Engineered PDGFA-ligand-modified exosomes delivery T3 for demyelinating disease targeted therapy.

Demyelination is a proper syndrome in plenty of central nervous system (CNS) diseases, which is the main obstacle to recovery and still lacks an effective treatment. To overcome the limitations of the brain-blood barrier on drug permeability, we modified an exosome secreted by neural stem cells (NSCs), which had transfected with lentivirus armed with platelet-derived growth factors A (PDGFA)-ligand. Through the in vivo and in vitro exosomes targeting test, the migration ability to the lesion areas and OPCs significantly improved after ligand modification. Furthermore, the targeted exosomes loaded with 3,5, 30-L-triiodothyronine (T3) have a critical myelination ability in CNS development, administrated to the cuprizone animal model treatment. The data shows that the novel drug vector loaded with T3 significantly promotes remyelination compared with T3 alone. At the same time, it improved the CNS microenvironment by reducing astrogliosis, inhibiting pro-inflammatory microglia, and alleviating axon damage. This investigation provides a straightforward strategy to produce a targeting exosome and indicates a possible therapeutic manner for demyelinating disease.

PDGF Receptors and Signaling Are Required for 3D-Structure Formation and Differentiation of Human iPSC-Derived Hepatic Spheroids.

Human iPSC-derived liver organoids (LO) or hepatic spheroids (HS) have attracted widespread interest, and the numerous studies on them have recently provided various production protocols. However, the mechanism by which the 3D structures of LO and HS are formed from the 2D-cultured cells and the mechanism of the LO and HS maturation remain largely unknown. In this study, we demonstrate that PDGFRA is specifically induced in the cells that are suitable for HS formation and that PDGF receptors and signaling are required for HS formation and maturation. Additionally, in vivo, we show that the localization of PDGFRα is in complete agreement with mouse E9.5 hepatoblasts, which begin to form the 3D-structural liver bud from the single layer. Our results present that PDGFRA play important roles for 3D structure formation and maturation of hepatocytes in vitro and in vivo and provide a clue to elucidate the hepatocyte differentiation mechanism.

Role of PDGF-A/B Ligands in Cardiac Repair After Myocardial Infarction.

Platelet-derived growth factors (PDGFs) are powerful inducers of cellular mitosis, migration, angiogenesis, and matrix modulation that play pivotal roles in the development, homeostasis, and healing of cardiac tissues. PDGFs are key signaling molecules and important drug targets in the treatment of cardiovascular disease as multiple researchers have shown that delivery of recombinant PDGF ligands during or after myocardial infarction can reduce mortality and improve cardiac function in both rodents and porcine models. The mechanism involved cannot be easily elucidated due to the complexity of PDGF regulatory activities, crosstalk with other protein tyrosine kinase activators, and diversity of the pathological milieu. This review outlines the possible roles of PDGF ligands A and B in the healing of cardiac tissues including reduced cell death, improved vascularization, and improved extracellular matrix remodeling to improve cardiac architecture and function after acute myocardial injury. This review may highlight the use of recombinant PDGF-A and PDGF-B as a potential therapeutic modality in the treatment of cardiac injury.

Self-assembly of differentiated progenitor cells facilitates spheroid human skin organoid formation and planar skin regeneration.

Self-assembly of solid organs from single cells would greatly expand applicability of regenerative medicine. Stem/progenitor cells can self-organize into micro-sized organ units, termed organoids, partially modelling tissue function and regeneration. Here we demonstrated 3D self-assembly of adult and induced pluripotent stem cell (iPSC)-derived fibroblasts, keratinocytes and endothelial progenitors into both, planar human skin in vivo and a novel type of spheroid-shaped skin organoids in vitro, under the aegis of human platelet lysate. Methods: Primary endothelial colony forming cells (ECFCs), skin fibroblasts (FBs) and keratinocytes (KCs) were isolated from human tissues and polyclonally propagated under 2D xeno-free conditions. Human tissue-derived iPSCs were differentiated into endothelial cells (hiPSC-ECs), fibroblasts (hiPSC-FBs) and keratinocytes (hiPSC-KCs) according to efficiency-optimized protocols. Cell identity and purity were confirmed by flow cytometry and clonogenicity indicated their stem/progenitor potential. Triple cell type floating spheroids formation was promoted by human platelet-derived growth factors containing culture conditions, using nanoparticle cell labelling for monitoring the organization process. Planar human skin regeneration was assessed in full-thickness wounds of immune-deficient mice upon transplantation of hiPSC-derived single cell suspensions. Results: Organoids displayed a distinct architecture with surface-anchored keratinocytes surrounding a stromal core, and specific signaling patterns in response to inflammatory stimuli. FGF-7 mRNA transfection was required to accelerate keratinocyte long-term fitness. Stratified human skin also self-assembled within two weeks after either adult- or iPSC-derived skin cell-suspension liquid-transplantation, healing deep wounds of mice. Transplant vascularization significantly accelerated in the presence of co-transplanted endothelial progenitors. Mechanistically, extracellular vesicles mediated the multifactorial platelet-derived trophic effects. No tumorigenesis occurred upon xenografting. Conclusion: This illustrates the superordinate progenitor self-organization principle and permits novel rapid 3D skin-related pharmaceutical high-content testing opportunities with floating spheroid skin organoids. Multi-cell transplant self-organization facilitates development of iPSC-based organ regeneration strategies using cell suspension transplantation supported by human platelet factors.

An Injectable Multifunctional Dual-Phase Bead-Reinforced Gelatin Matrix Permissive of Mesenchymal Stem Cell Infiltration for Musculoskeletal Soft Tissue Repair.

This study develops a novel strategy for regenerative therapy of musculoskeletal soft tissue defects using a dual-phase multifunctional injectable gelatin-hydroxyphenyl propionic acid (Gtn-HPA) composite. The dual-phase gel consists of stiff, degradation-resistant, ≈2-mm diameter spherical beads made from 8 wt% Gtn-HPA in a 2 wt% Gtn-HPA matrix. The results of a 3D migration assay show that both the cell number and migration distance in the dual-phase gel system are comparable with the 2 wt% mono-phase Gtn-HPA, but notably significantly higher than for 8 wt% mono-phase Gtn-HPA (into which few cells migrated). The results also show that the dual phase gel system has degradation resistance and a prolonged growth factor release profile comparable with 8 wt% mono-phase Gtn-HPA. In addition, the compressive modulus of the 2 wt% dual-phase gel system incorporating the 8 wt% bead phase is nearly four-fold higher than the 2 wt% mono-phase gel (5.3 ± 0.4 kPa versus 1.5 ± 0.06 kPa). This novel injectable dual-phase Gtn-HPA composite thus combines the advantages of low-concentration Gtn-HPA (cell migration) with high-concentration Gtn-HPA (stiffness, degradation resistance, slower chemical release kinetics) to facilitate effective reparative/regenerative processes in musculoskeletal soft tissue.

Natural, Synthetic and their Combinatorial Nanocarriers Based Drug Delivery System in the Treatment Paradigm for Wound Healing Via Dermal Targeting.

A wound refers to the epithelial loss, accompanied by loss of muscle fibers collagen, nerves and bone instigated by surgery, trauma, frictions or by heat. Process of wound healing is a compounded activity of recovering the functional integrity of the damaged tissues. This process is mediated by various cytokines and growth factors usually liberated at the wound site. A plethora of herbal and synthetic drugs, as well as photodynamic therapy, is available to facilitate the process of wound healing. Generally, the systems used for the management of wounds tend to act through covering the ruptured site, reduce pain, inflammation, and prevent the invasion and growth of microorganisms. The available systems are, though, enough to meet these requirements, but the involvement of nanotechnology can ameliorate the performance of these protective coverings. In recent years, nano-based formulations have gained immense popularity among researchers for the wound healing process due to the enhanced benefits they offer over the conventional preparations. Hereupon, this review aims to cover the entire roadmap of wound healing, beginning from the molecular factors involved in the process, the various synthetic and herbal agents, and combination therapy available for the treatment and the current nano-based systems available for delivery through the topical route for wound healing.

Platelet Adhesion on Commercially Pure Titanium Plates in Vitro II. Immunofluorescence Visualization of PDGF-B, TGFß1, and PPARγ Released from Activated Adherent Platelets.

Recent progress in the industrial development of dental implants has improved their surface bio-affinity, while clinical implantologists attempt to improve it through coating with various compounds, including platelet-rich plasma (PRP) in clinical settings. However, it is poorly understood how PRP acts on titanium surfaces. To validate this surface modification method and demonstrate how platelet-derived soluble biomolecules released from the activated adherent platelets act on plain, commercially pure-titanium (cp-Ti) plates, we evaluated the distribution of biomolecules by immunofluorescence. PPARγ, PDGF-B, and TGFß1 were similarly released at immunofluorescence levels from activated adherent platelets, retained in the surrounding extra-platelet spaces for a while, and did not immediately diffuse away to distant spaces. Exogenously added CaCl2 augmented release and retention of those biomolecules along with activation and aggregation. Taken together with our previous data regarding platelet adhesion, these findings suggest that especially when treated with CaCl2, platelets immediately adhere on cp-Ti plates to release their stored biomolecules in the absence of plasma proteins and that these biomolecules do not diffuse away, but stay longer in extra-platelet spaces around the platelets by newly formed, immature fibrin fiber fragments. Consequently, these retained biomolecules are anticipated to cooperatively stabilize implants by stimulating alveolar bone regeneration and integration.

Platelet-Rich Plasma and Platelet-Rich Fibrin in Periodontal Regeneration: A Review.

Platelet concentrates (PCs; platelet-rich plasma and platelet-rich fibrin) are autologous bioactive substances that have found varied application in medical and dental fields, particularly in oral and maxillofacial surgery, plastic surgery, and sports medicine. The rationale of these technologies is to extract all the elements from patient's own blood sample, which could be used to improve healing by promoting tissue regeneration. PCs have evolved a long way since its introduction in 1954. PCs have been used successfully in periodontics and implant dentistry. However, the preparation protocol, processing time, transfer of concentrates, centrifugation temperature, vibration, etc., being not standardized are various factors for the mixed results reported in the literature. This review intends to discuss evolution of PCs, their preparation techniques, and their clinical and technical aspects and applications.

Heparin-Conjugated Decellularized Bone Particles Promote Enhanced Osteogenic Signaling of PDGF-BB to Adipose-Derived Stem Cells in Tissue Engineered Bone Grafts.

Adipose-derived stem cells (ASCs) are a promising cell source for regenerating critical-sized craniofacial bone defects, but their clinical use is limited due to the supraphysiological levels of bone morphogenetic protein-2 required to induce bone formation in large grafts. It has been recently reported that platelet-derived growth factor-BB (PDGF) directly enhances the osteogenesis of ASCs when applied at physiological concentrations. In this study, a biomimetic delivery system that tethers PDGF to decellularized bone matrix (DCB) is developed to enhance osteogenic signaling in bone grafts by colocalizing PDGF-extracellular matrix cues. Heparin is conjugated to DCB particles (HC-DCB) to promote sustained binding of PDGF via electrostatic interactions. HC-DCB particles bind to PDGF with >99% efficiency and release significantly less PDGF over 21 days compared to nonconjugated DCB particles (1.1% vs 22.8%). HC-DCB-PDGF signaling in polycaprolactone (PCL)-fibrin grafts promotes >40 µg Ca2+ µg-1 DNA deposition by ASCs during in vitro osteogenic culture compared to grafts without HC-DCB or PDGF. Furthermore, more bone formation is observed in grafts with HC-DCB-PDGF at 12 weeks following implantation of grafts into murine critical-sized calvarial defects. Collectively, these results demonstrate that HC-DCB enhances the osteogenic signaling of PDGF to ASCs and may be applied to promote ASC-mediated bone regeneration in critical-sized defects.

Effectiveness of Platelet Rich Plasma and Bone Graft in the Treatment of Intrabony Defects: A Clinico-radiographic Study.

BACKGROUND & OBJECTIVES: Periodontal disease is characterized by the presence of gingival inflammation, periodontal pocket formation, loss of connective tissue attachment and alveolar bone around the affected tooth. Different modalities have been employed in the treatment and regeneration of periodontal defects which include the use of bone grafts, PRP and other growth factors.The purpose of this prospective, randomized controlled study was to compare the regenerative efficacy of PRP and bonegraft in intrabony periodontal defects. METHODOLOGY: This randomized control trial was carried out in the Department of Periodontics & Oral Implantology, Kalinga Institute of Dental Sciences and Hospital, KIIT University, Bhubaneswar. The study sample included 20 periodontal infrabony defects in 20 patients, 12 males and 8 females. The patients were aged between 25 -45 years(with mean age of 35 years). The 20 sites selected for the study were was randomly divided into 2 groups of 10 sites each. Group A: PRP alone, Group B: Bone Graft. STATISTICAL ANAYSIS & RESULTS STATISTICAL ANALYSIS WAS DONE USING SPSS VERSION 180: Statistical analysis was done usingpaired 't' tests and ANOVA that revealed a significant reduction ingingival index, plaque index, probing pocket depth and gain in clinical attachment level at various time intervalswithin both the groups. Radiographic evaluation revealed statistically significant defect fill (p<0.001) at the end of 6months within both the groups. However, there was astatistically significant difference seen in group B radiographically, when compared to group A. CONCLUSION: Both the groups showed promising results in enhancing periodontal regeneration; however the resultswith bonegraftwere comparatively better, although not statistically significant when compared to PRP alone.

Treatment of knee osteoarthritis: platelet-derived growth factors vs. hyaluronic acid. A randomized controlled trial.

OBJECTIVE: Aim of this trial was to compare efficacy of activated platelet-rich plasma against hyaluronic acid as intra-articular injections to people with osteoarthritis of the knee. DESIGN: Phase-2 randomized controlled trial, with blind patients and outcome assessors. SETTING: Outpatient rehabilitation service; years 2011-2013. SUBJECTS: Patients with knee osteoarthritis grades 2-3 at magnetic resonance imaging (MRI) were included after consent and randomized. Target sample size was 25 patients per group. INTERVENTIONS: Patients received three activated platelet-rich plasma (intervention group) or hyaluronic acid (controls) intra-articular injections at 4-week intervals. MAIN MEASURES: Main outcome measure was proportion of patients with >1 grade improvement at six months from last injection, as assessed by a radiologist blind to study group. Patients were evaluated over time clinically and with functional scales (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lysholm, Tegner, American Knee Society Score (AKSS), Lequesne, visual analogue scale (VAS) for pain). RESULTS: Overall, 30 patients were randomized to intervention and 28 to control group. For primary outcome, 28 patients (29 knees) in the intervention and 22 (25 knees) in the control group were available. Patients with at least 1 grade improvement at repeat MRI were 14 (48.3%) in the intervention and 2 (8%) in the control group ( P < 0.003). Improvement in symptoms and functional scales was consistently higher in the intervention group. No side-effects were observed in either group. CONCLUSION: Activated platelet-rich plasma reduces articular damage as evident at MRI, as soon as six months after treatment; it reduces pain and improves patient's function and overall quality of life.

Evolution, current status and advances in application of platelet concentrate in periodontics and implantology.

Platelet concentrates (PC) [platelet-rich plasma (PRP) and platelet-rich fibrin (PRF)] are frequently used for surgical procedures in medical and dental fields, particularly in oral and maxillofacial surgery, plastic surgery and sports medicine. The objective of all these technologies is to extract all the elements from a blood sample that could be used to improve healing and promote tissue regeneration. Although leukocyte rich and leukocyte poor PRP's have their own place in literature, the importance of non-platelet components in a platelet concentrate remains a mystery. PC have come a long way since its first appearance in 1954 to the T-PRF, A-PRF and i-PRF introduced recently. These PC find varied applications successfully in periodontics and implant dentistry as well. However, the technique of preparation, standing time, transfer process, temperature of centrifuge, vibration, etc., are the various factors for the mixed results reported in the literature. Until the introduction of a proper classification of terminologies, the PC were known by different names in different countries and by different commercial companies which also created a lot of confusion. This review intends to clarify all these confusion by briefing the exact evolution of PC, their preparation techniques, recent advances and their various clinical and technical aspects and applications.

Comparison of intra-articular injection of plasma rich in growth factors versus hyaluronic acid following arthroscopy in the treatment of temporomandibular dysfunction: A randomised prospective study.

PURPOSE: The main objective of our study was to evaluate the effectiveness of the injection of plasma rich in platelet-derived growth factors (PRGF) versus hyaluronic acid (HA) following arthroscopic surgery in patients diagnosed with internal derangement of the temporomandibular joint (TMJ) with osteoarthritis (OA). MATERIALS AND METHODS: A total of 100 patients were randomised into two study groups. Group A (n = 50) received an injection of PRGF, and Group B (n = 50) received an injection of HA. The mean age was 35.5 years (range 18-77 years), and 88% of the patients were women. The pain intensity (visual analogue scale) and the extent of maximum mouth opening before and after the procedure were statistically analysed. RESULTS: Better results were observed in the group treated with PRGF, with a significant reduction in pain at 18 months, compared with HA treatment. Regarding mouth opening, an increase was observed in both groups, with no significant difference. CONCLUSIONS: The injection of PRGF following arthroscopy is more effective than the injection of HA with respect to pain in patients with advanced internal derangement of the TMJ.

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

Objective: to compare the platelet concentration obtained after application of the protocol of plasma rich in growth factors - universal 1 (PRGF-U1) and the protocol of Anitua and Andia (PRP-A) for obtaining platelet rich plasma. Material and Method: A descriptive, cross-sectional and comparative study was carried out with a simple random probabilistic sample consisting of 16 patients who attended the Periodontics service of the Unit of Second Specialization in Stomatology of the National University of Trujillo. Five blood samples were obtained from each patient, after applying a health questionnaire to rule out any disease or drug consumption, in order to obtain the baseline platelet concentration and that obtained after PRGF-U1 and PRP-A. To compare the platelet concentrations of the two protocols, Student’s t-test was used considering a significance level of p<0.05. RESULTS: The baseline platelet concentration was 371,250 +/- 68,203 platelets/ μL, for PRGF-U1 it was 747,875 +/- 121,645 platelets/μL and for PRP-A it was 595,000 +/- 129,202 platelets/ML. A statistically significant difference (p<0.001) was found between both protocols. Conclusion: The PRGF-U1 protocol yielded a higher platelet concentration compared to the Anitua and Andia protocol.

Role of Receptor Tyrosine Kinase Signaling in Renal Fibrosis.

Renal fibrosis can be induced in different renal diseases, but ultimately progresses to end stage renal disease. Although the pathophysiologic process of renal fibrosis have not been fully elucidated, it is characterized by glomerulosclerosis and/or tubular interstitial fibrosis, and is believed to be caused by the proliferation of renal inherent cells, including glomerular epithelial cells, mesangial cells, and endothelial cells, along with defective kidney repair, renal interstitial fibroblasts activation, and extracellular matrix deposition. Receptor tyrosine kinases (RTKs) regulate a variety of cell physiological processes, including metabolism, growth, differentiation, and survival. Many studies from in vitro and animal models have provided evidence that RTKs play important roles in the pathogenic process of renal fibrosis. It is also showed that tyrosine kinases inhibitors (TKIs) have anti-fibrotic effects in basic research and clinical trials. In this review, we summarize the evidence for involvement of specific RTKs in renal fibrosis process and the employment of TKIs as a therapeutic approach for renal fibrosis.

Mechanisms of resistance to EGFR tyrosine kinase inhibitors.

Since the discovery that non-small cell lung cancer (NSCLC) is driven by epidermal growth factor receptor (EGFR) mutations, the EGFR tyrosine kinase inhibitors (EGFR-TKIs, e.g., gefitinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGFR-TKIs is inevitable due to various mechanisms, such as the secondary mutation (T790M), activation of alternative pathways (c-Met, HGF, AXL), aberrance of the downstream pathways (K-RAS mutations, loss of PTEN), impairment of the EGFR-TKIs-mediated apoptosis pathway (BCL2-like 11/BIM deletion polymorphism), histologic transformation, ATP binding cassette (ABC) transporter effusion, etc. Here we review and summarize the known resistant mechanisms to EGFR-TKIs and provide potential targets for development of new therapeutic strategies.

TSU-68 ameliorates hepatocellular carcinoma growth by inhibiting microenvironmental platelet-derived growth factor signaling.

BACKGROUND: TSU-68 is a multikinase inhibitor that targets platelet-derived growth factor receptors (PDGFRs). In the present study, we evaluated the effect of TSU-68 on the tumor-microenvironment interaction in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: HCC and fibroblast cell lines (HuH7, Hep3B, HuH1 and WI-38) were used to evaluate their interactions. Cancer characteristics were evaluated by spheroid formation and tumorigenicity in immunodeficient mice. Time-lapse image analysis was performed to monitor cell motility. RESULTS: Although PDGFA was abundantly expressed, PDGFR-α was predominantly located in the cytoplasm and was not functional in HuH7 cells. Co-culture experiments demonstrated that HCC cells induced phosphorylation of PDGFR-α in WI-38 fibroblasts and that stimulated fibroblasts, in turn, boosted the spheroid formation capacity of HCC cells. TSU-68 inhibited phosphorylation of PDGFR-α in WI-38 cells and suppressed the growth of subcutaneously co-injected HuH7/WI-38 tumor xenografts. CONCLUSION: TSU-68 inhibits stromal PDGF signaling activated by cancer cells and suppresses HCC growth.

Hamstrings anterior cruciate ligament reconstruction with and without platelet rich fibrin matrix.

PURPOSE: Anterior cruciate ligament (ACL) rupture is the most common complete ligamentous injury in the knee. Many studies explored ACL graft integration and maturation, but only a few assessed the application of platelet rich fibrin matrix (PRFM) as augmentation for ACL reconstruction. The main aim of this study was to test the PRFM augmentation in terms of graft-bone integration and knee stability. The secondary aim was to investigate patient-reported functional status. METHODS: Prospective evaluation has been done in two consecutive series of patients who underwent ACL reconstruction with semitendinosus and gracilis (STG) grafts: 14 patients were operated with PRFM augmentation and 14 patients without PRFM augmentation. Objective clinical evaluation (Rolimeter) and MRI evaluation were performed at 1 year from surgery. Subjective evaluation (IKDC) was performed pre-operatively and at 6 months, 1 and 2 years from surgery. RESULTS: A statistically significant difference was not detected between the two groups in terms of MRI and objective clinical evaluation, although PRFM-augmented patients showed a statistically significant higher clinical improvement. CONCLUSIONS: The procedure described for PRFM augmentation in ACL STG reconstruction does not improve radiologic graft integration and knee stability after 1 year and should not be used by clinicians to this purpose. However, it may result in a short-term improvement of patient-reported knee function, and future research should focus on further developing PRP treatment to optimize ACL clinical outcome. LEVEL OF EVIDENCE: III.

The effect of rotation constancy static magnetic field on the expression of BMP-2 and PDGFs during fracture healing / 中华物理医学与康复杂志

Objective To evaluate the effect rotation constancy static magnetic field(RCSMF) on the expression of bone morphogenetic protein-2 (BMP-2) and platelet-derived growth factors (PDGFs) in fracture healing, and elucidate the possible mechanism of RCSMF promoting fracture healing.Methods A total of 80 rats with femur closed fracture were randomly divided into a magnetic treatment group (M) and a control group (C).The M group was given RCSMF treatment 30 minutes per day, 6 times per week, using 0.4 T 6 Hz magnetic field, while the C group was not given any intervention.Femurs and calluses were subjected to BMP-2, PDGF-A and PDGF-B immunohistochemistry assay at 2, 3, 4 and 8 weeks after the treatment.The integrated optical density (IOD) of positive staining was calculated.Two-factor variance analysis was used to compare the main effect of time, treatment and that of their interaction.Results For both groups, the IOD of immunoreactivity of BMP-2 at 2, 3 and 4 weeks after the treatment was significantly higher than that 8 weeks after the treatment, and the value at four weeks after the intervention was also significantly higher than that at 2 weeks after it.There was a significant interaction effect of time × treatment of BMP-2 (F =3.17, P ＜ 0.05).Significant differences were observed in the IOD of positive staining PDGF-A at different time points for both groups : the value at 2 weeks after treatment was significantly higher than that at 3, 4 and 8 weeks after the treatment, and that at 3 and 4 weeks after treatment was also significantly higher than that at 8 weeks after the treatment.The IOD of positive staining PDGF-B of the M group (57.6 ± 2.1) was significantly higher than that of the C group (50.11 ± 2.22, P ＜ 0.05).There was significant difference in the IOD of positive staining PDGF-B (F =50.06 ,P ＜ 0.01) at different time points : the IOD of positive staining PDGF-B at 3 weeks after treatment was significantly higher than that at 2 and 8 weeks group after the treatment, and the value at 2 and 4 weeks after treatment was also significantly higher that at 8 weeks after the treatment.Conclusion RCSMF may elevate the expression BMP-2 and PDGF-B to promote fracture healing.

[Bone defects in revision knee arthroplasty: filling with bone allograft plus platelet-derived growth factors]. / Defectos óseos en artroplastia de revisión de rodilla tratados con aloinjerto óseo y plasma rico en plaquetas.

BACKGROUND: One of the most challenging aspects of a revision knee arthroplasty is the management of bone loss. The OBJECTIVE of the study is to show the capability to augment bone mineral density in areas with bone loss with platelet-derived growth factors. METHODS: Randomized, prospective, blinded study in patients who underwent a total knee replacement revision with tibial-damaged metaphyseal bone were randomly allocated to have a revision total knee arthroplasty and to fill the bone defects with lyophilized bone allograft mixed with platelet growth factors (experimental group, n= 9) or with lyophilized bone allograft alone (control group, n= 7). To evaluate bone mineral density between groups, dual-energy X-ray absorptiometry (DEXA) was performed preoperatively, at 1 month, 6 months and 1 year after surgery. RESULTS: The study was comprised of a total of 16 patients. We found no significant differences observed during the follow-up between groups in mineral bone density. CONCLUSIONS: Use of platelet-derived growth factors does not improve bone mineral density in patients with revision knee arthroplasty.

ANTECEDENTES: uno de los aspectos más desafiantes de la artroplastia de revisión de rodilla es el manejo de la pérdida ósea. OBJETIVO: demostrar la capacidad de incrementar la densidad mineral ósea en áreas con pérdida ósea, mediante el uso de plasma rico en plaquetas. MATERIAL Y MÉTODOS: estudio prospectivo, aleatorizado, cegado; efectuado con pacientes a quienes se realizó artroplastia de revisión de rodilla con pérdida ósea metafisiaria de tibia. Los pacientes se asignaron al azar a dos grupos para rellenar los defectos con aloinjerto óseo liofilizado con plasma rico en plaquetas (grupo experimental, n= 9), y otro grupo que sólo recibió el injerto óseo liofilizado (grupo control, n= 7). En ambos grupos la evaluación de la densidad mineral ósea se hizo con absorciometría de rayos X de energía dual (DXA) antes de la operación, al mes, seis meses, y un año después de la cirugía. RESULTADOS: se estudiaron 16 pacientes sin diferencias significativas entre ambos grupos en la densidad mineral ósea durante el periodo de seguimiento. CONCLUSIONES: el plasma rico en plaquetas no demostró incrementar la densidad mineral ósea en pacientes con defectos óseos por artroplastia de revisión de rodilla.