Applying additional autologous platelet-rich fibrin matrix or serial platelet-rich plasma to microfracture technique increases the quality of the repaired cartilage.

PURPOSE: The aim of the present study is to investigate and compare the effects of biological adjuvants (platelet-rich plasma, platelet-rich fibrin matrix) and microfracture technique individually and in combination on full thickness chondral defects in a rabbit model. METHODS: A total of 60 New Zealand White rabbits were randomly divided into six groups according to treatment modality as follows: control (C), microfracture (MF), platelet-rich plasma (PRP), platelet-rich fibrin matrix (PRFM), platelet-rich fibrin matrix after microfracture (MF + PRFM) and platelet-rich plasma after microfracture (MF + PRP) groups. The cartilage repair tissue was assessed histologically via International Cartilage Repair Score (ICRS) and macroscopically via ICRS macroscopic assessment scale. RESULTS: It was shown that overall macroscopic scores of the groups with MF were higher than those of the groups without MF. The cell morphology observed in the defect areas was mostly characterized with non-chondrocyte cells in the groups without MF, whereas chondrocyte cells mostly prevailed in the groups with MF. There was a greater integration through the cartilage-like tissue in the MF + PRP and MF + PRFM groups. The control group showed either fissures or fissures partially filled with fibrous tissue. When the groups were individually examined, there were statistically significant differences between the control and MF groups (p = 0.002), between the control and MF + PRFM groups (p = 0.001), between the control and MF + PRP groups (p < 0.001), between the PRFM and MF + PRFM groups (p = 0.014) and between the PRFM and MF + PRP (p = 0.023) groups in terms of histological evaluation scores. CONCLUSION: The application of PRP and PRFM in combination with MF treatment exhibited a positive impact on the repair and restoration of cartilage, and produced better outcomes than the individual use of PRP and PRFM. Nevertheless, in the treatment of full thickness chondral defects, the use of PRFM injection is recommended, which is performed intraoperatively at a single time and with no difficulty of repeating after surgery, instead of serial PRP injections based on the macroscopic and histological results obtained in the present study indicating that there was no significant difference between the use of these two adjuvants.

An encapsulated fibrin-based bioartificial tissue construct with integrated macrovessels, microchannels, and capillary tubes.

Facilitating sufficient nutrient and oxygen supply in large-scale bioartificial constructs is a critical step in organ bioengineering. Immediate perfusion not only depends on a dense capillary network, but also requires integrated large-diameter vessels that allow vascular anastomoses during implantation. These requirements set high demands for matrix generation as well as for in vitro cultivation techniques and remain mostly unsolved challenges up until today. Additionally, bioartificial constructs must have sufficient biomechanical stability to withstand mechanical stresses during and after implantation. We developed a bioartificial tissue construct with a fibrin matrix containing human umbilical vein endothelial cells and adipose tissue-derived stem cells facilitating capillary-like network formation. This core matrix was surrounded by a dense acellular fibrin capsule providing biomechanical stability. Two fibrin-based macrovessels were integrated on each side of the construct and interconnected via four 1.2 mm thick microchannels penetrating the cellularized core matrix. After 4 days of perfusion in a custom-built bioreactor, homogeneous capillary-like network formation throughout the core matrix was observed. The fibrin capsule stabilized the core matrix and facilitated the generation of a self-supporting construct. Thus, the encapsulated fibrin tissue construct could provide a universal prevascularized matrix for seeding with different cell types in various tissue engineering approaches.

Differential effects of rat ADSCs encapsulation in fibrin matrix and combination delivery of BDNF and Gold nanoparticles on peripheral nerve regeneration.

BACKGROUND: Fibrin as an extracellular matrix feature like biocompatibility, creates a favorable environment for proliferation and migration of cells and it can act as a reservoir for storage and release of growth factors in tissue engineering. METHODS: In this study, the inner surface of electrospun poly (lactic-co-glycolic acid) (PLGA) nanofibrous conduit was biofunctionalized with laminin containing brain derived neurotrophic factor (BDNF) and gold nanoparticles in chitosan nanoparticle. The rats were randomly divided into five groups, including autograft group as the positive control, PLGA conduit coated by laminin and filled with DMEM/F12, PLGA conduit coated by laminin and filled with rat-adipose derived stem cells (r-ADSCs), PLGA conduit coated by laminin containing gold-chitosan nanoparticles (AuNPs-CNPs), BDNF-chitosan nanoparticles (BDNF-CNPs) and filled with r-ADSCs or filled with r-ADSCs suspended in fibrin matrix, and they were implanted into a 10 mm rat sciatic nerve gap. Eventually, axonal regeneration and functional recovery were assessed after 12 weeks. RESULTS: After 3 months post-surgery period, the results showed that in the PLGA conduit filled with r-ADSCs without fibrin matrix group, positive effects were obtained as compared to other implanted groups by increasing the sciatic functional index significantly (p < 0.05). In addition, the diameter nerve fibers had a significant difference mean in the PLGA conduit coated by laminin and conduit filled with r-ADSCs in fibrin matrix groups relative to the autograft group (p < 0.001). However, G-ratio and amplitude (AMP) results showed that fibrin matrix might have beneficial effects on nerve regeneration but, immunohistochemistry and real-time RT-PCR outcomes indicated that the implanted conduit which filled with r-ADSCs, with or without BDNF-CNPs and AuNPs-CNPs had significantly higher expression of S100 and MBP markers than other conduit implanted groups (p < 0.05). CONCLUSIONS: It seems, in this study differential effects of fibrin matrix, could be interfered it with other factors thereby and further studies are required to determine the distinctive effects of fibrin matrix combination with other exogenous factors in peripheral nerve regeneration.

Bone Marrow Aspirate Matrix: A Convenient Ally in Regenerative Medicine.

The rise in musculoskeletal disorders has prompted medical experts to devise novel effective alternatives to treat complicated orthopedic conditions. The ever-expanding field of regenerative medicine has allowed researchers to appreciate the therapeutic value of bone marrow-derived biological products, such as the bone marrow aspirate (BMA) clot, a potent orthobiologic which has often been dismissed and regarded as a technical complication. Numerous in vitro and in vivo studies have contributed to the expansion of medical knowledge, revealing optimistic results concerning the application of autologous bone marrow towards various impactful disorders. The bone marrow accommodates a diverse family of cell populations and a rich secretome; therefore, autologous BMA-derived products such as the "BMA Matrix", may represent a safe and viable approach, able to reduce the costs and some drawbacks linked to the expansion of bone marrow. BMA provides -it eliminates many hurdles associated with its preparation, especially in regards to regulatory compliance. The BMA Matrix represents a suitable alternative, indicated for the enhancement of tissue repair mechanisms by modulating inflammation and acting as a natural biological scaffold as well as a reservoir of cytokines and growth factors that support cell activity. Although promising, more clinical studies are warranted in order to further clarify the efficacy of this strategy.

Single-center, consecutive series study of the use of a novel platelet-rich fibrin matrix (PRFM) and beta-tricalcium phosphate in posterolateral lumbar fusion.

PURPOSE: To evaluate the radiographic and clinical outcomes of the combination of platelet-rich fibrin matrix (PRFM) with beta-tricalcium phosphate (ß-TCP) and bone marrow aspirate (BMA) as a graft alternative in posterolateral lumbar fusion procedures. METHODS: Researchers evaluated 50 consecutive patients undergoing one-level to three-level posterolateral lumbar fusion procedures, resulting in a total of 66 operated levels. The primary outcome was evidence of radiographic fusion at 1-year follow-up, assessed by three independent evaluators using the Lenke scoring system. Secondary outcomes included back and leg VAS scores, incidence of reoperations and complications, return-to-work status, and opioid use. RESULTS: At 1-year follow-up, radiographic fusion was observed in 92.4% (61/66) of operated levels. There was significant improvement in VAS scores for both back and leg pain (p < 0.05). Compared to baseline figures, the number of patients using opioid analgesics at 12-months decreased by 38%. The majority (31/50) of patients were retired, yet 68% of employed patients (n = 19) were able to return to work. No surgical site infections were noted, and no revision surgery at the operated level was required. CONCLUSIONS: This is the first report to analyze the combination of PRFM with ß-TCP and BMA for PLF procedures. Our results indicate a rate of fusion similar to those reported using iliac crest bone graft (ICBG), while avoiding donor site morbidity related to ICBG harvesting such as hematoma, pain, and infection. These slides can be retrieved under Electronic Supplementary Material.

Disc cell therapy with bone-marrow-derived autologous mesenchymal stromal cells in a large porcine disc degeneration model.

PURPOSE: Disc regeneration through matrix-assisted autologous mesenchymal stromal cell therapy seems promising against disc degeneration with convincing results in small animal models. Whether these positive results can be transferred to larger animal models or humans is unclear. METHODS: Fibrin matrix-assisted autologous bone-marrow-derived mesenchymal stromal cell therapy was compared to acellular fibrin matrix therapy in a porcine in vivo model. First, disc degeneration was induced by annular puncture and partial nucleotomy with a large 16G-needle, and 12 weeks later, disc therapy was performed in a second surgery with a thinner 26G needle. Seventy-two lumbar discs from 12 aged adult pigs were evaluated by histology, micro-CT, and gene expression analysis 13 and 24 weeks after nucleotomy and 1 and 12 weeks after treatment, respectively. RESULTS: Radiologic disc height was not significantly different in both treatment groups. In the semi-quantitative histologic degeneration score, significant disc degeneration was still evident 1 week after treatment both in the mesenchymal stromal cell group and in the acellular fibrin matrix group. 12 weeks after treatment, degeneration was, however, not further increased and mesenchymal-stromal-cell-treated discs showed significantly less disc degeneration in the annulus fibrosus (p = 0.02), whereas reduction in the nucleus pulposus did not reach statistical significance. Cell treatment compared to matrix alone found less Col1 gene expression as a marker for fibrosis and more expression of the trophic factor BMP2 in the nucleus pulposus, whereas the inflammation marker IL1ß was reduced in the annulus fibrosus. CONCLUSIONS: Disc treatment with fibrin matrix-assisted autologous mesenchymal stromal cells reduced degenerative findings compared to acellular fibrin matrix alone. Regenerative changes, however, were not significant for all parameters showing limitations in a large biomechanically demanding model with aged discs. These slides can be retrieved under Electronic Supplementary Material.

A novel fibrin-based artificial ovary prototype resembling human ovarian tissue in terms of architecture and rigidity.

PURPOSE: The aim of this study is to optimize fibrin matrix composition in order to mimic human ovarian tissue architecture for human ovarian follicle encapsulation and grafting. METHODS: Ultrastructure of fresh human ovarian cortex in age-related women (n = 3) and different fibrin formulations (F12.5/T1, F30/T50, F50/T50, F75/T75), rheology of fibrin matrices and histology of isolated and encapsulated human ovarian follicles in these matrices. RESULTS: Fresh human ovarian cortex showed a highly fibrous and structurally inhomogeneous architecture in three age-related patients, but the mean ± SD of fiber thickness (61.3 to 72.4 nm) was comparable between patients. When the fiber thickness of four different fibrin formulations was compared with human ovarian cortex, F50/T50 and F75/T75 showed similar fiber diameters to native tissue, while F12.5/T1 was significantly different (p value < 0.01). In addition, increased concentrations of fibrin exhibited enhanced storage modulus with F50/T50, resembling physiological ovarian rigidity. Excluding F12.5/T1 from further analysis, only three remaining fibrin matrices (F30/T50, F50/T50, F75/T75) were histologically investigated. For this, frozen-thawed fragments of human ovarian tissue collected from 22 patients were used to isolate ovarian follicles and encapsulate them in the three fibrin formulations. All three yielded similar follicle recovery and loss rates soon after encapsulation. Therefore, based on fiber thickness, porosity, and rigidity, we selected F50/T50 as the fibrin formulation that best mimics native tissue. CONCLUSIONS: Of all the different fibrin matrix concentrations tested, F50/T50 emerged as the combination of choice in terms of ultrastructure and rigidity, most closely resembling human ovarian cortex.

Further insights into the impact of mouse follicle stage on graft outcome in an artificial ovary environment.

STUDY QUESTION: Are mouse preantral follicles differently affected by isolation, encapsulation and/or grafting procedures according to stage? SUMMARY ANSWER: Isolated secondary follicles showed superior ability to survive and grow after transplantation, which was not related to a particular effect of the isolation and/or grafting procedure, but rather to their own ability to induce neoangiogenesis. WHAT IS KNOWN ALREADY: Isolated and encapsulated mouse preantral follicles can survive (6-27%) and grow (80-100%) in a fibrin matrix with a low concentration of fibrinogen and thrombin (F12.5/T1) after short-term transplantation. STUDY DESIGN, SIZE, DURATION: An in vivo experimental model using 20 donor Naval Medical Research Institute (NMRI) mice (6-25 weeks of age) and 14 recipient severe combined immunodeficient (SCID) mice (11-39 weeks of age) was applied. Each NMRI mouse underwent mechanical disruption of both ovaries and isolation of primordial-primary and secondary follicles with ovarian stromal cells, in order to encapsulate them in an F12.5/T1 matrix. Twelve out of 40 fibrin clots were immediately fixed as controls (D0) (10 for histology and 2 for scanning electron microscopy [SEM]) and the others (n = 28) were grafted to the inner part of the peritoneum for 2 (16 fibrin clots) or 7 (12 fibrin clots) days (D2 and D7). PARTICIPANTS/MATERIALS, SETTING, METHODS: This study involved the participation of the Gynecology Research Unit (Universitè Catholique de Louvain) and the Physiological Sciences Department (University of Brasília). Specific techniques were used to analyze the follicle recovery rate (hematoxylin-eosin staining), vascularization (CD34) and follicle ultrastructure (transmission electron microscopy [TEM] and SEM). MAIN RESULTS AND THE ROLE OF CHANCE: After follicle isolation and encapsulation, a statistically higher percentage of normal follicles was observed in the secondary group (62%) than in the primordial-primary group (47%). Follicle recovery rates were 34% and 62% for primordial-primary and secondary follicles on D2, respectively, and 12% and 42% on D7, confirming that secondary follicles survive better than primordial-primary follicles after grafting. Concerning vascularization, both follicle stages exhibited similar vascularization to that seen in control mouse ovary on D7, but a significantly higher number of vessels and greater vessel surface area were detected in the secondary follicle group. Despite structural differences in fiber density between fibrin clots and ovarian tissue observed by SEM and TEM, preantral follicles appeared to be well encapsulated in the matrix, also showing a normal ultrastructure after grafting. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: As demonstrated by our results during the isolation procedure, we encapsulated a significantly higher number of round structures in the primordial-primary group than in the secondary group, which could partially explain the lower recovery rate of early-stage follicles in our previous study. However, it is not excluded that the physical and mechanical properties of the fibrin matrix may also play a role in follicle survival and growth, so further investigations are needed. WIDER IMPLICATIONS OF THE FINDINGS: This research represents one more key step in the creation of the artificial ovary. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS) to C.A. Amorim as a research associate at FRS-FNRS and (grant 5/4/150/5 awarded to M.M. Dolmans), Fonds Spéciaux de Recherche, Fondation St Luc, Foundation Against Cancer, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-Brazil) (grant #013/14 CAPES/WBI awarded to C.M. Lucci, with F. Paulini receiving a post-doctoral fellowship), and Wallonie-Bruxelles International, and donations from the Ferrero family. None of the authors have any competing interests to declare in relation to the topic.

Influence of follicle stage on artificial ovary outcome using fibrin as a matrix.

STUDY QUESTION: Do primordial-primary versus secondary follicles embedded inside a fibrin matrix have different capabilities to survive and grow after isolation and transplantation? SUMMARY ANSWER: Mouse primordial-primary follicles showed a lower recovery rate than secondary follicles, but both were able to grow. WHAT IS KNOWN ALREADY: Fresh isolated mouse follicles and ovarian stromal cells embedded in a fibrin matrix are capable of surviving and developing after short-term autografting. STUDY DESIGN, SIZE, DURATION: In vivo experimental model using 11 donor Naval Medical Research Institute (NMRI) mice and 11 recipient severe combined immunodeficiency (SCID) mice. Both ovaries from all NMRI mice were mechanically disrupted and primordial-primary and secondary follicles were isolated with ovarian stromal cells. They were then encapsulated in a fibrin matrix composed of 12.5 mg/ml of fibrinogen (F12.5) and 1 IU/ml of thrombin (T1) (F12.5/T1), and grafted to the inner part of the peritoneum of SCID mice for 2 and 7 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was conducted at the Gynecology Research Unit, Université Catholique de Louvain. All materials were used to conduct histological (H-E staining) and immunohistochemical (Ki67, TUNEL) analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Although all grafted fibrin clots were recovered, the follicle recovery rate on day 2 was 16 and 40% for primordial-primary and secondary follicles respectively, while on day 7, it was 6 and 28%. The secondary group showed a significantly higher recovery rate than the primordial-primary group (23%, P-value <0.001). Follicles found in both groups were viable, as demonstrated by live/dead assays, and no difference was observed in the apoptosis rate between groups, as evidenced by TUNEL. Their growth to further stages was confirmed by Ki67 immunostaining. LIMITATIONS, REASONS FOR CAUTION: As demonstrated by our results, secondary follicles appear to be more likely to survive and develop than primordial-primary follicles in a fibrin matrix after both periods of grafting. These findings may also be attributed to the specific features of the fibrin matrix, which could benefit larger follicles, but not smaller follicles. WIDER IMPLICATIONS OF THE FINDINGS: This study is essential to understanding possible impairment caused by factors such as the isolation procedure or fibrin matrix composition to the survival and development of different follicle stages. It therefore provides the basis for further investigations with longer periods of grafting. STUDY FUNDING/COMPETING INTERESTS: This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (grant Télévie No. 7.4578.14 and 7.4627.13, grant 5/4/150/5 awarded to Marie-Madeleine Dolmans), Fonds Spéciaux de Recherche, Fondation St Luc, the Foundation Against Cancer, and the Region Wallone (Convention N°6519-OVART) and donations from Mr Pietro Ferrero, Baron Frère and Viscount Philippe de Spoelberch. None of the authors have any competing interests to declare.

Survival and growth of human preantral follicles after cryopreservation of ovarian tissue, follicle isolation and short-term xenografting.

In women, chemotherapy and radiotherapy can be harmful to the ovaries, causing loss of endocrine and reproductive functions. When gonadotoxic treatment cannot be delayed, ovarian tissue cryobanking is the only way of preserving fertility. This technique, however, is not advisable for patients with certain types of cancer, because of the risk of reintroducing malignant cells present in the cryopreserved tissue. Our objective is therefore to develop a transplantable artificial ovary. To this end, cryopreserved human preantral follicles were isolated and embedded in fibrin formulations prepared with 50 mg/ml fibrinogen and 10 IU/ml thrombin supplemented or not with 3% hyaluronic acid, and respectively xenografted to specially created right and left peritoneal pockets in eight nude mice. On days 0 and 7, the animals were killed and the matrices retrieved. On day 7, no difference was observed in the recovery rate of follicles embedded in fibrin alone (23.4%) or fibrin-hyaluronic acid (20.5%). Ki67 staining confirmed growth of the grafted follicles and terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling assay revealed 100% of the follicles to be viable in both groups on day 7. In conclusion, fibrin seems to be a promising material for creation of an artificial ovary, supporting follicle survival and development.

Use of Platelet Preparations in Facial Rejuvenation and Wound Healing Remains Unproven.

UNLABELLED: There is growing interest in the use of platelet derivatives in facial aesthetic surgery and wound healing. Sclafani et al. have concluded from their review of the literature that the vast majority of studies show a significant and measurable effect on facial aesthetic outcomes with the use of these platelet preparations. We suggest that an alternative review of the same literature may well have produced a different set of conclusions. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Fibronectin alters the rate of formation and structure of the fibrin matrix.

Plasma fibronectin is a vital component of the fibrin clot; however its role on clot structure is not clearly understood. The goal of this study was to examine the influence of fibronectin on the kinetics of formation, structural characteristics and composition of reconstituted fibrin clots or fibrin matrices. Fibrin matrices were formed by adding thrombin to 1, 2 or 4 mg/ml fibrinogen supplemented with 0-0.4 mg/ml fibronectin. The rate of fibrin matrix formation was then monitored by measuring light absorbance properties at different time points. Confocal microscopy of fluorescein conjugated fibrinogen was used to visualize the structural characteristics of fibrin matrices. The amount of fibronectin in fibrin matrices was determined through electrophoresis and immunoblotting of solubilized matrices. Fibronectin concentration positively correlated with the initial rate of fibrin matrix formation and with steady state light absorbance values of fibrin matrices. An increase in fibronectin concentration resulted in thinner and denser fibers in the fibrin matrices. Electrophoresis and immunoblotting showed that fibronectin was covalently and non-covalently bound to fibrin matrices and in the form of high molecular weight multimers. The formation of fibronectin multimers was attributed to cross-linking of fibronectin by trace amounts Factor XIIIa. These findings are novel because they link results from light absorbance studies to microcopy analyses and demonstrate an influence of fibronectin on fibrin matrix structural characteristics. This data is important in developing therapies that destabilize fibrin clots.

Fabrication of Artificial Nerve Conduits Used in a Long Nerve Gap: Current Reviews and Future Studies.

There are many commercially available artificial nerve conduits, used mostly to repair short gaps in sensory nerves. The stages of nerve regeneration in a nerve conduit are fibrin matrix formation between the nerve stumps joined to the conduit, capillary extension and Schwann cell migration from both nerve stumps, and, finally, axon extension from the proximal nerve stump. Artificial nerves connecting transected nerve stumps with a long interstump gap should be biodegradable, soft and pliable; have the ability to maintain an intrachamber fibrin matrix structure that allows capillary invasion of the tubular lumen, inhibition of scar tissue invasion and leakage of intratubular neurochemical factors from the chamber; and be able to accommodate cells that produce neurochemical factors that promote nerve regeneration. Here, we describe current progress in the development of artificial nerve conduits and the future studies needed to create nerve conduits, the nerve regeneration of which is compatible with that of an autologous nerve graft transplanted over a long nerve gap.

Surgical and Biological Treatment with a Platelet-Rich Fibrin Matrix for Patellar Tendinopathy: Clinical Outcomes and Return to Sport at 2-Year Follow-Up.

BACKGROUND: Patellar tendinopathy (PT) involves anterior knee pain and functional. Platelet-rich fibrin matrix (PRFM) is a promising biological therapy for tendinopathies. We examined a cohort of PT patients treated with tendon debridement and autologous PRFM at the 24-month follow-up to assess whether the combined treatment facilitated return to sports and yielded satisfactory clinical and functional scores. METHODS: Baseline and 24-month visual analogue scale (VAS), Victorian Institute of Sport Assessment Scale for Patellar Tendinopathy (VISA-P), Tegner Activity Scale (TAS), and Blazina scores were compared to evaluate treatment effectiveness. The Friedman test was used to compare repeated observations of VAS, VISA-P, TAS, and Blazina Score values. Return to sport rate, Tampa Scale of Kinesiophobia (TKS) score and patient satisfaction were collected at 24 months. RESULTS: The postoperative clinical scores demonstrated significant improvement compared with their preoperative values (all p < 0.001). Specifically, the VISA-P score was 80.32 (±20.58), 92.10% of patients had resumed sports activities and patient satisfaction was 9.21 (±1.21) at 24 months. CONCLUSIONS: Surgical debridement and autologous PRFM application in patients with chronic PT resulted in a higher rate of return to sports when compared to solely surgical treatment, significantly improved clinical outcomes and excellent patient satisfaction at 24 months.

Evaluation of platelet-rich fibrin matrix combined with PGE-1 injection on erectile function in patients with refractory response to PDE5-I: a randomized placebo-controlled study.

PURPOSE: We studied the effect of a platelet-rich fibrin matrix (PRFM) combined with prostaglandin E-1 (PGE-1) injection on erectile function in patients refractory to response for phosphodiesterase type 5 inhibitors (PDE5-Is). METHODS: This randomized, double-blind, placebo-controlled study included 80 patients. The patients were randomly assigned to four groups and blinded together with the administrating physicians to the nature of the intracorporeal injection (ICI) therapies. Group (1) received saline, group (2) received platelet-rich fibrin matrix (PRFM), group (3) received prostaglandin E-1 (PGE-1), and group (4) received a combination of PRFM + PGE-1. The patients received ICI therapy weekly for 8 consecutive weeks. Clinical information and follow-up data were obtained at 1, 2, 3, and 6 months. RESULTS: A significant increase occurred in the validated Arabic version of the International Index of Erectile Function (ArIIEF-5) score in group (4) compared to the other three groups (p value = 0.037). There was a significant difference in erection hardness scale (EHS) scores among all groups after receiving the different treatments (p = 0.004). A significant increase was seen in the ArIIEF-5 score in groups 4 and 3 compared to that in groups 1 and 2 (p < 0.001). There was also a significant increase in the arterial dilatation % in groups 4 and 3 compared to that in groups 1 and 2 (p = 0.019). CONCLUSION: The combination of PRFM plus PGE-1 had shown significant improvement in the ArIIEF-5 score, yet the patients still had mild to moderate ED.

In vivo neural tissue engineering using adipose-derived mesenchymal stem cells and fibrin matrix.

BACKGROUND: The multipotency of adipose-derived mesenchymal stem cells (ADMSC) could be an advantage to regenerate tissues with multiple cell types. However, due to the hostile nature, trauma sites like spinal cord injury can augment the ADMSC differentiation into undesirable lineages. Immersing pre-differentiated neural progenitors in a biomimetic niche during delivery could guard them against any undesired differentiation or death. OBJECTIVE: The study proposes using an insoluble cell-specific fibrin niche for in vitro differentiation of rat ADMSCs to neural progenitor cells (NPCs) and oligodendrocyte progenitor cells (OPCs). Further, the study explores fibrin hydrogel for in vivo progenitor cell delivery, and that can aid post-transplant survival/differentiation. DESIGN: The in vitro experiments analyzed for differentiation-specific markers to establish derivation of rADMSCs to rNPCs and rOPCs. The derived progenitors, tagged with fluorescent tracker dye were delivered in rat T10 contusion SCI using fibrin hydrogel. After 28 days, imaged the experiment site to determine cell survival, immunostained the tissues to identify differentiation of transplanted cells, and evaluated the effect of fibrin and cells on regulating the injury-associated immune response. RESULTS: The study demonstrated fibrin niche aided stable differentiation of rat ADMSCs into neural progenitors. Fibrin matrix holds up the delivered progenitor cells in the SCI site. The H&E stained tissues revealed regulated cavitation, astrogliosis, and inflammation in test tissues. Progression of transplanted cells into oligodendrocytes upon delivering a mixture of rNPCs, rOPCs, and fibrin is evident. CONCLUSION: Fibrin niche-based derivation of neural progenitors from ADMSC seems valuable for transplantation using fibrin hydrogel. It is a promising strategy for extensive study towards further development of translational stem cell-based neural replacement therapy.

A Comparative Study on Therapeutic Efficacy of Autologous Platelet-rich Plasma, Autologous Platelet-rich Fibrin Matrix, Recombinant Human Epidermal Growth Factor, and Collagen Particles in Nonhealing Leg Ulcers.

Background: Nonhealing leg ulcers are challenging to manage and cause significant patient morbidity. To promote healing, newer techniques focus on delivering/enhancing dermal matrix components. Aim: The aim of this study was to compare the therapeutic efficacy of autologous platelet-rich plasma (PRP), autologous platelet-rich fibrin matrix (PRFM), recombinant human epidermal growth factor (rhEGF), and collagen particles in treating nonhealing leg ulcers. Materials and Methods: Open, randomized prospective study was conducted in a single tertiary center over 2 years where after fulfilling the criteria, randomization was done into four groups. Group A: Autologous PRP (double spin, manual method, weekly); Group B: Autologous PRFM (weekly); Group C: rhEGF (daily application); and Group D: Collagen particles (weekly) along with cleansing, debris removal, and wound dressing. Treatment endpoints were complete healing/6 months of treatment, whichever was earlier. Follow-up was done two weekly by clinical assessment, photographs, and measurement of the ulcer area. Epi info 7 software was used for statistical analysis. Results: A total of 48 patients completed the study, 12 in each group, with mean age: 42.37 ± 4.56 years and male-to-female ratio 2.6:1. Underlying etiology was varicosities (43.75%), traumatic (25%), diabetes (22.91%), and leprosy (8.34%). At baseline, all groups were comparable in terms of patient and ulcer characteristics. Complete healing was seen in 79.17% at the end of 12 weeks: 91.67% of patients from Groups A and B each, and 66.67% from Groups C and D each. The mean time to complete healing was 6.9 ± 2.5 weeks, the least in Group B (4.73 ± 2.3 weeks). Differences between excellent (≥75%) ulcer healing across all groups were statistically significant at the end of 8 weeks where Group B showed maximum improvement. No major adverse events were seen. Conclusion: PRFM resulted in relatively faster ulcer healing compared with other modalities.

Endothelial Cell Fibrin Gel Angiogenesis Bead Assay.

The fibrin gel angiogenesis bead assay provides a controlled in vitro setting for observing endothelial angiogenic sprouting in response to modified variables. Endothelial cells are coated onto microcarriers and embedded into a fibrin clot containing necessary growth factors. Following a 24-h incubation, endothelial sprouts are imaged using a light microscope. This method is useful for rapidly and affordably investigating the effects of genetic or chemical manipulation to endothelial function.

Advantages of Fibrin Polymerization Method without the Use of Exogenous Thrombin for Vascular Tissue Engineering Applications.

Fibrin is widely used in vascular tissue engineering. Typically, fibrin polymerization is initiated by adding exogenous thrombin. In this study, we proposed a protocol for the preparation of completely autologous fibrin without the use of endogenous thrombin and compared the properties of the prepared fibrin matrix with that obtained by the traditional method. Fibrinogen was obtained by ethanol precipitation followed by fibrin polymerization by adding either exogenous thrombin and calcium chloride (ExThr), or only calcium chloride (EnThr). We examined the structure, mechanical properties, thrombogenicity, degradation rate and cytocompatibility of fibrin matrices. Factor XIII (FXIII) quantitative assay was performed by ELISA, and FXIII activity was assessed by SDS-PAGE detection of γ-γ cross-links. The results show that network structure of EnThr fibrin was characterized by thinner fibers. The EnThr fibrin matrices had higher strength, stiffness and resistance to proteolytic degradation compared to ExThr fibrin. EnThr fibrin matrices exhibited less thrombogenicity in vitro than ExThr, and retained high cytocompatibility. Thus, the proposed approach has several advantages over the traditional method, namely the fabrication of a completely autologous coating material that has better mechanical properties, higher resistance to proteolysis and lower thrombogenicity.

Platelet-rich plasma use in meniscus repair treatment: a systematic review and meta-analysis of clinical studies.

BACKGROUND: There is conflicting clinical evidence whether platelet-rich plasma (PRP) therapies could translate to an increased meniscus healing rate and improved functional outcomes. The objective of this systematic review and meta-analysis was to compare the failure rate and patient-reported functional outcomes in meniscus repair augmented with and without PRP. METHODS: We comprehensively searched the PubMed, Web of Science, Medline, Embase, and Cochrane Library databases to identify studies that compared the clinical efficacy of meniscus repair performed with PRP versus without PRP. The primary outcome was the meniscus repair failure rate, while the secondary outcomes were knee-specific patient-reported outcomes, including the International Knee Documentation Committee (IKDC) score, Lysholm knee scale, visual analog scale, Tegner activity level score, Western Ontario and McMaster Universities Osteoarthritis Index score, Single Assessment Numeric Evaluation score, and Knee injury and Osteoarthritis Outcome Score. Furthermore, subgroup analyses were performed by stratifying the studies according to the PRP preparation technique to investigate the potential sources of heterogeneity among studies. RESULTS: Our meta-analysis included nine studies (two RCTs and seven non-RCTs) with 1164 participants. The failure rate in the PRP group was significantly lower than that in the non-PRP group [odds ratio: 0.64, 95% confidence interval (CI) (0.42, 0.96), P = 0.03]. Furthermore, the PRP group was associated with a statistically significant improvement in the visual analog scale for pain [Mean difference (MD): - 0.76, 95% CI (- 1.32, - 0.21), P = 0.007] and Knee injury and Osteoarthritis Outcome Score-symptom [MD: 8.02, 95% CI (2.99, 13.05), P = 0.002] compared with the non-PRP group. However, neither the IKDC score nor the Lysholm knee scale showed any differences between the two groups. In addition, the results of subgroup analyses favored PRP over platelet-rich fibrin matrix (PRFM) regarding the IKDC score. CONCLUSIONS: Although meniscus repairs augmented with PRP led to significantly lower failure rates and better postoperative pain control compared with those of the non-PRP group, there is insufficient RCT evidence to support PRP augmentation of meniscus repair improving functional outcomes. Moreover, PRP could be recommended in meniscus repair augmentation compared with PRFM. PRFM was shown to have no benefit in improving functional outcomes.