Diversos tipos de produtos ortobiologicos

Plasma rico em plaquetas

O plasma rico em plaquetas (PRP) é amplamente definido como plasma com uma concentração de plaquetas mais elevada do que o sangue total.

O termo PRP foi cunhado por hematologistas na década de 1970 e foi inicialmente usado como um produto de transfusão para tratar pacientes com trombocitopenia. Passaram-se quase 30 anos antes de seu uso na medicina musculoesquelética. O plasma rico em plaquetas pode ser posteriormente categorizado com base na sua composição celular, mais comumente como PRP rico em leucócitos ou PRP pobre em leucócitos. As plaquetas participam da formação do coágulo sanguíneo e da modulação da inflamação e cura, que são alcançadas por meio da liberação de vários fatores de crescimento, citocinas e quimiocinas das mitocôndrias das plaquetas e de todos os 3 grânulos (denso, alfa e lisossomal). Geralmente, acredita-se que 70% a 95% dos fatores de crescimento das plaquetas são liberados dentro de 10 minutos da ativação plaquetária, que ocorre após a exposição ao colágeno do tecido conjuntivo ou a adição de um ativador plaquetário, como cloreto de cálcio ou trombina, com o restante sendo liberado lentamente ao longo de alguns dias. 77,80,81 Embora a evidência da eficácia clínica do PRP em uma variedade de condições musculoesqueléticas esteja evoluindo, o PRP é usado principalmente para tratar tendinopatias e osteoartrite (OA). 

Plasma rico em plaquetas para tendinopatia

Um resumo das meta-análises recentes e revisões sistemáticas que avaliam a eficácia e os principais eventos adversos das injeções de PRP para tendinopatia é apresentado em vários estudos.
Para tendinopatia , os dados mais robustos que dão suporte ao tratamento com injeções de PRP estão na epicondilopatia lateral. Vários ensaios clínicos randomizados demonstraram que a epicondilopatia lateral responde positivamente às injeções

deTambém houve resultados positivos observados em ensaios clínicos randomizados para o tratamento de tendinopatia do glúteo médio e fasciopatia plantar com PRP. A recente meta-análise de Hurley e cols. sugere que o PRP pode aumentar os reparos do manguito rotador, resultando em melhores taxas de cura, níveis reduzidos de dor e melhores resultados funcionais. Na tendinopatia de Aquiles , ensaios clínicos randomizados e bem delineados não encontraram nenhuma diferença entre as injeções de PRP e solução salina, os resultados na tendinopatia patelar foram mistos.

Plasma rico em plaquetas para osteoartrite

A pesquisa sugere que as injeções de PRP são mais eficazes na redução da dor e na melhora da função do que as injeções de esteróide ou ácido hialurônico para OA do joelho, particularmente em pessoas mais jovens e com doença leve a moderada.

Plasma rico em plaquetas para lesões ligamentares e musculares

A evidência de PRP em lesões ligamentares é limitada. Alguns estudos preliminares sugeriram que o PRP pode facilitar melhores resultados em lesões do ligamento colateral ulnar de espessura parcial do cotovelo, mas um estudo mais amplo e retrospectivo controlado de jogadores da liga principal de beisebol questionou esses achados. 100 Atualmente, a eficácia das injeções de PRP para lesões musculares é desconhecida, pois essa área não foi bem estudada.

Terapias celulares

A terapia celular mais comumente referida envolve células-tronco mesenquimais (CTM). A natureza multipotente dessas células permite que se diferenciem em vários tecidos da linhagem mesenquimal, incluindo osso, cartilagem, tecido adiposo e outros tecidos moles in vitro. No entanto, o mecanismo exato de ação das CTMs in vivo é pouco compreendido. Muitos especialistas acreditam que seu mecanismo de ação primário é por atividade parácrina por causa de sua função secretora, resultando em efeitos antiinflamatórios, imunomoduladores, pró-angiogênicos, antiapoptóticos, antifibróticos e proliferativos. As células-tronco mesenquimais também demonstraram induzir a diferenciação de células residentes e não residentes em tecido funcional, resultando em função melhorada do tecido degenerativo. Embora tenha havido dados in vitro e em animais mostrando preservação e restauração significativa da cartilagem, esses resultados não foram, até agora, demonstrados com qualquer consistência em estudos clínicos usando tratamentos com MSC.

Terapias celulares autólogas para osteoartrite

Atualmente, a literatura que apóia as terapias celulares para condições musculoesqueléticas consiste em algumas ciências básicas e estudos com animais, juntamente com relatos de casos, séries de casos e estudos de coorte em humanos. Os estudos clínicos em humanos se concentraram predominantemente no tratamento da OA do joelho usando aspirado de medula óssea (BMA), concentrado de aspirado de medula óssea (BMAC) e tecido adiposo. Todos os produtos têm uma pequena porcentagem de MSCs, apesar da variação da composição celular. Infelizmente, muitos estudos usaram métodos que estão fora das considerações regulatórias do FDA (por exemplo, expansão da cultura e mais do que manipulação mínima), limitando assim sua aplicabilidade à prática clínica nos Estados Unidos. Uma vez que o produto mais comumente usado é o BMAC, uma pesquisa bibliográfica foi concluída para fornecer um resumo das meta-análises recentes e revisões sistemáticas que avaliam a eficácia e os principais eventos adversos das injeções de BMAC para OA.
O estudo metodologicamente mais sólido até o momento é o ensaio clínico randomizado de Shapiro et al que comparou o BMAC com injeções de solução salina em pacientes com OA de joelho bilateral. Usando um design dentro dos sujeitos, eles relataram reduções semelhantes na dor entre as 2 intervenções em ambos os 6 meses e 12 meses de acompanhamento. Alguns estudos mostraram que as células-tronco derivadas do tecido adiposo podem reduzir o dano e a degeneração da cartilagem articular, reduzindo assim a progressão da OA do joelho. Além disso, estudos bem desenhados são necessários para determinar a eficácia clínica das MSCs para OA.

Terapias celulares autólogas para tendinopatia

Existem poucos estudos avaliando a eficácia das injeções de MSC para o tratamento da tendinopatia , mas existem alguns dados preliminares que sugerem que as MSCs podem diminuir a dor, melhorar a função e induzir uma resposta de cura em lesões de tendão.

A área mais estudada é o manguito rotador. Hernigou e cols. demonstraram que os pacientes que receberam uma injeção de BMAC no momento do reparo do manguito rotador melhoraram a cicatrização, melhoraram a qualidade do reparo e menos retrações do que um grupo de controle que não recebeu uma injeção de BMAC. Além disso, aqueles com um número maior de MSCs em seu BMAC tiveram uma probabilidade maior de sucesso do tratamento do que aqueles com um número menor de MSCs. Embora promissor, é difícil extrapolar esses resultados para outros tendões. No momento, os produtos MSC derivados do tecido adiposo para tendões permanecem na fase pré-clínica de investigação ou estão se encaminhando para os ensaios clínicos. Nenhum estudo bem desenhado, revisões sistemáticas ou meta-análises foram concluídas. Com base nas evidências disponíveis, a eficácia das MSCs na patologia do tendão ainda é desconhecida e mais estudos são necessários.

Produtos Perinatais

Vários produtos perinatais (sangue do cordão umbilical, tecidos amnióticos, Wharton Jelly etc.) estão sendo usados ​​na prática clínica. Os produtos perinatais atualmente disponíveis que foram testados mostraram conter moléculas biologicamente ativas, mas nenhuma célula humana viável, MSC ou outros.

Injecção de PRP para artrite basilar do polegar (articulação CMC)

Os resultados de um estudo em andamento apresentado na Reunião Anual da AAOS indicam que as injeções de plasma rico em plaquetas (PRP) podem ser uma opção de tratamento não cirúrgico eficaz para osteoartrite (OA) da articulação carpometacarpal (CMC)

Nossos resultados mostraram que as injeções de PRP foram associadas ao alívio da dor; função aumentada nas actividades da vida diária; maior liberdade de mobilização, maior força de aperto e aumento da flexão da articulação C-MC, em comparação com a injeção de corticosteroide”, disse a co-autora Marie Badalamente, PhD.

A acção regenerativa dos factores de crescimento, contidos nos grânulos alfa das plaquetas, sobre os condrócitos articulares pode ser um mecanismo potencial para esses efeitos positivos.

“Um Estudo Comparativo de Plasma Rico em Plaquetas (PRP) vs. Injeções de Corticosteróide em Pacientes com Osteoartrite da Articulação Carpometacarpal”

Drª. Marie Badalamente PhD, Professora do Departamento de Ortopedia -- Stony Brook University Hospital

Drª Samantha Muhlrad, Orthopedic Surgeon - Stony Brook University Hospital

Nota: A Dra. Marie Badalemente é professora de Ortopedia na Stony Brook University e membro da National Academy of Inventors . Sua pesquisa se concentra em estudar e desenvolver opções alternativas de tratamento não invasivo. Sua pesquisa sobre a colagenase clostridium histolyticum (CCH) foi o primeiro tratamento com injeção não cirúrgica aprovado pelo FDA para a contratura de Dupuytren, o Xiaflex.

Factores  de crescimento, Citocinas e efeitos biológicos

Os factores de crescimento são moléculas de sinalização solúveis que controlam as respostas celulares por meio da ligação específica de receptores transmembrana nas células-alvo. Regulam células diferenciadas, modulando o crescimento das células e actividade, e por conseguinte, tudo aquilo que é vital para a regeneração dos tecidos e fabrico de tecidos artificiais.

Factores de crescimento aplicados a uma construção de estrutura celular podem ajudar a promover a regeneração do tecido em comparação ao não uso de fatores de crescimento. Os factores de crescimento incluem proteínas morfogenéticas ósseas , factor de crescimento de fibroblastos básico (bFGF ou FGF-2), factor de crescimento epitelial vascular (VEGF) e factor de crescimento transformador-β (TGF-β) ( Ikada, 2006 Lee et al., 2011 ).

Citocinas  são também moléculas de sinalização que se ligam a receptores específicos na superfície de suas células-alvo e induzem vias de sinalização, que então regulam uma série de processos biológicos. Numerosas moléculas diversas são categorizadas em diferentes famílias de citocinas e / ou factores de crescimento. Membros dessas famílias regulam processos como proliferação, activação, diferenciação e migração celular. Além disso, os factores de crescimento controlam os processos necessários para o desenvolvimento, incluindo a organização do tecido, morfogênese e angiogênese. Em organismos adultos, os factores de crescimento também estão envolvidos na regulação do metabolismo, na cicatrização de feridas e na manutenção da homeostase do tecido. A activação constitutiva da sinalização do factor de crescimento está frequentemente associada à transformação celular e tumorigênese.

Lesões musculo-esqueléticas comuns do Corredor

Lesões musculo-esqueléticas comuns do Corredor

(Corrida de Pista, Corrida de Rua, Corrida Cross Country, Corrida de Montanha, Corrida Trail, OCR (obstaculo circuito run) , Corrida de fundo, meia maratona e maratona, corredor esporádico e todas as práticas de Atletismo)

Joelho:

• Sindroma femuro-patelar

• Síndrome da banda iliotibial (IT)

• Tendinite patelar

• Osteoartrose do joelho

• Lesões do menisco

• Lesões musculares e musculo-tendinosas

• Lesões ligamentares

Perna:

• Tendinite de Aquiles

Tornozelo:

• Entorse de tornozelo

• Bursite do calcanhar (retrocalcânea)

Pé:

• Fasceíte plantar

• Metatarsalgia

• Neuroma de Morton

Coluna vertebral:

 • Hernia discal

• Discopatia degenerativa

• Fractura compressiva

Músculos:

• Lesão muscular

• Sindrome compartimental

Osso:

• Fractura de stress

• Canelite

Não surpreende o joelho ser a articulação lesionada com mais frequência em corredores e não corredores, pois os joelhos sofrem pressão igual a aproximadamente 3 vezes o peso do corpo ao caminhar e aproximadamente 5 vezes o peso do corpo ao correr. Em outras palavras, uma pessoa que pesa 68 Kg coloca cerca de 340 Kg de pressão no joelho ao pousar cada passada de corrida.

O joelho durante a corrida é responsável por gerir principalmente a absorção do impacto e dissipar a energia gerada.

Quando os musculos das ancas não conseguem estabilizar e controlar o movimento da corrida é imposto uma sobrecarga nos joelhos que podem gerar lesões degenerativas do menisco principalmente em valgo dinâmico do joelho ( quando a rotula entra em rotação interna)

Síndrome da dor patelofemoral – refere-se à articulação femuro.patelar (femur = osso da coxa e patela = rotula), dolorosa, que se origina entre a rótula e o fêmur. A dor é sentida na frente do joelho, sob ou ao redor da rótula. A origem da dor patelofemoral pode variar e por vezes difícil de identificar. Pode estar subjacente a lesões da cartilagem com conflito articular; pode haver assimetria dos corpos musculares que compôem o quadricipite ou ainda alteração do força dos musculos da anca (gluteos) levando a alteraçoes biomecânicas nos joelhos com aumento de carga na alavanca femuro.patelar. A dor femuro-partelar é geralmente mais perceptível ao subir escadas, caminhar ou correr em subidas.

Síndrome da banda iliotibial (BIT) A síndrome da banda iliotibial é a segunda lesão mais comum do joelho epode afectar corredores tanto novos como experientes resultando de um conflito da banda ilio-tibial com o condilo femural externo. A dor é sentida no lado de fora do joelho ao nivel da rotula e é mais intensa a 30 graus de flexão do joelho O síndrome BIT está mais associada a corridas de longa distância e ao contrário da síndrome da dor femuro-patelar, a dor da BIT costuma piorar a descer escadas ou correr descidas.

Tendinite patelar A tendinite patelar pode causar dor na região anterior do joelho, extremidade inferior da rótula ou extremidade superior da tíbia. A dor pode ser leve e sentida apenas durante o exercício, ou pode ser forte o suficiente para afetar as atividades diárias de uma pessoa, como subir escadas. Tende a ser uma lesão por uso excessivo, comum em corredores, percursos de montanha, de OCR e em actividades de fitness como “power-jump”

Lesões do menisco O menisco é uma cartilagem espessa em forma de C que separa a tíbia e o fêmur, em numero de dois e têm como função diminuir o impacto, promover a adaptação entre as faces articulares do fêmur e da tíbia. Melhoram assim a congruência das superfícies articulares promovendo a estabilidade. Pode danificar.se em uma única lesão traumática ou degradar-se com o tempo por meio de mini traumas. Na corrida de rua, no entanto, as lesões meniscais estão ligadas ao micro-trauma de repetição. Pessoas mais velhas, que correm em superfícies irregulares ou que fazem curvas repentinas e paragens bruscas correm o maior risco de danos ao menisco. Uma pessoa com um menisco rompido pode sentir dor, tumefacção e rigidez no joelho. Além disso, o joelho pode ceder ou ficar com a amplitude articular comprometida se um pequeno fragmento do menisco roto impedir o movimento articular.

Osteoartrose do joelho: As alterações degenerativas das articulações, vulgo artrose, iniciam-se com perda da massa condral que ao levarem à deficiente absorção do impacto proporcionam um aumento de conflito osseo das facetas articulares, com focos de edema, perda da trabeculação cortical e trabecular e consequente formação de geodes, micro fraturas com irregularidade das superficies corticais e formação de excrecências ósseas – osteofitos. Estes fenómenos têm uma evolução lenta mas levam com o tempo à incapacidade de marcha se não houver intervenção médica. Ainda está presente a discussão se a corrida regular causa ou não osteoartrite do joelho. No entanto pessoas que já têm osteoartrite do joelho esta actividade pode acelerar o desgaste da articulação.

Correr regularmente como actividade gímnica oferece outros benefícios à saúde, como controle de peso, o que supera os danos potenciais de artrite nos joelhos. A artrite do joelho pode fazer com que o corredor sinta dores nos joelhos durante um treino ou após um treino. Podem ficar tumefactos e doridos ao agachar, subir escadas e após inatividade prolongada, como ao sair da cama pela manhã.

Os joelhos sofrem pressão igual a aproximadamente 3 vezes o peso do corpo ao caminhar e aproximadamente 5 vezes o peso do corpo ao correr. Em outras palavras, uma pessoa que pesa 68 Kg coloca cerca de 340 Kg de pressão no joelho ao pousar cada passada de corrida.

Não surpreende por isso, ser o joelho a articulação lesionada com mais frequência em corredores e não corredores.

Objective:

Evaluation Of Tendon Morphology By Ultrasonography In Treatment Of Recalcitrant Tennis Elbow By Autologous Platelet Rich Plasma

Objective Evaluation Of Tendon Morphology By Ultrasonography In Treatment Of Recalcitrant Tennis Elbow By Autologous Platelet Rich Plasma

                           Jain S, Banodha L, Kelkar R, Gautam V

Investigation preformed at Department of Orthopaedics, Mahatma Gandhi Memorial Medical College & Maharaja Yashwantrao Hospital, Indore (M.P.), India.

Abstract

Background: Traditional therapies of tennis elbow have shown inconsistent outcomes as they do not deal with poor tendon healing properties secondary to poor vascularization. Local platelet rich plasma injections, which provide locally high concentration of growth factors, have shown its efficacy in treatment of tennis elbow on a subjective basis only.

Material and methods: We tried to measure the efficacy of locally injected autologous PRP, subjectively by functional oxford elbow score and pain score as well as objectively by ultrasonographic evaluation of the morphologic changes (focal hypoechoic, edema, tendon thickness, fraying, tear, cortical erosion, calcification) in common extensor origin in 30 patients with mean age of 39.3 years of recalcitrant tennis elbow.

Results: The mean pain VAS Score improved from 7.7 before injection to 1.8 at final follow up i.e. after 6 months post injection. The Oxford elbow score improved from a mean of 19.2 prior to treatment to 41.3 after the injection at final follow up. 6 months post injection ultrasonography of the involved elbow showed decrease in focal hypoechoic, decreased edema, and improvement in thickness of the tendon and healing of the tear at the origin site.

Conclusion: This study confirms that local PRP by supplying growth factors helps to enhance the stromal and mesenchymal stem cell proliferation and increases tendon vascularity and prevents angiofibroblastic degeneration and thus improves tendon repair and healing property by releasing growth factors and increasing vascularity, which can be documented by improved tendon morphology.

Keywords: Tennis elbow, Platelet rich plasma, Ultrasonography

Notas

A epicondilite lateral, também conhecida como cotovelo do tenista, é uma condição comum que acomete de 1 a 3% da população. O termo epicondilite sugere inflamação, embora a análise histológica tecidual não demonstre um processo inflamatório. A estrutura acometida com mais frequência é a origem do tendão extensor radial curto do carpo e o mecanismo de lesão está associado à sua sobrecarga ou movimentos repetitivos.
O tratamento incruento é o de escolha e inclui:

- repouso,

- fisioterapia,

- infiltração com cortisona, 

-plasma rico em plaquetas

ou ainda em situações mais graves o plasma rico em plaquetas activado, técnica Goldic 

- e a utilização de imobilização específica.

O tratamento cirúrgico é recomendado quando persistem impotência funcional e dor. Tanto a técnica cirúrgica aberta quanto a artroscópica com ressecção da área tendinosa degenerada apresenta bons resultados na literatura.

Does platelet-rich plasma for the knee work?

Does platelet-rich plasma for the knee work?

Last reviewed

Reviewed by William Morrison, MD

Athletes such as Tiger Woods and Rafael Nadal are rumored to have undergone a relatively new treatment that involves injections of platelet-rich plasma. Proponents say the therapy offers cutting-edge treatment for previously debilitating injuries, including painful knee problems due to osteoarthritis.

Contents of this article:

1. What is platelet-rich plasma?
2. Protein-rich plasma knee treatment vs. platelet-rich plasma?
3. Does platelet-rich plasma knee treatment work?
4. What to expect during and after treatment

What is platelet-rich plasma?

Platelet rich blood plasma from the patient will be injected into the knee as part of the treatment.

Platelets in the blood are what help with blood clotting, they also contain growth factors that may help healing.

A knee brace or splint may be recommended after platelet-rich blood plasma treatment, alongside rest and gentle physical therapy.

Intraneural Platelet-Rich Plasma Injections for the Treatment of Radial Nerve Section: A Case Report

Journal of Clinical Medicine 2018, 7(2), 13; doi:10.3390/jcm7020013

Case Report

Intraneural Platelet-Rich Plasma Injections for the Treatment of Radial Nerve Section: A Case Report

Unai García de Cortázar 1, Sabino Padilla 2, Enrique Lobato 1, Diego Delgado 3 and Mikel Sánchez 3,4,*

1

Service of Orthopedic Surgery and Traumatology, Basurto Hospital, 48013 Bilbao, Spain

2

University Institute for Regenerative Medicine and Oral Implantology-UIRMI, University of the Basque Country, Vitoria, 01007 Vitoria-Gasteiz, Spain

3

Advanced Biological Therapy Unit, Hospital Vithas San José, 01008 Vitoria-Gasteiz, Spain

4

Arthroscopic Surgery Unit, Hospital Vithas San José, 01008 Vitoria-Gasteiz, Spain

Received: 5 December 2017 / Accepted: 16 January 2018 / Published: 29 January 2018

Abstract

1. Introduction

The radial nerve is the most frequently injured nerve in the upper extremity, especially in patients with multiple injuries [1]. It may be damaged by several mechanisms, such as direct nerve trauma, complex humerus fracture, compression, (i.e., Saturday night palsy), iatrogenic lesions, neuritis or, more rarely, tumors and lead ingestion [2]. Clinically, these patients present a wide range of symptoms from weakness to complete paralysis of the elbow, forearm, wrist, finger, and thumb extension, failure of forearm supination, thumb abduction, and triceps reflex abolition, with or without sensory deficit in the back side of the forearm and in back and radial side of the hand. The loss of active extension of the wrist removes the mechanical advantage to grab things and grip hard.

Numerous options in treatment have been described for radial nerve injury. The approach may depend on the cause of the injury, and observation is often enough in diagnosing most cases, with a spontaneous resolution of the palsy [3]. However, in severe situations, treatment includes primary repair, neurolysis, nerve grafts, or tendon transfers. A few years ago, tendon transfers were the predominant reconstructive option for radial nerve injuries, but this choice is often technically difficult, and the outcomes are not always satisfactory [2,3,4]. In recent years, evidence has been accumulating in both preclinical and clinical settings indicating that platelet-rich plasma (PRP) products, and fibrin scaffolds obtained from this technology hold therapeutic potential as a neuroprotective, neurogenic, and neuroinflammatory modulator system [5,6,7], and an enhancer of sensory and motor functional nerve-muscle unit recovery [8,9,10,11,12]. PRP is a liquid-to-gel fibrin matrix injectable scaffold that, once applied on the injured area, either as a filler, suturable membrane, or scaffold tissue, fibrinolysis breaks the fibrin down, thereby releasing cell signaling molecules such as nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), fibrin, fibronectin and vitronectin.These biomolecules have been shown to be instrumental instructive and permissive agents involved in the control of stem cell-like myelinating Schwann Cells (SC) activation, macrophage polarization, as well as in the active resolution of inflammation, angiogenesis, and fibrogenesis, thereby acting as key drivers of nerve function recovery [5,11]. This manuscript describes the case of a patient who was treated for a traumatic radial nerve section 48 h after injury.

2. Case Report

2.1. Case Description

The study was conducted in accordance with the Declaration of Helsinki, and case report was approved by the Ethics Committee of Hospital Universitario Basurto (CS/UGA/1217, approved date: 21 December 2017). The patient was a healthy 27-year-old man with no history of interest to this report. He was a professional plumber, amateur cyclist, and snowboarder who, during an assault, suffered a deep and long cut (about 10 cm) with a knife in the cubital fossa of the right arm, extending proximally towards the radial region. Immediately after the knife cut, the patient had lost full functional ability to recruit the dependent muscles of the radial nerve, and suffered dysesthesia in the region. Due to the alarming clinical extent of the cut, the patient went to the emergency department of the nearest hospital. Upon arrival, four hours after the injury, the patient was taken to the operating room and under general anesthesia, surgical revision of the wound was conducted. After revision, the entire section of the radial nerve, distal tendon and muscle belly of the biceps brachii, and a section of the sensory branch of the musculocutaneous nerve were observed. No vascular damage was evident in the major vessels of the region. Next, labeling of proximal and distal ends of radial nerve with non-absorbable monofilament suture (polypropylene) was conducted. Moreover, an end-to-end suture of the distal tendon of biceps brachii was performed, which followed a postoperative period without incident, with progressive recovery of strength and mobility. The skin was provisionally closed with metal staples (Figure 1). Finally, the limb was immobilized by means of a dorsal plaster splint. After this emergency surgery, the patient was sent to his referral hospital in order to repair the lesions described previously.

Figure 1. First surgical revision of the wound. Section of the radial nerve, distal tendon and muscle belly of the biceps brachii. 1: distal end of the radial nerve; 2: proximal end of the radial nerve; 3: Lacertus fibrosus.

The patient came to our clinic 45 h after injury. The sensory examination showed hypoesthesia in all dependent musculocutaneous nerve areas and hypoesthesia with a feeling of numbness in the radial dependent region. Tinel’s sign was found in the suture zone without progression to the distal nerve. Manual muscle testing (MMT) was 0/5 for all dependent regions of the radial nerve distal to the injury, except for the common extensor muscle of fingers and for 5th finger extensor which was 1/5.

Forty-eight hours after injury the patient underwent general anesthesia, and a second wound review, where the previously-described injuries were observed. A reinforcing of the brachial biceps tendon suture was performed. An end-to-end suture of the radial nerve and of the sensory branch of musculocutaneous nerve was also conducted. The suture was done without a microscope so only an epineural suture was performed with non-absorbable Ethilon 8/0 suture. In addition, coverage of the nerve sutures was associated with vein grafts obtained from superficial veins of ipsilateral palmar wrist region. The skin was closed with metal staples and the member was immobilized with a posterolateral plaster splint.

Ten days after the second-look surgery, the patient reported good pain control without fever or systemic symptoms. Immobilization was removed, and a good evolution of the surgical wound was observed so the staples were removed, and the antibiotic treatment was halted. Physical examination did not reveal variations from before second surgery. The plaster splint was replaced with a thermoplastic splint in extension in order to begin assisted physiotherapy immediately by rehabilitation service. The patient underwent a rehabilitation program that included electrostimulation and specific therapy. This therapy consisted primarily in exercises, like stretching of the fingers and wrist, and motor skills with the hand. Despite the rehabilitation and a comprehensive monitoring program, functional progress was not satisfactory and there were no clinically-significant changes three months after the second surgery. Therefore, an electromyogram (EMG) was required, showing right radial nerve neurotmesis with no tendency to reinnervation.

Given the circumstances, it was decided to apply an intraneural ultrasound (US)-guided injection of PRP. The results observed in animal studies as well as in other similar cases and in prior orthopaedic experience using PRP were key in choosing this treatment [10,13].

2.2. Platelet-Rich Plasma Preparation

PRP was elaborated according to PRGF®-Endoret® technology (BTI Biotechnology Institute, Vitoria-Gasteiz, Spain). Briefly, a total of 36 ml of peripheral venous blood was withdrawn into 9-mL tubes containing 3.8% (w/v) sodium citrate. Blood was centrifuged at 580 g for eight minutes at room temperature. The upper volume of plasma, which contains a similar platelet count to that of peripheral blood, was drawn off and discarded in a collection tube. The 2-mL plasma fraction, located just above the sediment red blood cells, but not including the buffy coat, was collected in another tube and carried to the injection room ready for use. This plasma contains a moderate enrichment of platelets (two- to three-fold the platelet count of peripheral blood) with scarce leucocytes, being a P2-x-Bβ PRP according to the classification system proposed by DeLong et al. [14]. To initiate clotting, calcium chloride (10% w/v) was added to the liquid PRP aliquots just before injection. All procedures were performed under sterile conditions.

2.3. US-Guided Injection Technique

For each injection, US examination was carried out by an experienced radiologist together with the same orthopedic surgeon. First, the injured site was located and, because it seemed to have continuity, it was decided to perform the injection in the suture area. The injection was performed using a 22-gauge needle just below the probe to allow visualization of the needle and ensure an intraneural infiltration of the autologous preparation. Four milliliters of PRP was injected softly within the epineurium and also around the injured site (Figure 2). In total, five injections were performed, the first three with two-week intervals followed by two more injections two months after the first infiltration. The frequency of these injections rested on the clinical and EMG outcomes.

Figure 2. US-guided plasma rich in growth factors injection for the radial nerve. The procedure was performed in sterile conditions in an outpatient setting. The multi-frequency linear probe was aligned with the long axis of the radial nerve, and a 22-gauge needle (25 mm) was inserted into the radial nerve. The accuracy of platelet-rich plasma (PRP) infiltration was confirmed by direct visualization by US imaging.

2.4. Clinical Evolution after the First Injection

Three months after the first PRP injection the patient reported subjective clinical improvement in sensitivity and the MMT was 3/5 for all dependent regions of the radial nerve distal to the injury, except for the common extensor muscle of finger in brachiorradialis that was 1/5. Due to these encouraging results new infiltrations were applied.

Five months after the first injection, with a total of five intraneural PRP injections, EMG showed a right radial neuropathy with reinnervation in the muscle dependent on radial nerve below the elbow. At that time, the MMT had improved and presented 5/5 in the common extensor muscle of the finger, carpis radialis longus extensor, carpis radialis brevis extensor, digiti minimi extensor; 4/5 in the indicis extensor; and 2/5 in the brachiorradialis. Sensitivity demonstrated almost full recovery in the radial nerve distribution area. At that point, the patient started a new rehabilitation program that included activities that he performed at work, so he could achieve sufficient functionality to return to his profession. Fourteen months after the injury and 11 months after the first PRP injection, functional recovery was achieved. The EMG showed a complete reinnervation of the musculature dependent of the radial nerve (Figure 3).

Figure 3. Electromyographic control from surgery up to date. Three months after surgery (1); sSix months after surgery, three after first PRP injection (2); eight months after surgery, five after the first PRP injection (3); and one year after surgery, nine months after first PRP injection (4). EMG: electromyogram; PRP: platelet-rich plasma infiltrations.

3. Discussion

In the field of orthopedics and plastic surgery, the process of nerve regeneration and target organ reinnervation is a difficult challenge. Fueled by the drawbacks posed by autologous nerve autografts, several biomedical engineering strategies have recently emerged. These include nerve guidance conduits and scaffolds, which can incorporate and deliver neurotrophic factors and support cells into nerve guidance conduits or fibrin gels, and target organ stimulation through intramuscular injections of growth factors [5,11,15]. Nevertheless, these new strategies are infrequently used either as a main therapeutic approach or as an adjuvant for nerve regeneration. Research studies using PRP in animals and humans are encouraging [6,8,9,10,11,12,16]. Surgical procedures and results for nerve repair and their results are conditioned by several factors, such as the patient´s age, the cause and level of the lesion, associated injuries, duration of denervation, the length of the nerve defect, the type of repair, the use of electrophysiological recordings, and the surgeon´s experience [17]. The radial nerve functional recovery after five perineural and intraneural injections of PRP presented in this case report is consistent with the results published by other teams using PRP as a therapeutic tool to assist nerve repair [13,18,19,20,21,22], although some subtle differences in procedures are notable. In a case study from Kuffler et al., a long ulnar nerve gap 12 cm in length was bridged with autologous PRF as a filler in a collagen tube 3.25 years after an ulnar nerve trauma leading to recovery of both muscle and sensory function in a 58 year old patient [8]. Moreover, in a recent series of cases of surgical nerve repair, Kuffler et al. reported functional recovery in 18 patients under 58 years whose nerve gaps of 2–16 cm were treated with collagen tubes filled with PRP, 0.5–3 years after the traumatic injury [18]. No patients suffered adverse events. Two clinical trials using PRP as an adjuvant therapeutic tool to assist nerve surgery reported protective and clinical beneficial effects. Scala et al. applied PRP gel to the excision site and around facial nerve endings in eight patients with mixed tumors undergoing superficial parotidectomy [20]. In the same direction, Hibner et al. coated the pudendal nerve with PRP after pudendal neurolisis in 10 patients where transgluteal decompression of the pudendal nerve had failed [21]. Sanchez et al. and Malahias et al. applied the liquid dynamic fibrin formulation of PRP as an injectable adjuvant to treat common peroneal nerve palsy and carpal tunnel syndrome respectively, with successful nerve function recovery [13,22].

In the case reported here, the existence of associated nerve injuries has a negative effect in the postoperative recovery because of an increasing amount of scar tissue and extensive muscle involvement [23]. Furthermore, when the reparation is done later than 24 h from injury, it is always necessary to remove at least 1 mm of nerve stump [24]. The suture was performed 48 h after the damage, without microscope or intraoperative electrophysiological recordings. According to an algorithm for radial nerve reconstruction, a tension-free end-to-end repair of the radial nerve section was conducted, but without removing the nerve stump. Only an epineural suture was carried out, without joining the fascicles together. Owing to these procedural conditions, the postoperative evolution was not satisfactory, and three months after the surgery the patient presented no improvement in either sensory or motor function; muscle atrophy was emerging despite physiotherapy. At this point EMG study was requested and a right radial nerve neurotmesis was detected with no tendency to reinnervation. Based on results from the scientific literature and before considering other surgical options, such as neurolysis, nerve grafting, or even tendon transposition, we decided to use the PRP approach to create a favorable environment for nerve repair by injecting perineural and intraneural PRP. Once activated, it becomes a liquid, sponge-like, viscous and malleable dynamic and transient fibrin scaffold that fills the nerve gaps and adheres to ECM structures of the damaged tissue [25]. The suitability of PRP as a therapeutic tool is underpinned by its gradual and sustained release of growth factors and other molecular signals from the autologous platelet-rich plasma derived fibrin matrix, as well as its bioresorbable, biocompatible, versatile, and plastic properties. In contrast to a bolus delivery modality of GFs, which has been shown to be less efficacious in the repair process [26] tissue fibrinolysis mediates in PRP´s gradual and sustained release of several GFs and other biomolecules [27]. At present, 14 months after the injury and 11 months after the first PRP injection, functional recovery has been completed, with the exception of the brachiorradialis function that still presents a grade of three in manual muscle testing. The EMG shows a complete reinnervation in the musculature of the radial nerve dependent, with the exception of an injury focus on the exit branch to the brachiorradialis. The patient is satisfied with the result and he is able to practice his profession. Although this is an excellent result, it is reasonable to expect a spontaneous recovery without using PRP. However, the patient’s clinic and previous experience suggest that he would have presented a motor and sensory deficit, as he had prior to infiltrations [13]. Indeed, a better and faster clinical outcome might have been obtained by applying PRP infiltrations in the early phase, starting in the emergency room following the surgical process shown in the Sánchez et al. work on sheep [10].

The significant clinical outcome of this case report in parallel with the other results described here supports the therapeutic use of PRPs as versatile and safe biological products to be harnessed by surgeons and clinicians as an adjuvant therapeutic tool to enhance the robust intrinsic nerve repair processes, and overcome a post-traumatic and neuropathic inhibitory microenvironment by delivering neurotrophic and neurotropic factors. PRP may assist nerve conduit guidance and grafts as a filler, as a liquid in intraneural and perineural ultrasound-guided injections in nerve entrapments and fibrosis, and as a scaffold to bridge or wrap the injured nerve gap.

4. Conclusions

PRP infiltrations have the potential to enhance the healing process of radial nerve palsy. This case report suggests the therapeutic potential of this technology for traumatic peripheral nerve palsy, as well as the apt utility of US-guided PRP injections.

Author Contributions

Unai García de Cortázar, Sabino Padilla, Diego Delgado and Mikel Sánchez contributed to the conception and design. Unai García de Cortázar and Enrique Lobato, contributed to the provision of data. All authors contributed to analysis and interpretation of the data. All authors contribute to drafting, critical revision and final approval of the article.

Conflicts of Interest

Sabino Padilla declares the following competing financial interest: Sabino Padilla is scientist at BTI Biotechnology Institute, a dental implant company that investigates the fields of oral implantology and PRGF-Endoret technology.

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Biomed Res Int. 2016;2016:9103792. doi: 10.1155/2016/9103792. Epub 2016 Aug 16.

PRP Treatment Efficacy for Tendinopathy: A Review of Basic Science Studies.

Zhou Y1, Wang JH2.

Author information

Abstract

Platelet-Rich Plasma (PRP) has been widely used in orthopaedic surgery and sport medicine to treat tendon injuries. However, the efficacy of PRP treatment for tendinopathy is controversial. This paper focuses on reviewing the basic science studies on PRP performed under well-controlled conditions. Both in vitro and in vivo studies describe PRP's anabolic and anti-inflammatory effects on tendons. While some clinical trials support these findings, others refute them. In this review, we discuss the effectiveness of PRP to treat tendon injuries with evidence presented in basic science studies and the potential reasons for the controversial results in clinical trials. Finally, we comment on the approaches that may be required to improve the efficacy of PRP treatment for tendinopathy.

owa Orthop J. 2012;32:150-63.

Evaluation of the effects of platelet-rich plasma (PRP) therapy involved in the healing of sports-related soft tissue injuries.

Middleton KK1, Barro V, Muller B, Terada S, Fu FH.

Author information

Abstract

Musculoskeletal injuries are the most common cause of severe long-term pain and physical disability, and affect hundreds of millions of people around the world. One of the most popular methods used to biologically enhance healing in the fields of orthopaedic surgery and sports medicine includes the use of autologous blood products, namely, platelet rich plasma (PRP). PRP is an autologous concentration of human platelets to supra-physiologic levels. At baseline levels, platelets function as a natural reservoir for growth factors including platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor-beta 1 (TGF-β1), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), hepatocyte growth factor (HGF), and insulin-like growth factor (IGF-I). PRP is commonly used in orthopaedic practice to augment healing in sports-related injuries of skeletal muscle, tendons, and ligaments. Despite its pervasive use, the clinical efficacy of PrP therapy and varying mechanisms of action have yet to be established. Basic science research has revealed that PRP exerts is effects through many downstream events secondary to release of growth factors and other bioactive factors from its alpha granules. These effects may vary depending on the location of injury and the concentration of important growth factors involved in various soft tissue healing responses. This review focuses on the effects of PrP and its associated bioactive factors as elucidated in basic science research. Current findings in PRP basic science research, which have shed light on its proposed mechanisms of action, have opened doors for future areas of PrP research.

PMC3565396

Free PMC Article

J Am Acad Orthop Surg. 2013 Dec;21(12):739-48. doi: 10.5435/JAAOS-21-12-739.Platelet-rich plasma in orthopaedic applications: evidence-based recommendations for treatment. Hsu WK, Mishra A, Rodeo SR, Fu F, Terry MA, Randelli P, Canale ST, Kelly FB.

Abstract

Autologous platelet-rich plasma (PRP) therapies have seen a dramatic increase in breadth and frequency of use for

orthopaedic conditions in the past 5 years. Rich in many growth factors that have important implications in healing, PRP

can potentially regenerate tissue via multiple mechanisms. Proposed clinical and surgical applications include spinal

fusion, chondropathy, knee osteoarthritis, tendinopathy, acute and chronic soft-tissue injuries, enhancement of healing

after ligament reconstruction, and muscle strains. However, for many conditions, there is limited reliable clinical

evidence to guide the use of PRP. Furthermore, classification systems and identification of differences among products

are needed to understand the implications of variability.

Comment in

PRP. [J Am Acad Orthop Surg. 2014]

Platelet-rich plasma in orthopaedic applications: evidence-based recommendations for treatment. [J Am Acad Orthop Surg. 2014].