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  • The Use of Platelet-Rich and Platelet-Poor Plasma to Enhance Differentiation of Skeletal Myoblasts

    Abstract

    Objectives: Platelet-rich plasma (PRP) has been has been used to augment tissue repair and regeneration after musculoskeletal injury. However, there is increasing clinical evidence that PRP, and related blood products, do not show a consistent clinical effect. The purpose of this study is to compare the effects of non-neutrophil containing PRP (LP-PRP), modified LP-PRP (Mod LP-PRP) where TGF-β1 and myostatin (MSTN) were depleted, and platelet poor plasma (PPP) on human skeletal muscle myoblast (HSMM) differentiation. Our hypothesis was that LP-PRP would lead to myoblast proliferation, not differentiation, while modifications of PRP preparations will increase myoblast differentiation, which is necessary for skeletal muscle regeneration.

    Methods: Blood was simultaneously processed from eight healthy human donors to create LP-PRP, Mod-LP-PRP, PPP and second spin (ss) PRP and Mod-PRP groups. Mod-PRP was created using antibodies attached to sterile beads to remove TGF- β1 and MSTN. The biologics were then individually added to human skeletal muscle myoblasts (HSMM) and were analyzed over four days. Analysis for induction into myoblast proliferation and differentiation pathways included Western blot and RT-PCR, as well as confocal microscopy to assess for polynucleated myotubule formation.

    Results:LP-PRP treatment lead to increased myoblast proliferation compared to PPP (1.01 x 106 vs 5.1 x 105 cells), but showed no evidence differentiation into muscle cells either by myotubule formation or via inducing myosin heavy chain (MHC) RNA compared to negative controls (0.1x fold change; p>0.05). TGF- β1 and MSTN were successfully depleted in Mod-PRP, but this modification did little to improve myoblast differentiation (0.2x fold change MHC RNA vs control; p>0.05). Application of PPP to cultures induced myoblast differentiation that included visible multinucleated myotubule formation and MHC induction compared to negative controls (9.8x fold change; p<0.05). A second centrifugal spin (removes platelets) lead to a significant increase in myoblast differentiation in PRP and Mod-PRP preparations, similar to the level of PPP and the 2% horse serum positive control (8.0x vs 6.7x vs 9.8x vs 6.0x fold increase in MHC RNA, respectively; all p<0.05 compared to LP-PRP, Mod-LP-PRP and negative controls). Western blot and RT-PCR analyses confirmed that MSTN and TGF-β1 were further depleted in all groups, including Mod-LP-PRP, that were subjected to a second spin.

    Conclusion: PPP, and PRP preparations subjected to a second spin to remove platelets, lead to induction of myoblast cells into the muscle differentiation pathway, while unmodified PRP lead to induction into the proliferation pathway. These results indicate that traditionally formulated PRP should not be used to induce muscle regeneration. Laboratory evidence suggests that platelet poor plasma (PPP) or LP-PRP subjected to a second spin to remove platelets should be used to stimulate myoblast differentiation, which is necessary for skeletal muscle regeneration. Clinical studies will be required to confirm the effect of these biologics on muscle regeneration.

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  • Proliferative injection therapy for osteoarthritis: a systematic review

    Abstract

    Purpose: To systematically analyse randomised controlled trials (RCTs) about efficacy and safety of proliferative injection therapy (prolotherapy) for treatment of osteoarthritis (OA).

    Methods: CENTRAL, Embase and MEDLINE were searched. Two reviewers independently conducted screening and data extraction. RCTs were assessed with the Cochrane risk of bias tool. Type of treatment, study design, dosing, efficacy outcomes and safety outcomes were analysed. The protocol was registered in PROSPERO (CRD42016035258).

    Results: Seven RCTs were included, with 393 participants aged 40-75 years and mean OA pain duration from three months to eight years. Follow-up was 12 weeks to 12 months. Studies analysed OA of the knee joint (n = 5), first carpometacarpal joint (n = 1) and finger joints (n = 1). Various types of prolotherapy were used; dextrose was the most commonly used irritant agent. All studies concluded that prolotherapy was effective treatment for OA. No serious adverse events were reported. The studies had considerable methodological limitations.

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  • Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair

    Abstract

    Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI), focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery.

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  • Stem Cells in Bone and Articular Cartilage Tissue Regeneration

    Abstract

    Multiple factors including trauma, infection, ageing, obesity and tumours result in bone and cartilage defects. The regeneration and functional restoration of bone and cartilage remains a significant clinical challenge. \'Autologous grafts\' continue to remain the \'gold standard\' in both bone and cartilage regeneration but stem cell-based therapies offer great promise in both these areas. Despite the plethora of stem cells that exist within the human body, the challenge remains in identifying the most beneficial cell type, assessing their availability, expansion under cGMP culture conditions, differentiation potential and functional restoration capacity. Embryonic stem cells; mesenchymal stem cells from the bone marrow, synovial fluid, adipose tissue and umbilical cord; and primary articular chondrocytes are some of the candidate cell types that are extensively studied in the context of bone (and cartilage) regeneration. The limited regeneration potential of cartilage adds further complexity to cartilage tissue engineering compared to the bone. However, major bone reconstruction as in the case of large bone defects due to tumour resection, fractures, and skeletal deformities is equally challenging. Incorporation of novel biomaterials, understanding the optimal cell-scaffold interactions, the addition of growth factors and provision of molecular cues are all essential in achieving effective tissue regeneration. Intensive effects in tissue regeneration can actually predispose to tissue hypertrophy, which also limits functional capacity. The current state of-the-art in both bone and cartilage regeneration is reviewed in this chapter, which highlights the importance of combined approaches involving stem/progenitor cells, biomolecules and/or biomaterials for therapies as well as rehabilitation and improvement in quality of life.

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  • Comparative performance of the protocol of plasma rich in growth factors - universal 1 (PRGF-U1) for obtaining platelet rich plasma

    Abstract

    Objective: To compare the platelet concentration obtained after application of the protocol of plasma rich in growth factors - universal 1 (PRGF-U1) and the protocol of Anitua and Andia (PRP-A) for obtaining platelet rich plasma.

    Material and Method: A descriptive, cross-sectional and comparative study was carried out with a simple random probabilistic sample consisting of 16 patients who attended the Periodontics service of the Unit of Second Specialization in Stomatology of the National University of Trujillo. Five blood samples were obtained from each patient, after applying a health questionnaire to rule out any disease or drug consumption, in order to obtain the baseline platelet concentration and that obtained after PRGF-U1 and PRP-A. To compare the platelet concentrations of the two protocols, Student\'s t-test was used considering a significance level of p <0.05.

    Results: The baseline platelet concentration was 371,250 ± 68,203 platelets/μL, for PRGF-U1 it was 747,875 ± 121,645 platelets/μL and for PRP-A it was 595,000 ± 129,202 platelets/μL. A statistically significant difference (p<0.001) was found between both protocols.

    Conclusion: The PRGF-U1 protocol yielded a higher platelet concentration compared to the Anitúa and Andía protocol.

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  • Platelet-rich plasma (PRP) for knee disorders

    Abstract

    • Platelet-rich plasma (PRP) is an autologous blood product with platelet concentrations above baseline values. The process involves the extraction of blood from the patient which is then centrifuged to obtain a concentrated suspension of platelets by plasmapheresis. It then undergoes a two-stage centrifugation process to separate the solid and liquid components of the anticoagulated blood. PRP owes its therapeutic use to the growth factors released by the platelets which are claimed to possess multiple regenerative properties.
    • In the knee, PRP has been used in patients with articular cartilage pathology, ligamentous and meniscal injuries.
    • There is a growing body of evidence to support its use in selected indications and this review looks at the most recent evidence. We also look at the current UK National Institute of Health & Clinical Excellence (NICE) guidelines with respect to osteoarthritis and the use of PRP in the knee.

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  • Effect of ozone and methylprednisolone treatment following crush type sciatic nerve injury.

    Abstract

    Purpose: To assess and compare the histopathological effects of ozone therapy and/or methylprednisolone (MPS) treatment on regeneration after crush type sciatic nerve injury.

    Methods: Forty Sprague-Dawley male rats were randomly allocated into four groups. Four groups received the following regimens intraperitoneally every day for 14 days after formation of crush type injury on sciatic nerve: Group I: ozone (20mcg/ml); Group II: methylprednisolone (2mg/kg); Group III: ozone (20 mcg/ml) and methylprednisolone (2mg/kg); Group IV: isotonic saline (0.9%). The histomorphological evaluation was made after biopsies were obtained from the sites of injury.

    Results: Significant differences were noted between groups in terms of degeneration (p=0.019), nerve sheath cell atrophy (p=0.012), intraneural inflammatory cellular infiltration (p=0.002), perineural granulation tissue formation (p=0.019), perineural vascular proliferation (p=0.004), perineural inflammatory cellular infiltration (p<0.001) and inflammation in peripheral tissue (p=0.006). Degeneration was remarkably low in Group III, while no change in nerve sheath cell was noted in Group II.

    Conclusion: The combined use of methylprednisolone and ozone treatment can have beneficial effects for regeneration after crush type nerve injury.

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  • Technical Innovation Case Report: Ultrasound-Guided Prolotherapy Injection for Insertional Achilles Calcific Tendinosis

    Abstract

    We describe the use of ultrasound guidance for hyperosmolar dextrose (prolotherapy) injection of the distal calcaneal tendon specifically just anterior to identified enthesophytes in patients with insertional Achilles calcific tendinosis refractory to conservative treatment. This specific technique has not to our knowledge been described or used in literature previously.

    Introduction: Insertional Achilles tendinosis is a common chronic overuse injury in both athletes and nonathletes alike. Symptoms can last anywhere from weeks to years and cause significant difficulties in daily activities. Treatments can range widely from rest, NSAIDs, topical medications, physical therapy, various injections, and in extreme cases surgical intervention.

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  • The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials

    Abstract

    Background: Quite a few randomized controlled trials (RCTs) investigating the efficacy of platelet-rich plasma (PRP) for treatment of knee osteoarthritis (OA) have been recently published. Therefore, an updated systematic review was performed to evaluate the temporal effect of PRP on knee pain and physical function.

    Methods: Pubmed, Embase, Cochrane library, and Scopus were searched for human RCTs comparing the efficacy and/or safety of PRP infiltration with other intra-articular injections. A descriptive summary and quality assessment were performed for all the studies finally included for analysis. For studies reporting outcomes concerning Western Ontario and McMaster Universities Arthritis Index (WOMAC) or adverse events, a random-effects model was used for data synthesis.

    Results: Fourteen RCTs comprising 1423 participants were included. The control included saline placebo, HA, ozone, and corticosteroids. The follow-up ranged from 12 weeks to 12 months. Risk of bias assessment showed that 4 studies were considered as moderate risk of bias and 10 as high risk of bias. Compared with control, PRP injections significantly reduced WOMAC pain subscores at 3, 6, and 12 months follow-up (p = 0.02, 0.004, <0.001, respectively); PRP significantly improved WOMAC physical function subscores at 3, 6, and 12 months (p = 0.002, 0.01, <0.001, respectively); PRP also significantly improved total WOMAC scores at 3, 6 and 12 months (all p < 0.001); nonetheless, PRP did not significantly increased the risk of post-injection adverse events (RR, 1.40 [95% CI, 0.80 to 2.45], I 2 = 59%, p = 0.24).

    Conclusions: Intra-articular PRP injections probably are more efficacious in the treatment of knee OA in terms of pain relief and self-reported function improvement at 3, 6 and 12 months follow-up, compared with other injections, including saline placebo, HA, ozone, and corticosteroids.

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  • A Randomized Controlled Study to Evaluate the Effectiveness of Local Platelet Rich Plasma (PRP) Injection for the Management of the Cases of Planter Fasciitis - Final Outcome of 179 Cases at 12 Months

    Abstract

    Introduction: Plantar fasciitis is an inflammation of the plantar fascia at the bottom of the foot. Though pathology of plantar fasciitis remains ill understood, there is evidence to suggest that it is probably initiated by repeated micro trauma. Numerous methods have been advocated for treating plantar fasciitis, including rest, NSAID\'s, night splints, foot orthosis, stretching protocols and ESWT (extra corporeal shock wave therapy) ,local laser application, autologous blood injection and local ultrasound application. Platelet rich plasma (PRP) is promoted as an ideal autologous biological blood-derived product, which can be exogenously applied to various tissues where it releases high concentrations of platelet derived growth factors that enhance wound healing, bone healing and also tendon healing. In current study evaluate the effectiveness of local infiltration of autologous platelet rich plasma (PRP) and compared the results with control group.

    Method: Present study conducted in department of orthopedics of a tertiary level 1000 bedded Super specialty Medical Collage situated in rural area of North India. Cases were selected from the patients attending routine OPD from January 2007 to December 2015 at orthopedics department. 10 ml of a patient\'s own blood was collected via blood draw, maintaining sterile technique, with SYRINGE and then mixed with 2 ml Acid citrate dextrose (anticoagulant). This was then put in Autologous Platelet Separator System (1500 RPM for 5 minutes), yielding platelet rich plasma (PRP) as supernatant. Under sterile conditions, patients were receiving a 3 cc PRP injection (consisting of their own PRP) into the origin of the plantar fascia and site of maximum tenderness. We followed up patients at 2 weeks, 4 weeks, 8 weeks, 12 weeks and final at 52 weeks. The results tabulated as per the Performa. We used visual analogue scale (VAS) for assessment of pain relief in two groups.

    Results: At the start of study the mean VAS of control group was 6.5 and mean VAS of case group (PRP) was 6.6. The mean VAS score in case group (PRP) decreases from baseline 6.6 at start to 0.54 at 52 wk during follow up. We noticed that there was maximum decrease in mean VAS score in case group from first week (VAS-6.6) to 12 weeks (VAS-1.7). We concluded that PRP injection at planter fasciitis site have much better outcome in relation to visual analogue score(VAS) and result difference was statistically significant.

    Conclusion: Planter fasciitis is a very disabling disorder of foot leaving to very discomforting life and day to activity. Autologous platelet rich plasma (PRP) infiltration at the most tender part of heel is a effective method of management of these cases as compared to conservative management. This method also shown negligible complication rate and low recurrence rate. Conservative management of these cases had shown poor long term results.

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  • Generation of stem cell-based bioartificial anterior cruciate ligament (ACL) grafts for effective ACL rupture repair

    Abstract

    Introduction: Regenerative medicine (RM) is an interdisciplinary field of research and clinical applications focus on the repair, replacement, or regeneration of cells, tissues and organs to restore impaired function. RM employs technological breakthroughs such as those used in tissue engineering (TE) (i.e. biodegradable, biomimetic biopolymers, nanotechnology, biosensors etc) in combination with the powerful differentiation capacity of stemcells. Indeed, adipose tissue (AT) is a rich source ofmultipotential stromal cells (MSCs) that can be successfully differentiated towards mesoderm-related lineages such as osteoblasts, adipocytes, chondroblasts and fibroblasts representing a good overall option for autologous regenerative applications. Adult tissues, however, contain only committed stem cells that are multi- or even oligopotent. The use of human embryonic stem cells (hESCs) for medical applications is prohibited for legal/ethical (commercialization of life) andmedical (immune rejection of heterologous tissue) reasons. Thus, generation of induced pluripotent stem cells (iPSCs) by reprogramming of terminally differentiated cells (Takahashi and Yamanaka, 2006) offers the possibility for autologous regeneration of any tissue using pluripotent stem cells.

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  • Clinical effectiveness in severe knee osteoarthritis after intra-articular platelet-rich plasma therapy in association with hyaluronic acid injection: three case reports

    Abstract

    Osteoarthritis (OA) is a degenerative disorder resulting from loss of joint cartilage and underlying bone and causes pain and loss of function. The treatment ofk:nee OA is still a challenge because of the poor self-regeneration capacity of artilage. The nonslligical interventions include control of the aggravating factor (such as weight control and the use of walking aids), symptomatic treatment (such as acetaminophen or nonsteroidal anti-inflammatory drugs), prolotherapy, and viscosupplementation. However, the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) has not been widely used because of lack of clinical evidence and several limitations in patients with severe knee OA. Three patients who suffered from knee pain and poor walking endurance were diagnosed with advanced knee OA They underwentPRP treatment in association with intra-articular HA injection and showed pain relief and functional improvement. The follow-up standard weight-bearing X-ray images of knees also confirmed the improvement and indicated the possibility of regeneration of the articular cartilage. These cases provide clinical and radiographic evidence for a new therapy for advanced knee OA This treatment strategy of PRP in association with HA injection can offer a chance to treat severe knee OA, rather than immediate surgery, or a chance for those who cannot undergo surgery. It can also postpone the need of arthroplasty and can significantly improve the daily activity function.

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  • Comparison of different methods of centrifugation for preparation of platelet - rich plasma (PRP)

    Abstract

    Introduction: Platelet-rich plasma(PRP) has wide clinical applications which have been proved by various studies. There are various methods available now a days to prepare PRP but no standard protocol determining the time and centrifugation speed is available. This variation in the reported methods may produce samples with different platelet concentrations which may induce different clinical responses. Hence, the aim of the present study was to compare the different methods of centrifugation for preparation of platelet - rich plasma by estimating the platelet concentration in them.

    Methods: Whole blood was drawn from 50 healthy volunteers into two citrate tubes which were subjected to different centrifugation speed and time. The first tube underwent double spin at 100g (soft spin) and 400g (hard spin) respectively, for 10 minutes; whereas the second tube underwent single spin at 100g for 10 minutes. The platelet counts before and after centrifugations were then compared.

    Results: Single spin method yielded a plate let concentration factor of 2.19 as compared with the double spin method where, actually the platelet counts reduced (platelet concentration factor=0.83).

    Conclusion: From the above findings we conclude that single centrifugation method is better than double centrifugation method in preparation of platelet rich plasma as evidenced by the high platelet concentration factor (2.19).

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  • Efficacy of platelet-rich plasma for clinical outcomes after total knee arthroplasty: a systematic review and meta-analysis

    Abstract

    Objective: The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) and non-RCTs were to evaluate the effect of platelet-rich plasma (PRP) versus placebo on the patients receiving total knee arthroplasty (TKA).

    Methods: In April 2016, a systematic computer-based search was conducted in the Pubmed, ISI Web of Knowledge, Embase, Cochrane Database of Systematic Reviews and Chinese Wanfang data - base. This systematic review and meta-analysis were performed according to the PRISMA statement criteria. The primary endpoint was the range of motion (ROM), which represents the function after TKA. The Western Ontario Mc - Master Universities Osteoarthritis Index Bellamy (WOMAC), pain at 24 h, 48 h and 7 day and hemoglobin (Hb) at 24h after TKA were also to assess the effect of PRP on the function and pain after TKA. The complications of infection were also compiled to assess the safety of PRP. After testing for publication bias and heterogeneity across studies, data were aggregated for random-effects modeling when necessary.

    Results:Ten clinical trials with 1001 patients were included in the meta-analysis. The pooled results indicated that administration of PRP significantly increase ROM at third day (mean difference (MD) = 4.05, 95% CI = 1.58-6.52; P = 0.001) and 3 month postoperatively (MD = 3.12, 95% CI = 0.94-5.29; P = 0.005). There is no statistically difference between the two groups in terms of WOMAC questionnaire score at 3 month, pain intensity at 24 h, 48 h and 7 day and Hb at 24 h after TKA. There is no statistically significant difference between the PRP versus placebo in terms of the occurrence of infection (relative risk (RR) = 0.64, 95% CI = 0.19-2.14, P = 0.464).

    Conclusion: Based on the current meta-analysis, PRP can limitedly increase the ROM after TKA in short and long period. What\'s more, PRP has no effects on the WOMAC score, pain scores and the occurrence of infection. More RCTs and high quality studies are still needed to identify the efficacy and safety of PRP after TKA.

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  • Usefulness of strain elastography of the musculoskeletal system

    Abstract

    Ultrasound elastography is a widely used technique for assessing the mechanical characteristics of tissues. Although there are several ultrasound elastography techniques, strain elastography (SE) is currently the most widely used technique for visualizing an elastographic map in real time. Among its various indications, SE is especially useful in evaluating the musculoskeletal system. In this article, we review the SE techniques for clinical practice and describe the images produced by these techniques in the context of the musculoskeletal system. SE provides information about tissue stiffness and allows real-time visualization of the image; however, SE cannot completely replace gray-scale, color, or power Doppler ultrasonography. SE can increase diagnostic accuracy and may be useful for the follow-up of benign lesions.

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  • Analgesic Effect of Caudal 5% Dextrose in Water in Chronic Low Back Pain. A Randomized Controlled Trial of Epidural Injection

    Abstract

    Background: Hypertonic dextrose injection (prolotherapy) is reported to reduce pain including non-surgical chronic low back pain (CLBP), and subcutaneous injection of 5% dextrose is reported to reduce neurogenic pain hyperalgesia and allodynia. The mechanism in both cases is unclear, though a direct effect of dextrose on neurogenic pain is proposed. This study assessed the short-term analgesic effects of epidural 5% dextrose compared with saline for non-surgical CLBP.

    Methods: Randomized double-blind (injector, participant) controlled trial. Adults with moderate-to-severe non-surgical low back pain with radiation to gluteal or leg areas for at least 6 months received a single epidurogram-confirmed epidural injection of 10 mL of 5% dextrose or 0.9% saline using a published vertical caudal injection technique. The primary outcome was change in a numerical rating scale (NRS, 0 - 10 points) pain score between baseline and 15 minutes; and 2, 4, and 48 hours and 2 weeks post-injection. The secondary outcome was percentage achieving 50% or more pain improvement at 4 hours.

    Results and Conclusions: No baseline differences existed between groups; 35 participants (54 ± 10.7 years old; 11 female) with moderate-to-severe CLBP (6.7 ± 1.3 points) for 10.6 ± 10.5 years. Dextrose participants reported greater NRS pain score change at 15 minutes (4.4 ± 1.7 vs 2.4 ± 2.8 points; P = 0.015), 2 hours (4.6 ± 1.9 vs1.8 ± 2.8 points; P = 0.001), 4 hours (4.6 ± 2.0 vs 1.4 ± 2.3 points; P = 0.0001), and 48 hours (3.0 ± 2.3 vs 1.0 ± 2.1 points; P = 0.012), but not at 2 weeks (2.1 ± 2.9 vs 1.2 ± 2.4 points; P = 0.217). Eighty four percent (16/19) of dextrose recipients and 19% (3/16) of saline recipients reported ≥ 50% pain reduction at 4 hours (P < 0.001). These findings suggest a neurogenic effect of 5% dextrose on pain at the dorsal root level; waning pain control at 2 weeks suggests the need to assess the effect of serial dextrose epidural injections in a long-term study with robust outcome assessment.

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  • Distribution of Platelet-rich Plasma after Ultrasound-Guided Injection for Chronic Elbow Tendinopathies

    Abstract

    Characteristics of the spreads of platelet-rich plasma (PRP) are not widely known despite commonly use. This study aims to evaluate whether PRP stays within the injected area by using ultrasonography, to improve understanding of the spreads of intratendinous injected PRP. Thirty-nine patients (15 males, 24 females; mean age, 49.3 years), who had symptoms on their elbows (> 6 months) and diagnosed as lateral (25 elbows) or medial (14 elbows) tendinopathies of elbow, were included. The severity of tendon pathology was assessed by ultrasonography as tear or no tear. Immediately after ultrasound-guided PRP injection, ultrasound images were evaluated to assess the area of PRP distribution, which was defined as the presence of fluid or microbubbles. Ultrasound revealed that 13 elbows had tendon tear and 26 had no tear, respectively. Post-injection ultrasound confirmed the injected PRP was within the tendon in all cases. The mean distance of distribution from the injection site was 12.6 mm (5.0-26.0 mm). There was no difference in the distance of PRP distribution between tendon tear and no tear. Injected PRP spread to soft tissue outside the tendon in 20 of 39 cases. Intra-articular extension of PRP was observed in 5 cases. Although PRP remained intratendinous after the injection in all cases, some portion tended to spread outside from the injection site in a short space of time. Postinjection ultrasonographic imaging has a value for observing the spreading patterns of intratendinous PRP injection.

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  • Platelt-Rich Plasma Enhances Cartilage Integration: A BioEngineered In Vitro Model

    Abstract

    Osteoarthritis (OA) is a debilitating disease characterised by degradation of articular cartilage and subchondral bone remodeling. Current therapies for early or midstage disease do not regenerate articular cartilage, or fail to integrate the repair tissue with host tissue, and therefore there is great interest in developing biological approaches to cartilage repair. We have shown previously that platelet-rich plasma (PRP) can enhance cartilage tissue formation. PRP is obtained from a patient\'s own blood, and is an autologous source of many growth factors and other molecules which may aid in healing. This raised the question as to whether PRP could enhance cartilage integration. We hypothesise that PRP will enhance integration of bioengineered cartilage with native cartilage.

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  • Prolotherapy for Lumbar Segmental Instability Associated with Degenerative Disc Disease

    Abstract

    Prolotherapy is an injection-based therapy that may be used in the management of chronic low back pain. In principle, injection solutions are formulated to produce an inflammatory response, which in turn promotes ligamentous and tendinous regeneration.

    This case study series offers some ideas as to how Prolotherapy might be advantageous in the management of discogenic low back pain through improving vertebral segmental stability.

    When the disc is of normal height, the ligaments that hold the spine together remain at normal length. As the disc height decreases as in degenerative disc disease, the vertebrae move closer together. The resultant loss of spinal ligament tension may allow vertebral segmental instability, leading to chronic pain.

    Materials & Methods: The study analysed twenty-one male & female patients aged 35 to 73 years with chronic low back pain and MRI-confirmed low lumbar DDD (some with multi-level disease). They underwent 3 sets of fluoroscopically-guided Prolotherapy injections 1-3 weeks apart. Oswestry scores were analysed pre-Prolotherapy, at 3 months and at 1 year. All Oswestry scores were recorded on 14 patients, with the remainder only having pre and 1 year follow-up scores reported.

    Results: Pre-Prolotherapy Oswestry scores ranged in all patients from 12 to 44. 12 patients reported ADL or functional improvement scores of 80% or greater. 3 patients reported ADL or functional improvement scores of 70% at 1 year follow up. 3 patients also reported complete resolution of LBP and 100% ADL improvement at one-year follow-up with one of these patients becoming symptom-free at 3 months with results maintained at one-year follow-up. On patients for whom 3-month follow-up data was available, there was typically further improvement on ADLs and pain reduction on one-year follow-up. 3 patients reported no ADL or pain reduction benefit at all from the Prolotherapy with one of these patients actually reporting worse LBP and ADL scores at both 3 month and one-year post Prolotherapy. An inverse pattern of reduced pain scores in relation to improved ADL function was noted.

    Conclusions: These findings are consistent with the conclusions of other studies, in that Prolotherapy, in conjunction with rehabilitation would appear to be an effective part of the management pathway for discogenic low back pain associated with degenerative disc disease of the lumbar spine.

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  • Injection Therapy: Intra-articular Platelet-Rich Plasma and Stem Cell Therapy

    Abstract

    Platelet-rich plasma (PRP) has been touted in the sports medicine and orthopaedic surgery communities as a remedy with the ability to bridge the gap between conservative, pain relieving therapies and surgical interventions. Its theoretical advantages include its ability to enhance wound healing, decrease pain and improve function.

    There has also been much excitement about the multipotential nature of mesenchymal stem cells (MSCs), with the potential to regenerate different types of musculoskeletal tissue from cartilage to meniscus.

    Problems with both therapies abound. As yet, there is no common consensus as to what constitutes PRP, its preparation, or the method of its activation. Similarly, MSCs can have multiple origins, be induced in different methods and delivered in a variety of forms. Thus, at present, the evidence to substantiate the claims of either therapy is sparse or fails to be robust enough to support the arguments for its use.

    Our chapter provides an evidence-based insight into the background, preparation and clinical use of both PRP and MSCs, two therapies which have much to offer in regenerating and preserving tissue within the adult knee.

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