2. Universidad Cardenal Herrera-CEU

The purpose of this study was to perform a histological and biochemical evaluation of the influence of plasma rich in growth factors (PRGF) on muscle regeneration process after a surgically induced grade II muscle laceration. A randomized, single blind, controlled experimental research was conducted including twenty-one adult healthy sheep, randomly divided in three groups (n = 7). A grade II surgical section was performed in the biceps femoris muscle of both hindlimbs. After two days (basal time), intralesional infiltration of autologous PRGF or Saline solution was randomly administered in both hindlimbs. Treatment was repeated once a week. Animal groups were euthanized at 1 (T1), 2 (T2) or 4 (T4) weeks. Histological assessment showed that PRGF intralesional injection induced a significant decrease of inflammatory cells density, significant higher centrally nucleated fibers percentage and significantly smaller fibrotic areas compared to Saline-treated muscles at T1, T2 and T4. Also, lower vascular density, with lower capillaries cross-sectional area, in PRGF group compared to Saline was observed. Biochemical analysis revealed a significant higher expression level of MYOD1, MYF5 and MYOG genes in PRGF groups at T1 compared to Saline treated muscles. At ultrastructural level, PRGF groups presented scarce edema and loss of connective tissue structure, as well as higher mitochondrial density adequately associated to the sarcomere unit in contrast to the Saline group. In conclusion, histological, biochemical, and ultrastructural results showed that PRGF treatment improved muscle regeneration process leading to more mature histological aspect in newly formed muscle tissue after a surgically induced grade II muscle injury.

Osteoarthritis (OA) is the most common articular disease in adults and has a current prevalence of 12% in the population over 65 years old. This chronic disease causes damage to articular cartilage and synovial joints, causing pain and leading to a negative impact on patients’ function, decreasing quality of life. There are many limitations regarding OA conventional therapies—pharmacological therapy can cause gastrointestinal, renal, and cardiac adverse effects, and some of them could even be a threat to life. On the other hand, surgical options, such as microfracture, have been used for the last 20 years, but hyaline cartilage has a limited regeneration capacity. In recent years, the interest in new therapies, such as cell-based and cell-free therapies, has been considerably increasing. The purpose of this review is to describe and compare bioregenerative therapies’ efficacy for OA, with particular emphasis on the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). In OA, these therapies might be an alternative and less invasive treatment than surgery, and a more effective option than conventional therapies.

Traditionally, canine degenerative lumbosacral stenosis (DLS) has been defined as a multifactorial syndrome characterized by lumbosacral pain triggered by the compression of the nerve rootlets of the cauda equina. There is still no consensus on the treatment of this condition, probably because there are a plethora of possible causes. In addition to compression, inflammation is a very important factor in the physiopathology of the disorder. Platelet-rich plasma (PRP) consists of an increased concentration of autologous platelets suspended in a small amount of plasma. Platelets are a source of several growth factors. Growth factors were shown to help in wound healing and biological processes, such as chemotaxis, neovascularization and synthesis of extracellular matrix, and growth factors were used to improve soft tissue healing and bone regeneration. PRP also facilitates the restoration of the structural integrity of the affected anatomy. Fourteen dogs diagnosed with DLS were treated with three epidural injections of PRP on days 0, 15 and 45. All dogs showed clinical improvement 3 months after the initial treatment. Gait was also objectively assessed by means of the use of force platform analysis before and after treatment, showing significant improvement. The results show that PRP may provide a good alternative to other nonsurgical treatments, such as prednisolone epidural injection.

The purpose of this study is to evaluate the efficiency of local platelet-rich plasma (PRP) injection as an adjuvant treatment after carpal ligament release. We conducted a prospective randomized, tripleblinded, controlled trial. Fifty participants with mild to extreme carpal tunnel syndrome (CTS) were randomly assigned either to the PRP (n = 25) or the platelet-poor plasma (PPP, n = 25) group. After performing open surgical release of the carpal ligament, the inside of the carpal tunnel was irrigated with 3 mL of PRP or PPP according to each participant’s group allocation. The primary outcome was hand grip strength (HGS). Secondary outcomes were the time taken off work after surgery (in days) and scores on the Wong–Baker Faces Scale, Boston Carpal Tunnel Questionnaire, and Southampton Wound Assessment Scale. We evaluated patients before treatment and at 6-weeks. As expected, the pain levels, symptom severity, and functional status improved in all the patients after surgery. However, intragroup analysis revealed that only the participants in the PRP group had regained their pre-operative HGS levels at 6-weeks follow-up. These findings indicate that PRP is an effective adjuvant treatment in patients with mild to severe CTS who require surgery.

Osteoarthritis (OA) is one of the most significant joint diseases worldwide. There are di erent therapies for OA treatment, and a relatively new strategy is the use of plasma rich in growth factors (PRGF), a platelet rich plasma (PRP) derivative. The objective of this study was to objectively assess the e cacy and duration of the e ect of an intraarticular injection of PRGF and a combination of PRGF + physical therapy. The objective assessment was provided using a force platform. The obtained parameters were peak vertical force (PVF) and vertical impulse (VI). A total of 24 dogs with lameness and pain associated to OA attributable to bilateral hip dysplasia were included in the study. Animals were divided into two study groups and evaluated at baseline and at 30, 90, and 180 days after intraarticular PRGF or PRGF + physical therapy. Significant di erences were observed at every checkpoint with respect to basal time in both groups. However, after 180 days, the PRGF group showed a decrease in PVF and VI with respect to the values obtained at 90 days. However, the PRGF + physical therapy group maintained increased values of both PVF and VI values during the 180-day study period.

The role of platelet-rich plasma (PRP) in promoting the healing of bone fractures has notyet been clearly stated. The aim of this prospective clinical study was to evaluate the effectiveness ofplasma rich in growth factors (PRGF, a PRP derivate) in the treatment of naturally-occurring bonefractures in dogs. With this objective, sixty-five dogs with radius/ulna or tibia/fibula bone fractureswere randomly divided into two groups (PRGF and saline solution (SS) groups) and checked atdays 0, 7, 14, 21, 28, 35, 42, 49, 56, 60, 63, 70, 120, and 180. All the fractures were treated with anexternal skeletal fixation, and pain was controlled with Carprofen. Healing was evaluated by physicalexamination, limb function, radiography, and by a Likert-type owner satisfaction questionnaire.A faster fracture healing was observed in the PRGF group, with statistically significant differenceswith respect to the SS group. Swelling at the fracture site was significantly greater at day 14 and28 in animals injected with PRGF, and more pain on palpation was found in the area at day 28.The injection of PRGF in acute bone fractures accelerates bone healing.

To assess the biomechanical effects of intra-tendinous injections of PRGF on the healing Achilles tendon after repair in a sheep model. Thirty sheep were randomly assigned into one of the six groups depending on the type of treatment 10 received (PRGF or placebo) and survival time (2, 4 and 8 weeks). The Achilles tendon injury was repaired by suturing the tendinous edges employing a three-loop pulley pattern. A trans-articular external fixation system was then used for immobilization. The PRGF or placebo was administered on a weekly basis completing a maximum of 3 infiltrations. The force, section and tension values were compared between the operated and healthy Achilles tendons across all groups. The PRGF-treated tendons had higher force at eight weeks compared with the placebo group (p=0.007). Between two and four weeks, a significant increase in force in both the PRGF-treated tendon (p=0.0027) and placebo group (p=0.0095) occurred. No significant differences were found for section ratio between PRGF-treated tendons and the placebo group for any of the time periods evaluated. At 2 weeks PRGF-treated tendons had higher tension ratio compared to placebo group tendons (p=0.0143). Both PRGF and placebo treatments significantly improved the force (p<0.001 and p=0.0095, respectively) and tension (p=0.009 and p=0.0039, respectively) ratios at 8 compared to 2 weeks. The application of PRGF increases Achilles tendon repair strength at 8 weeks compared to the use of placebo. The use of PRGF does not modify section and tension ratios compared to placebo at 8 weeks. The tension ratio progressively increases between two and eight weeks compared with the placebo. PRGF can be used in the clinical setting as a complementary therapy to improve the repair strength of acute Achilles tendon ruptures.

A potential relationship between an increased risk of cancer and increased levels of serum insulin-like growth factor-1 (IGF-1), and presence of cancer and high levels of C-reactive protein (CRP) has been previously reported. This study evaluated the influence of a single intramuscular injection of plasma rich in growth factors (PRGF) on serum concentrations of IGF-1 and CRP in dogs. Two groups of eight healthy beagles were injected with two different doses of PRGF in lumbar muscles. For each treatment, IGF-1 and CRP were analysed from blood samples obtained at baseline and the following three days post injection. No differences were found when IGF-1 and CRP were compared among times in the two protocols. Local application of PRGF at clinical doses did not cause significant changes in systemic concentrations of IGF-1 or detectable inflammation.

Tendon injuries are the most frequent musculoskeletal problems, constituting 30–50% of all sport-related lesions. Efficient handling of early stage tendon injury and healing can accelerate tendon repair as well as improve the quality of newly formed tendons. Plasma rich in growth factors (PRGF) is an autologous biological therapy that has been proposed to treat tendon injuries. To elucidate the effect of this treatment on the early stage of tendon healing, 14 sheep were used to perform the present study. The right Achilles tendon was surgically severed and repaired with sutures. Seven animals were treated with PRGF and the other seven with saline solution after surgical tendon reconstruction. Tendons were ultrasound-guide infiltrated 1 week after the induced injury. Two weeks later, the sheep were euthanized and histochemical and immunohistochemical analyses were performed. The tendons with PRGF showed reduced infiltration of inflammatory cells compared to those treated with saline solution. Analysis of the blood vessels, morphometric data of fibroblast nuclei, and collagen fibres in the extracellular matrix did not show statistical differences between groups. These findings suggest the important role that PRGF therapy plays in the modulation of inflammatory response in Achilles tendon injuries, leading to acceleration of the tendon healing process, shortening the convalescence period.

The overall increase of chronic degenerative diseases associated with ageing makes wound care a tremendous socioeconomic burden. Thus, there is a growing need to develop novel wound healing therapies to improve cutaneous wound healing. The use of regenerative therapies is becoming increasingly popular due to the low-invasive procedures needed to apply them. Platelet-rich plasma (PRP) is gaining interest due to its potential to stimulate and accelerate the wound healing process. The cytokines and growth factors forming PRP play a crucial role in the healing process. This article reviews the emerging field of skin wound regenerative therapies with particular emphasis on PRP and the role of growth factors in the wound healing process.