Sequential Delivery of Dual Growth Factors from Injectable Chitosan-Based Composite Hydrogels.

Local administration of platelet-derived growth factor-BB (PGDF-BB) and bone morphogenetic protein-2 (BMP-2) in a sequential release manner could substantially promote bone healing. To achieve this goal, a delivery system that could sustain the release of PGDF-BB and BMP-2 by way of temporal separation was developed. One type of PGDF-BB-encapsulated alginate microsphere and another type of BMP-2-encapsulated microsphere with a core-shell structure were respectively produced using emulsification methods. These two types of microspheres were then embedded into chitosan/glycerophosphate hydrogel for constructing composite gels. Some of them were found to be injectable at ambient temperature and had thermo-sensitive features near physiological temperature and pH. The optimally formulated composite gels showed the ability to control the release of PGDF-BB and BMP-2 in a sequential fashion in which PDGF-BB was released earlier than BMP-2. In vitro release patterns indicated that the release rates could be significantly regulated by varying the embedded amount of the factor-encapsulated microspheres, which can in turn mediate the temporal separation release interval between PGDF-BB and BMP-2. The released PDGF-BB and BMP-2 were detected to be bioactive based on their respective effects on Balb/c 3T3 and C2C12 cells. These results suggest that the presently developed composite gels have the potential for bone repair by synergistically utilizing the early chemotactic effect of PDGF-BB and the subsequent osteogenic and angiogenic functions of PDGF-BB and BMP-2.

Nanosphere-mediated co-delivery of VEGF-A and PDGF-B genes for accelerating diabetic foot ulcers healing in rats.

Diabetic ischemic ulcer is an intractable diabetic complication. Angiogenesis is a critical factor for wound healing in patients with diabetic foot wounds. Sustained gene delivery could be notably necessary in modulating gene expression in chronic ulcer healing and might be a promising approach for diabetic foot ulcers. In the present study, Sprague-Dawley rats were used to establish diabetic foot ulcer models by streptozotocin and skin biopsy punch. The plasmids expressing VEGF-A and PDGF-B were prepared and then incorporated with polylactic-co-glycolic acid (PLGA) nanospheres to upregulate genes expression. The aim of this study was to explore whether the engineered VEGF-A and PDGF-B based plasmid-loaded nanospheres could be upregulated in streptozotocin-induced diabetic rats and improve the wound healing. The cultured fibroblasts could be effectively transfected by means of nanosphere/plasmid in vitro. In vivo, the expression of VEGF-A and PDGF-B was significantly upregulated at full-thickness foot dorsal skin wounds and the area of ulceration was progressively and significantly reduced following treatment with nanosphere/plasmid. These results indicated that combined gene transfer of VEGF-A and PDGF-B could improve reparative processes in the wounded skin of diabetic rats and nanosphere may be a potential non-viral vector for gene therapy of the diabetic foot ulcer.

LncRNA HULC promotes epithelial and smooth-muscle-like differentiation of adipose-derived stem cells by upregulation of BMP9.

AIMS: Adipose-derived stem cells (ADSCs), a source of mesenchymal stem cells, are able to differentiate into numerous cell lineages, including epithelial and smooth muscle cells. The use of ADSCs in tissue engineering technology has become the most promising therapeutic approach for urethral reconstruction. This study aimed to explore the effect of lncRNA highly upregulated in liver cancer (HULC) on the induction of ADSCs to differentiate into epithelial and smooth-muscle-like cells. METHODS: ADSCs were isolated from a male dog, and the expression of HULC in ADSCs was overexpressed by transfection with HULC expressing vector lentivirus. The transfected ADSCs were then incubated with 5 µM ATRA or 2.5 ng/ml TGF-ß1 and 5 ng/ml PDGF-BB for 21 days. The expression of epithelial differentiation and smooth-muscle-like differentiation markers were monitored. Besides, cross-regulation between HULC and BMP9 was detected in the differentiated epithelial cells and smooth-muscle-like cells. RESULTS: HULC increased cell viability of ADSCs, but has no impact on ADSCs apoptosis. HULC promotes ADSCs to differentiate into epithelial and smooth-muscle-like cells, as evidenced by the increases in the expression of Uroplakin-II, AE1/AE3, α-SMA, SM-MHC, Calponin, and SM-22α. In addition, HULC could positively regulate BMP9, and BMP9 silence abolished HULC-promoted ADSC's differentiation. Furthermore, HULC activated Wnt/ß-catenin pathway while deactivated Notch pathway. CONCLUSION: HULC was demonstrated to be a promoter during the epithelial and smooth-muscle-like differentiation of ADSCs via the BMP9/Wnt/ß-catenin/Notch network. This study provides the first in vitro evidence that HULC-based therapy could be a valuable approach to promote urethral reconstruction.

Platelet-Derived Growth Factor-BB Lessens Light-Induced Rod Photoreceptor Damage in Mice.

Purpose: Platelet-derived growth factor (PDGF)-BB is known to have neuroprotective effects against various neurodegenerative disorders. The purpose of this study was to determine whether PDGF-BB can be neuroprotective against light-induced photoreceptor damage in mice. Methods: Mice were exposed to 8000-lux luminance for 3 hours to induce phototoxicity. Two hours before light exposure, the experimental mice were injected with PDGF-BB intravitreally, and the control mice were injected with phosphate-buffered saline. The light-exposed PDGF-BB-injected mice and saline-injected mice were evaluated electroretinographically and histologically. The site and expression levels of PDGFR-ß and PDGF-BB were determined by immunostaining and Western blotting, respectively. The effect of PDGF-BB on light-induced cone and rod photoreceptor damage was also evaluated in vitro in 661W cells, a murine cone photoreceptor cell line, and in primary retinal cell cultures. Results: An intravitreal injection of PDGF-BB significantly reduced the decrease in the amplitudes of the electroretinograms (ERGs) and the thinning of the outer nuclear layer (ONL) induced by the light exposure. It also reduced the number of TUNEL-positive cells in the ONL. PDGFR-ß was expressed in the rod outer segments (OSs) but not the cone OSs. The levels of PDGF-BB and PDGFR-ß were decreased after light irradiation. In addition, PDGF-BB had protective effects against light-induced damage to cells of rod photoreceptors but had no effect on the 661W cells in vitro. Conclusions: These findings indicate that PDGF-BB reduces the degree of light-induced retinal damage by activating PDGFR-ß in rod photoreceptors. These findings suggest that PDGF-BB could play a role in the prevention of degeneration in eyes susceptible to phototoxicity.

Comparative Study of rhPDGF-BB Plus Equine-Derived Bone Matrix Versus rhPDGF-BB Plus ß-TCP in the Treatment of Periodontal Defects.

The purpose of this study was to evaluate the efficacy and safety of equine-derived bone matrix as a carrier for recombinant human platelet-derived growth factor BB (rhPDGF-BB) versus beta-tricalcium phosphate (ß-TCP) for the treatment of intraosseous periodontal defects in adult patients. This study was performed on 32 adults with advanced periodontal disease. Eligible subjects were randomized in 1:1 ratio into a test (rhPDGF-BB-coated equine-derived bone matrix) or control group (rhPDGF-BB-coated ß-TCP). Probing pocket depth (PD), clinical attachment level (CAL), gingival recession (GR), and defect depth on radiographs were measured at 2 weeks before surgery, on the day of surgery (DOS), and 6 months postsurgery (6MPS). The clinical and radiographic data were analyzed over the test period. Statistically significant PD reductions and CAL gain between baseline and 6MPS and between ODS and 6MPS were seen in both groups (P < .01). No statistically significant differences in PD reduction were found between groups. However, the test group showed significant CAL gain between DOS and 6MPS. The radiographic bone level change was statistically significant compared to baseline (P < .01) in both groups. The results suggested that equine-derived bone matrix is a viable, effective, and safe carrier scaffold for rhPDGF in periodontal defects.

Phenotypic switching prevention and proliferation/migration inhibition of vascular smooth muscle cells by the ruthenium nitrosyl complex trans-[Ru(NO)Cl(cyclam](PF6 )2.

OBJECTIVES: Vascular smooth muscle cell (VSMC) migration and proliferation at sites of vascular injury are both critical steps in the development of intimal hyperplasia (IH). Local delivery of nitric oxide (NO) largely prevents these events. Among the NO donors, tetraazamacrocyclic nitrosyl complexes, such as trans-[Ru(NO)Cl(cyclam)](PF6 )2 (cyclamNO), gained attention for their features, which include the possibility of being embedded in solid matrices, and ability to participate in a nitrite/NO catalytic conversion cycle. METHODS: Methods used to evaluate cyclamNO activity: safety margin by NR and MTT; cell proliferation by 3H-thymidine incorporation and proliferating cell nuclear antigen (PCNA) expression; antimigratory properties by transwell and wound healing; prevention of cell phenotypic switching under platelet-derived growth factor type BB (PDGF-BB) stimuli by analysis of alpha smooth muscle actin (α-SMA) expression. KEY FINDINGS: Cell proliferation and migration induced by PDGF-BB were significantly inhibited by cyclamNO. The ~60% reduction on expression of contractile protein α-SMA induced by PDGF-BB revealed VSMC phenotypic switching which is significantly prevented by cyclamNO. Compared to the NO donor sodium nitroprusside, cyclamNO showed to be significantly less cytotoxic. CONCLUSIONS: With great potential to maintain VSMC functionality and prevent IH-associated events, cyclamNO might be a promissory drug for several applications in cardiovascular medicine, as in stents.

Application of platelet derived growth factor-BB and diabetic wound healing: the relationship with oxidative events.

The reasons that cause delay in wound healing in diabetes are a decrease in the level of growth factors secretion, an increase in the destruction of growth factors and in oxidative stress. Platelet derived growth factor (PDGF) is one of the important growth factors that play a role in all phases of wound healing. This study investigates time-dependent effects of topically PDGF-BB administration on oxidative events on the healing of dorsolateral-excisional wounds in diabetic rats. Forty-two female Wistar-albino rats with streptozotocin-induced diabetes were divided into four groups: control group, untreated group, chitosan-treated group, chitosan + PDGF-BB-treated group. Two identical full-thickness excisional skin wounds were made under anaesthesia in all rats except for the control group. In the PDGF-BB-treated and chitosan-treated groups, the wounds were treated topically PDGF-BB (7 ng/mL, single daily dose) and blank chitosan gel (equal amount) after wounding, respectively. After these administrations, on day 3 and day 7 of wound healing, rats were sacrificed. Thiobarbituric acid reactive substances, glutathione, nitric oxide, ascorbic acid levels, and superoxide dismutase activity in wound tissues were spectrophotometrically measured. PDGF-BB administration significantly increased TBARS levels and non-enzymatic antioxidant levels in early phase of diabetic wound healing. PDGF-BB dramatically reduced NOx levels on day 3 and sharply increased NOx levels on day 7 of wound healing. Consequently, PDGF-BB administration can be effective on oxidative balance in the early phase of diabetic wound healing.

Evaluation of Recombinant Human FGF-2 and PDGF-BB in Periodontal Regeneration: A Systematic Review and Meta-Analysis.

The prognosis for successful treatment of periodontal diseases is generally poor. Current therapeutic strategies often fail to regenerate infected periodontium. Recently an alternative strategy has been developed that combines conventional treatment with the application of recombinant human growth factors (rhGFs). But ambiguities in existed studies on the clinical efficacy of rhGFs do not permit either the identification of the specific growth factors effective for therapeutic interventions or the optimal concentration of them. Neither is it known whether the same rhGF can stimulate regeneration of both soft tissue and bone, or whether different patient populations call for differential use of the growth factors. In order to explore these issues, a meta-analysis was carried out. Particular attention was given to the therapeutic impact of fibroblast growth factor 2(FGF-2) and platelet derived growth factor BB (PDGF-BB). Our findings indicate that 0.3% rhFGF-2 and 0.3 mg/ml rhPDGF-BB show a greater capacity for periodontal regeneration than other concentrations and superiority to control groups with statistical significance. In the case of patients suffering only from gingival recession, however, the application of rhPDGF-BB produces no significant regenerative advantage. The findings of this study can potentially endow clinicians with guidelines for the appropriate application of these two rhGFs.

A multifunctional bioactive material that stimulates osteogenesis and promotes the vascularization bone marrow stem cells and their resistance to bacterial infection.

The main limitation of tissue engineering lies in the inability to stimulate osteogenesis, angiogenesis of stem cells and broad-spectrum antimicrobial activity. However, the development of multifunctional bioactive materials with these capabilities remains a great challenge. In this study, we prepared mesoporous silica nanoparticles encapsulated with silver nanocrystals (AG-MSN) with uniform sphere size and mesopores. Platelet-derived growth factor BB (PDGF-BB) was effectively loaded in the AG-MSN mesopores (P-AG-MSN). The silicon ions (Si) released by P-AG-MSN stimulate osteogenic differentiation of bone marrow stromal cells (BMSC) by activating the alkaline phosphatase (ALP) activity of bone-related genes and increasing protein (OCN, RUNX2 and OPN) expression. Ag+ ions could be slowly released from the interior of the shell, highlighting their durable antibacterial activity. The sustained release of PDGF-BB from P-AG-MSN stimulated the angiogenic differentiation of BMSC, as indicated by the enhanced secretion of vascular endothelial growth factor (VEGF), HIF-1α, HGF and ANG-1 and protein expression. Our results show that P-AG-MSN can clearly promote BMSC osteostimulation and vascularization. This research serves as a preliminary study of the utilization of this multifunctional mixture to fabricate a new active biological scaffold that integrates BMSC osteostimulation, vascularization and bactericidal effects by 3D printing technology.

Enzymatic in situ formed hydrogel from gelatin-tyramine and chitosan-4-hydroxylphenyl acetamide for the co-delivery of human adipose-derived stem cells and platelet-derived growth factor towards vascularization.

An injectable, in situ forming hydrogel system capable of co-delivering human adipose-derived stem cells (hADSC) and platelet-derived growth factor (PDGF) was investigated as a new system for tissue engineering, envisaged to support vascularization. The system consists of tyramine-conjugated gelatin and hydroxyphenyl acetamide chitosan derivative. Both are soluble and stable at physiologic conditions, which is a key factor for retaining viable cells and active growth factor. In situ gelation involved enzymatic crosslinking using horseradish peroxidase as a catalyst and hydrogen peroxide as an oxidant. Gel formation occurred within 30-90 s by controlling the concentration of polymers. PDGF release showed adequate release kinetics within the intended period of time and hADSC showed good compatibility with the hydrogel formulation based on the in vitro assay and subcutaneous implantation into BALB/c-nu/nu nude female mice. Immunohistochemical analysis confirmed viability of delivered hADSC. Histological analysis showed no immune reaction and confirmed blood vessel formation. The results implicate the hydrogel as a promising delivery vehicle or carrier of both cell and growth factor, which support vascularization for tissue engineering applications.

Injectable Recombinant Human Platelet-derived Growth Factor in Collagen Carrier for Hindfoot Fusion.

Arthrodesis of the hindfoot is a common procedure for degenerative joint disease and/or severe deformity. Nonunion is a common complication from this procedure, causing an increased burden to the patient and health care system, often resulting in the need for revision surgery. Recombinant human platelet-derived growth factor (rhPDGF) has been shown to be a safe and effective tool to enhance arthrodesis rates in hindfoot surgery while avoiding the potential morbidity of bone grafting. This article provides a review of the role of rhPDGF in hindfoot fusions, and the surgical technique for performing an rhPDGF enhanced double-arthrodesis through a medial approach.

Evodiamine inhibits PDGF­BB­induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress.

Vascular smooth muscle cell (VSMC) proliferation is a key event in the development of in­stent restenosis. Evodiamine is an indole alkaloid extracted from the Chinese medicine, evodia, and has been shown to inhibit tumor cell proliferation and protect the cardiovascular system. However, whether evodiamine affects VSMC proliferation remains to be elucidated. Therefore, the present study examined the effects and the mechanisms of action of evodiamine on the proliferation of rat VSMCs. The cells were treated with evodiamine alone or in combination with platelet­derived growth factor­BB (PDGF­BB) stimulation. It was found that evodiamine inhibited PDGF­BB­induced VSMC proliferation in a dose­dependent manner, without inducing cell death. Evodiamine also retarded cell cycle progression, evidenced by the suppression of the expression of cell cycle­promoting cyclin proteins and cyclin­dependent kinases. In addition, evodiamine attenuated the PDGF­BB­induced phosphorylation of mitogen­activated protein kinases p38 and extracellular signal­regulated kinases 1/2, however, it had no effect on the phosphorylation of Akt. Evodiamine also inhibited the increase of reactive oxygen species generation and upregulated the mRNA expression levels of genes encoding antioxidant enzymes. These findings provide important insights into the mechanisms underlying the vasoprotective actions of evodiamine and suggest that it may be a useful therapeutic agent for the treatment of vascular occlusive disease.

Platelet-derived growth factor-BB attenuates titanium-particle-induced osteolysis in vivo.

Inflammation and osteoclastogenesis play critical roles in wear-particle-induced periprosthetic osteolysis (WPO). Platelet-derived growth factor-BB (PDGF-BB) could promote osteogenesis and inhibit inflammatory response. The aim of this study was to investigate the impact of PDGF-BB on WPO. Mice were divided into four groups, namely, sham, vehicle, low-, and high-dose PDGF-BB groups. Mice in the rhPDGF-BB groups were treated with PDGF-BB at 0.25 or 1 mg/ml/kg/day. Mice in the sham and vehicle groups received PBS daily. Two weeks after surgery, calvariae were harvested. Immunohistochemical analysis and µ-CT showed that PDGF-BB significantly reduced osteoclast formation and bone resorption. ELISA showed that rhPDGF-BB decreased the secretion of TNF-α, IL-1ß, and IL-6. Western blotting revealed that rhPDGF-BB stimulated the expression of osteocalcin and osteoprotegerin. Furthermore, more VEGF and CD31 proteins were observed due to PDGF-BB by immunofluorescence. In conclusion, these findings suggest that rhPDGF-BB represents a potential treatment for WPO.

Controlled delivery of platelet-derived growth factor-BB from injectable microsphere/hydrogel composites.

Platelet-derived growth factor-BB (PGDF-BB) loaded gelatin microspheres with an average size of about 2µm was incorporated into chitosan/silk fibroin/glycerophosphate (GP) solutions to prepare composites. The formulated composite solutions were able to form into hydrogels in a temperature range between 32 and 37°C at a pH of ca.7. They had good fluidity at 25°C and showed shear-thinning features at both 25 and 37°C, revealing that they are injectable at room temperature. Elastic modulus of some composites at 37°C was about 10-fold higher than that of chitosan/GP gel, confirming that these composites behave like mechanically strong gels. Optimal composites showed abilities to administrate PDGF-BB release in an approximately linear manner up to 5 weeks. The PDGF-BB release could be regulated by the PDGF-BB load and the silk fibroin content in the composites in an individual or cooperative way. In vivo degradation of composites demonstrated that some of them had markedly enhanced degradation endurance as compared to the chitosan/GP gel. PDGF-BB-stimulated DNA synthesis in Balb/c 3T3 fibroblasts and PDGF-BB-induced cell migration suggested that the bioactivity of released PDGF-BB was well retained.

Local administration of platelet-derived growth factor B (PDGFB) improves follicular development and ovarian angiogenesis in a rat model of Polycystic Ovary Syndrome.

Alterations in ovarian angiogenesis are common features in Polycystic Ovary Syndrome (PCOS) patients; the most studied of these alterations is the increase in vascular endothelial growth factor (VEGF) production by ovarian cells. Platelet-derived growth factor B (PDGFB) and D (PDGFD) are decreased in follicular fluid of PCOS patients and in the ovaries of a rat model of PCOS. In the present study, we aimed to analyze the effects of local administration of PDGFB on ovarian angiogenesis, follicular development and ovulation in a DHEA-induced PCOS rat model. Ovarian PDGFB administration to PCOS rats partially restored follicular development, decreased the percentage of cysts, increased the percentage of corpora lutea, and decreased the production of anti-Müllerian hormone. In addition, PDGFB administration improved ovarian angiogenesis by reversing the increase in periendothelial cell area and restoring VEGF levels. Our results shed light into the mechanisms that lead to altered ovarian function in PCOS and provide new data for potential therapeutic strategies.

Bioactive, Elastic, and Biodegradable Emulsion Electrospun DegraPol Tube Delivering PDGF-BB for Tendon Rupture Repair.

Healing of tendon ruptures represents a major challenge in musculoskeletal injuries and combinations of biomaterials with biological factors are suggested as viable option for improved healing. The standard approach of repair by conventional suture leads to incomplete healing or rerupture. Here, a new elastic type of DegraPol® (DP), a polyester urethane, is explored as a delivery device for platelet-derived growth factor-BB (PDGF-BB) to promote tendon healing. Using emulsion electrospinning as an easy method for incorporation of biomolecules within polymers, DegraPol® supports loading and release of PDGF-BB. Morphological, mechanical and delivery device properties of the bioactive DP scaffolds, as well as differences arising due to different electrospinning parameters are studied. Emulsion electrospun DP scaffolds result in thinner fibers than pure DP scaffolds and experience decreased strain at break [%], but high enough for successful surgeon handling. PDGF-BB is released in a sustained manner from emulsion electrospun DP, but not completely, with still large amount of it being inside the polymeric fibers after 30 d. In vitro studies show that the bioactive scaffolds promote tenocyte proliferation in serum free and serum(+) conditions, demonstrating the potential of this surgeon-friendly bioactive delivery device to be used for tendon repair.

Combined delivery of PDGF-BB and BMP-6 for enhanced osteoblastic differentiation.

Natural microenvironment during bone tissue regeneration involves integration of multiple biological growth factors which regulate mitogenic activities and differentiation to induce bone repair. Among them platelet derived growth factor (PDGF-BB) and bone morphogenic protein-6 (BMP-6) are known to play a prominent role. The aim of this study was to investigate the benefits of combined delivery of PDGF-BB and BMP-6 on proliferation and osteoblastic differentiation of MC3T3-E1 preosteoblastic cells. PDGF-BB and BMP-6 were loaded in gelatin and poly (3-hydroxybutyric acid-co-3-hydroxyvaleric acid) particles, respectively. The carrier particles were then loaded into 3D chitosan matrix fabricated by freeze drying. The fast release of PDGF-BB during 7 days was accompanied by slower and prolonged release of BMP-6. The premising release of mitogenic factor PDGF-BB resulted in an increased MC3T3-E1 cell population seeded on chitosan scaffolds. Osteogenic markers of RunX2, Col 1, OPN were higher on chitosan scaffolds loaded with growth factors either individually or in combination. However, OCN expression and bone mineral formation were prominent on chitosan scaffolds incorporating PDGF-BB and BMP-6 as a combination.

[Platelet-derived growth factor-BB induces phenotypic transformation of corpus cavernosum smooth muscle cells in SD rats].

OBJECTIVE: To evaluate the effect of the platelet-derived growth factor-BB (PDGF-BB) on the phenotypic transformation of corpus cavernosum smooth muscle cells (CCSMC) in SD rats. METHODS: CCSMCs were primarily cultured in the modified tissue sticking medium and subjected to immunofluorescence assay. The cells were divided into a blank control and four PDGF-BB groups, the latter exposed to 5, 10, 20, and 40 ng/ml of PDGF-BB, respectively, for 24 hours, and the cells in the 20 ng/ml PDGF-BB group treated for 24, 48, and 72 hours. The the relative expressions of α-SMA, SMMHC, calponin, and OPN mRNA were determined by real-time fluorescence quantitative RT-PCR (qRT-PCR). RESULTS: The α-SMA positive rate of the CCSMCs was over 95%. Compared with the blank control group, the expression levels of α-SMA, SMMHC, and calponin mRNA were significantly decreased (P < 0.05) while that of OPN mRNA remarkably increased (P < 0.05) in the PDGF-BB groups. The 20 ng/ml PDGF-BB group also showed significantly downregulated expressions of α-SMA, SMMHC, and calponin mRNA (P < 0.05) and upregulated expression of OPN mRNA (P < 0.05) at 24, 48, and 72 hours. CONCLUSION: PDGF-BB can induce the transformation of the phenotype of CCSMCs in SD rats from the contractile to the synthetic type.

Consecutive Case Series Using a Composite Allograft Containing Mesenchymal Cells with an Amnion-Chorion Barrier to Treat Mandibular Class III/IV Furcations.

This retrospective case series describes a layered regenerative approach for five Class III and one borderline Class IV furcation, involving treatment consisting of root management that included conditioning with tetracycline solution followed by the topical application of recombinant platelet-derived growth factor BB. A composite allograft with mesenchymal stem cells was subsequently placed into the furcation and covered by a barrier derived from human amnion-chorion with flaps advanced to completely cover the site. Three furcations, including the one diagnosed as Class IV, had complete closure, two were converted to Class I, and in one instance, there was no improvement. This regenerative algorithm for mandibular Class III furcations may present the potential to save these teeth by altering the prognosis, which has traditionally been poor to hopeless, resulting in many of these teeth routinely being extracted.

BMP-2, PDGF-BB, and bone marrow mesenchymal cells in a macroporous ß-TCP scaffold for critical-size bone defect repair in rats.

The aim of this work was to study the bone repair induced by bone morphogenetic protein-2 (BMP-2), rat mesenchymal stem cells (rMSCs), and platelet-derived growth factor (PDGF-BB) incorporated in a macroporous beta-tricalcium phosphate (ß-TCP) system fabricated by robocasting, and to identify the most beneficial combination in a critical rat calvaria defect. BMP-2 was formulated in microspheres to provide a prolonged, local concentration, whereas PDGF-BB, which acts during the initial stage of defect repair, was incorporated in a thin layer of crosslinked alginate. Approximately 80% of PDGF-BB and 90% of BMP-2 were released into the defect during the first 2 d and 3 weeks, respectively. Histological analyses indicated a minor synergistic effect in the BMP-2-MSC groups. In contrast, significant antagonism was found with combined BMP-2 and PDGF-BB defect treatment. The high-grade repair induced by BMP-2 rules out any advantage from combining BMP-2 with PDGF-BB or MSCs, at least with this scaffold and defect model.