Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

https://escholarship.org/content/qt76m4g3q5/qt76m4g3q5.pdf?t=oe66jy

Repair and tissue engineering techniques for articular cartilage

Purpose: To determine (1) whether platelet-rich plasma (PRP) injection significantly improves validated patient-reported outcomes in patients with symptomatic knee osteoarthritis (OA) at 6 and 12 months postinjection, (2) differences in outcomes between PRP and corticosteroid injections or viscosupplementation or placebo injections at 6 and 12 months postinjection, and (3) similarities and differences in outcomes based on the PRP formulations used in the analyzed studies. Methods: PubMed, Cochrane Central Register of Controlled Trials, SCOPUS, and Sport Discus were searched for Englishlanguage, level I evidence, human in vivo studies on the treatment of symptomatic knee OA with intra-articular PRP compared with other options, with a minimum of 6 months of follow-up. A quality assessment of all articles was performed using the Modified Coleman Methodology Score (average, 83.3/100), and outcomes were analyzed using 2-proportion z-tests. Results: Six articles (739 patients, 817 knees, 39% males, mean age of 59.9 years, with 38 weeks average follow-up) were analyzed. All studies met minimal clinical important difference criteria and showed significant improvements in statistical and clinical outcomes, including pain, physical function, and stiffness, with PRP. All but one study showed significant differences in clinical outcomes between PRP and hyaluronic acid (HA) or PRP and placebo in pain and function. Average pretreatment Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were 52.36 and 52.05 for the PRP and HA groups, respectively (P ¼ .420). Mean post-treatment WOMAC scores for PRP were significantly better than for HA at 3 to 6 months (28.5 and 43.4, respectively; P ¼ .0008) and at 6 to 12 months (22.8 and 38.1, respectively; P ¼ .0062). None of the included studies used corticosteroids. Conclusions: In patients with symptomatic knee OA, PRP injection results in significant clinical improvements up to 12 months postinjection. Clinical outcomes and WOMAC scores are significantly better after PRP versus HA at 3 to 12 months postinjection. There is limited evidence for comparing leukocyte-rich versus leukocyte-poor PRP or PRP versus steroids in this study. Level of Evidence: Level I, systematic review of Level I studies.

Efficacy of Intra-articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Systematic Review

Background:Elbow tenderness and pain with resisted wrist extension are common manifestations of lateral epicondylar tendinopathy, also known as tennis elbow. Previous studies have suggested platelet-rich plasma (PRP) to be a safe and effective therapy for tennis elbow.Purpose:To evaluate the clinical value of tendon needling with PRP in patients with chronic tennis elbow compared with an active control group.Study Design:Randomized controlled trial; Level of evidence, 2.Methods:A total of 230 patients with chronic lateral epicondylar tendinopathy were treated at 12 centers over 5 years. All patients had at least 3 months of symptoms and had failed conventional therapy. There were no differences in patients randomized to receive PRP (n = 116) or active controls (n = 114). The PRP was prepared from venous whole blood at the point of care and contained both concentrated platelets and leukocytes. After receiving a local anesthetic, all patients had their extensor tendons needled with or without PRP. Patients ...

Efficacy of Platelet-Rich Plasma for Chronic Tennis Elbow: A Double-Blind, Prospective, Multicenter, Randomized Controlled Trial of 230 Patients

https://www.oarsijournal.com/article/S1063-4584(13)00903-5/pdf

Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: a review

Background:Leukocyte-poor platelet-rich plasma (LP-PRP) is hypothesized to be more suitable for intra-articular injection than leukocyte-rich PRP (LR-PRP) in the treatment of knee osteoarthritis.Purpose:To compare clinical outcomes and rates of adverse reactions between LP-PRP and LR-PRP for this application.Study Design:Meta-analysis.Methods:The MEDLINE, EMBASE, and Cochrane databases were reviewed. The primary outcome was the incidence of local adverse reactions. Secondary outcomes were the changes in International Knee Documentation Committee (IKDC) subjective score and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score between baseline and final follow-up measurements. A Bayesian network meta-analysis was performed, with a post hoc meta-regression to correct for baseline differences in WOMAC scores. Treatment rankings were based on surface under the cumulative ranking (SUCRA) probabilities.Results:Included in the analysis were 6 randomized controlled trials (evidence level 1)...

Effect of Leukocyte Concentration on the Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis

Platelet Rich Plasma (PRP), a blood-derived product rich in growth factors, is a promising treatment for cartilage defects but there is still a lack of clinical evidence. The aim of this study is to show, through a randomized double blind prospective trial, the efficacy of this procedure, by comparing PRP to Hyaluronic Acid (HA) injections for the treatment of knee chondropathy or osteoarthritis (OA). 109 patients (55 treated with HA and 54 with PRP) were treated and evaluated at 12 months of follow-up. The patients were enrolled according to the following inclusion criteria: age> 18 years, history of chronic (at least 4 months) pain or swelling of the knee and imaging findings of degenerative changes of the joint (Kellgren-Lawrence Score up to 3). A cycle of 3 weekly injections was administered blindly. All patients were prospectively evaluated before and at 2, 6, and 12 months after the treatment by: IKDC, EQ-VAS, TEGNER, and KOOS scores. Range of motion and knee circumference changes were measured over time. Adverse events and patient satisfaction were also recorded. Only minor adverse events were detected in some patients, such as mild pain and effusion after the injections, in particular in the PRP group, where a significantly higher post-injective pain reaction was observed (p=0.039). At the follow-up evaluations, both groups presented a clinical improvement but the comparison between the two groups showed a not statistically significant difference in all scores evaluated. A trend favorable for the PRP group was only found in patients with low grade articular degeneration (Kellgren-Lawrence score up to 2). Results suggest that PRP injections offer a significant clinical improvement up to one year of follow-up. However, conversely to what was shown by the current literature, for middle-aged patients with moderate signs of OA, PRP results were not better than those obtained with HA injections, and thus it should not be considered as first line treatment. More promising results are shown for its use in low grade degeneration, but they still have to be confirmed.

/pdf/platelet-rich-plasma-vs-hyaluronic-acid-to-treat-knee-58ryznyxmk.pdf

Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial

Background:Osteoarthritis (OA) is a common disease that will affect almost half the population at some point in their lives through pain and decreased functional capacity. New nonoperative options are being proposed to treat earlier stages of joint degeneration to provide symptomatic relief and delay surgical intervention.Purpose:To evaluate the benefit provided by platelet-rich plasma (PRP) injections to treat knee joint degeneration in comparison with hyaluronic acid (HA), the most common injective treatment currently adopted for this condition.Study Design:Randomized controlled trial; Level of evidence, 1.Methods:A total of 443 patients were screened, and 192 of them were enrolled in the study according to the following inclusion criteria: (1) unilateral symptomatic knee with history of chronic pain (at least 4 months) or swelling and (2) imaging findings of degenerative changes (Kellgren-Lawrence score of 0-3 at radiographs or MRI evidence of degenerative chondropathy). Patients underwent 3 weekly int...

Platelet-Rich Plasma Intra-articular Knee Injections Show No Superiority Versus Viscosupplementation: A Randomized Controlled Trial

Purpose
The aim of this review was to analyze the available evidence on the clinical application of this biological approach for the injective treatment of cartilage lesions and joint degeneration, together with preclinical studies to support the rationale for the use of platelet concentrates, to shed some light and give indications on what to treat and what to expect from intra-articular injections of platelet-rich plasma (PRP).

/pdf/platelet-rich-plasma-why-intra-articular-a-systematic-review-3soc7wm1jd.pdf

Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration

Purpose: the aim of this study was to describe the clinical results obtained after intra-articular injection of a leukocyte-poor platelet-rich plasma (PRP) preparation for the treatment of knee osteoarthritis (OA).
Methods: forty-five patients (mean age: 59 years, mean BMI: 27) were included and treated with a cycle of three weekly injections of autologous conditioned plasma. Six patients were affected by bilateral symptomatic OA, therefore 51 knees in total were treated.
The patients were divided into two groups: those affected by early/moderate OA and those affected by severe OA. The patients were submitted to baseline evaluation and evaluation after a mean follow-up of 14.5 months (range: 6-24 months), performed using the following outcome measures: IKDC-subjective, EQ-VAS, Tegner, and KOOS scores. Adverse events and patient satisfaction were also recorded.
The results in the two groups of patients (“early/moderate” vs “severe OA”) were analyzed separately.
Results: the overall clinical outcome was positive and the treatment proved to be safe. In the “early/moderate OA” group, the IKDC-subjective score increased from 36.4 at the baseline evaluation to 57.3 at the follow-up (p<0.0005) and a similar trend was shown by the EQ-VAS, Tegner, and KOOS scores. Although an improvement was also recorded in the “severe OA” group, the clinical outcome of the patients in this group was significantly poorer and they reported less benefit. In the “early/moderate OA” group, BMI and longer symptom duration before treatment were found to be correlated with clinical outcome.
Conclusions: PRP injections are capable of reducing pain and improving knee functional status at shortterm follow-up. The patients with a lower degree of joint degeneration were the best responders, whereas in severe osteoarthritic knees this biological treatment, used as a “salvage procedure”, produced a less favorable outcome.
Level of evidence: level IV; therapeutic case series.

/pdf/leukocyte-poor-prp-application-for-the-treatment-of-knee-2z0yw0qgsw.pdf

Leukocyte-poor PRP application for the treatment of knee osteoarthritis.

Bone possesses the intrinsic regeneration capacity as part of the repair process in response to injury, during skeletal development or continuous remodeling throughout adult life.
 However, some complex clinical conditions require bone regeneration in too large quantity, and tissue engineering approach was developed to favor the regeneration of a new functional tissue. Mesenchymal stem cells (MSCs) have emerged as a promising alternative to the traditional surgical techniques.
 The purpose of this mini-review is to investigate the role of MSCs in clinical practice for bone regeneration, documenting the state of art and indentifying future research directions.
 We performed a search of the literature on PUBMED database between 2001 and 2011 using the key words “MSC and bone regeneration”. Inclusion criteria were clinical studies regarding the use of MSC in bone regeneration, for both bone repair
 and metabolic bone diseases, and in English language.
 References from selected papers were also screened. Our search resulted in 516 articles. Among these a total of 18 articles were included: 12 case series, 5 case reports and 1 comparative studies.
 MSCs represent an exciting and promising stem cell population for regeneration of bone in skeletal diseases, especially when tissue engineering or biomaterials are applied. However, literature results are limited, because of the small number and the low quality of trials, the lack of controls and the short follow-up. Researchers have to perform more high quality studies in order to document results and increase the potential of MSCs use in clinical practice, to develop a minimally invasive treatment to favor high quality bone tissue regeneration

Maria Letizia Merli

Papers

Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial

Platelet-Rich Plasma Intra-articular Knee Injections Show No Superiority Versus Viscosupplementation: A Randomized Controlled Trial

Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration

Leukocyte-poor PRP application for the treatment of knee osteoarthritis.

Bone regeneration with mesenchymal stem cells