.3) and 32.7 (23.8 to 35.0) days, respectively. The probability of mortality after one month in these cases was significantly higher than in the control group, with a mean survival of 209 days, compared with 496 days for the controls. Patients with complications were statistically less likely to return to their own home (p < 0.01). Greater awareness and understanding are required to minimise the complications of proximal femoral fractures and consequently their cost.

The AutoQual ultrasound elastography method for quantitative assessment of lateral strain in post-rupture Achilles tendons

This paper presents the AutoQual elastography method: a novel algorithm that improves the quality of 2D displacement field calculation from ultrasound radio frequency (RF) sequences of acutely ruptured Achilles tendons to determine image-lateral strain fields and has potential use for ligaments and muscles. This method uses 2D bicubic spline interpolation of the RF signal, Quality Determined Search, Automatic Search Range and Adaptive Block Size components as a novel combination that is designed to improve continuity and decrease displacement field noise, especially in areas of low signal strength. We present a simple experiment for quantitatively comparing the AutoQual method to a multiscale (MS) elastography method from ultrasound RF sequences of a 5% agar phantom for rigid body motion and known lateral strain loads with speeds up to 5mm/s. We finally present examples of four in vivo Achilles tendons in various damage states and with manual or artificially controlled passive flexion of the foot. Results show that the AutoQual method offers a substantial improvement on the MS method, achieving similar performance for rigid body tracking at all speeds, a lower normalized square error at all strains induced and a more continuous strain field at higher compression rates. AutoQual also showed a greater average normalized cross correlation for image blocks in the area of interest, a lower standard deviation of the strain field and a visually more acceptable point tracking for in vivo examples. This work demonstrates lateral ultrasound elastography which is robust to the complex passive motion of the Achilles and to various imaging artifacts associated with imaging tendon rupture. This method potentially has a wide clinical application for assessing in vivo strains in and hence mechanical function of any near skin surface tissues that are longitudinally loaded.

Effect of platelet-rich plasma on healing tissues in acute ruptured Achilles tendon: a human immunohistochemistry study.

BACKGROUND Platelet-rich plasma (PRP), an autologous derivative of whole blood that contains a supraphysiological concentration of platelets, is thought to invoke an earlier and improved tissue healing response. This notion has been supported by in-vitro and animal studies in bone, cartilage, tendon, and muscle. To our knowledge no published study exists of the effects of PRP in human tissues in vivo. The aim of our study was to investigate the response of ruptured Achilles tendon treated with PRP. METHODS Tendon tissue biopsy samples were obtained from 20 patients with ruptured Achilles tendon by means of ultrasound-guided needle biopsies from the healing area of the Achilles tendon 6 weeks after treatment with PRP or placebo controls (10 patients each). All samples were embedded in paraffin wax, sectioned, and stained with haematoxylin and eosin and alcian blue. Immunohistochemistry markers were used to identify collagen I and III, lymphocytes (CD45), proliferation (KI67), and blood vessels (CD34). All images were masked and analysed with Image J software. FINDINGS Cellularity and glycosaminoglycans content were significantly higher in PRP-treated tendons than in controls (p=0·01 and p<0·001, respectively). Fibre structure of the tissue was significantly better in the PRP group than in the control tissue (p<0·001). Although both groups showed high collagen I staining, content of collagen I was significantly higher in PRP-treated tendons than in control tendons (p=0·0079), whereas collagen III content was not different (p=1·0). The ratio of collagen III to collagen I was significantly lower in PRP samples (p=0·007). There was no significant difference in CD45 expression (p=0·33). However, PRP samples had fewer blood vessels than did control samples (p=0·023). The overall modified Bonar score was significantly lower in PRP samples, which indicates improved early tendon healing. INTERPRETATION This is the first study, to our knowledge, to report the immunohistochemical response of ruptured human Achilles tendon to PRP. The findings reveal that locally applied PRP enhanced the maturity of the healing tendon tissues by promoting better collagen I deposition, decreased cellularity, less vascularity, and higher glycosaminoglycan content when compared with control samples. Further work is required to determine the longer term effects of the use of PRP in musculoskeletal diseases. FUNDING National Institute for Health Research.

Isolated anterolateral fracture of the coronoid process of the ulna: a case report

The coronoid process of the proximal ulna articulates with the trochlea of the humerus and, as such, is important in preventing posterior displacement of the ulna relative to the humerus, whilst also acting as a key stabilizer against varus stress in an extended elbow. Three types of coronoid fracture were originally described by Regan and Morrey. All were transverse fractures across the coronal plane of the coronoid process, with type I described as an avulsion of the tip of the process, type II a fracture involving up to 50% of the process, and type III a fracture involving more than 50% of the process. A concurrent elbow dislocation or associated fracture was associated with 14%, 56%, and 80% of type I, II, and III cases, respectively. The injury has been reported to occur in rotational flexion, axial loading in extension, and hyperextension of the elbow joint. The Regan and Morrey classification of ulna coronoid process fractures was subsequently modified by O’Driscoll into type 1 (transverse fracture of the tip of the coronoid process), type 2 (fracture of the anteromedial facet of the coronoid process), and type 3 (fracture of the base of the coronoid process) fractures. This case report discusses an isolated anterolateral fracture of the coronoid process of the ulna without ligament disruption, which we believe is the only available report of such an injury.

Platelet-Rich Plasma in Regenerative Medicine

The clinical application of platelet-rich plasma (PRP) has been increasing sharply in the last two decades. Its role as a potential regenerative agent and ease of application have allowed it to take huge share in the fast-evolving biological therapy field. The reported effect of PRP on a range of tissue types including bone, cartilage, tendon and muscle has attracted clinical interest in fields such as trauma, orthopaedic, maxillofacial and plastic surgery where effective healing of tissues is critical for successful outcome. The results of in vitro and animal studies that largely report positive effects of PRP on cellular and matrix regeneration have been the main drive for its translation to clinical settings. Despite the lack of appropriately powered trials, PRP administration remains an attractive strategy given its cost-effective, minimally invasive nature and the autologous nature of PRP. In this chapter, the current literature on the use of PRP in regenerative medicine is reviewed highlighting both some of the controversy surrounding this approach and some emerging clinical applications. A new PRP classification system is presented to allow better description of the variable clinical PRP products and their correlated outcome.

Controlled motion strain measurement using lateral speckle tracking in Achilles tendons during healing

Ultrasound elastography imaging is being increasingly used to indicate the functional properties of musculoskeletal pathologies. Usually, this involves a real-time free-hand acquisition which has questionable consistency and does not provide a material deformation that is representative of the material function. This paper presents a novel method for acquiring quantitative ultrasound lateral strain images of in-vivo Achilles tendons in a controlled manner using a computer controlled foot articulation device and a novel 2D multiscale, multi-compression, sub-pixel precision block matching algorithm. The method has been applied to a longitudinal study of 21 patients with Achilles tendon rupture which have repeated data points taken over 24 weeks of therapy. The controlled lateral motion results are compared to the more conventional freehand axial-decompression method, and also against clinical measures. The results show that the controlled lateral motion strain images have a smaller standard deviation of average value than the freehand decompression motion (σlat = 0.77%, σcomp =1.74%) and a tighter fitting to a strain improvement model which followed the same form as clinical measures of patient healing over the group (Rlat2 = 0.78, Rcomp2 = 0.34).

Platelet rich Plasma in Achilles Tendon Healing 2 (PATH-2) trial: protocol for a multicentre, participant and assessor-blinded, parallel-group randomised clinical trial comparing platelet-rich plasma (PRP) injection versus placebo injection for Achilles tendon rupture.

Background Achilles tendon injuries give rise to substantial long-lasting morbidity and pose considerable challenges for clinicians and patients during the lengthy healing period. Current treatment strategies struggle to curb the burden of this injury on health systems and society due to lengthy rehabilitation, work absence and reinjury risk. Platelet-rich plasma (PRP) is an autologous preparation that has been shown to improve the mechanobiological properties of tendons in laboratory and animal studies. The use of PRP in musculoskeletal injuries is on the increase despite the lack of adequately powered clinical studies. Methods and design This is a multicentre randomised controlled trial to evaluate the efficacy and mechanism of PRP in patients with acute Achilles tendon rupture (ATR). All adults with acute ATR presenting within 12 days of the injury who are to be treated non-operatively are eligible. A total of 230 consenting patients will be randomly allocated via a remote web-based service to receive PRP injection or placebo injection to the site of the injury. All participants will be blinded to the intervention and will receive standardised rehabilitation to reduce efficacy interference. Participants will be followed up with blinded assessments of muscle–tendon function, quality of life, pain and overall patient’s functional goals at 4, 7, 13, 24 weeks and 24 months post-treatment. The primary outcome is the heel-rise endurance test (HRET), which will be supervised by a blinded assessor at 24 weeks. A subgroup of 16 participants in one centre will have needle biopsy under ultrasound guidance at 6 weeks. Blood and PRP will be analysed for cell count, platelet activation and growth factor concentrations. Ethics and dissemination The protocol has been approved by the Oxfordshire Research Ethics Committee (Oxfordshire Research Ethics Committee A, reference no 14/SC/1333). The trial will be reported in accordance with the CONSORT statement and published in peer-reviewed scientific journals. Trial registration number ISRCTN: 54992179, assigned 12 January 2015. ClinicalTrials.gov: NCT02302664, received 18 November 2014. UK Clinical Research Network Study Portfolio Database: ID 17850.

Quantitative biomechanical comparison of ankle fracture casting methods

Abstract The incidence of ankle fractures is increasing rapidly due to the ageing demographic. In older patients with compromised distal circulation, conservative treatment of fractures may be indicated. High rates of malunion and complications due to skin fragility motivate the design of novel casting systems, but biomechanical stability requirements are poorly defined. This article presents the first quantitative study of ankle cast stability and hypothesises that a newly proposed close contact cast (CCC) system provides similar biomechanical stability to standard casts (SC). Two adult mannequin legs transected at the malleoli, one incorporating an inflatable model of tissue swelling, were stabilised with casts applied by an experienced surgeon. They were cyclically loaded in torsion, measuring applied rotation angle and resulting torque. CCC stiffness was equal to or greater than that of SC in two measures of ankle cast resistance to torsion. The effect of swelling reduction at the ankle site was significantly greater on CCC than on SC. The data support the hypothesis that CCC provides similar biomechanical stability to SC and therefore also the clinical use of CCC. They suggest that more frequent re-application of CCC is likely required to maintain stability following resolution of swelling at the injury site.