OBJECTIVE: Periodontitis is an inflammatory condition induced by subgingival bacterial dysbiosis, resulting in inflammatory-mediated destruction of tooth-supporting structures, potentially leading to the formation of infrabony defects. This case report describes the treatment of a patient who presented with a combination 1-2-wall defect on tooth 21. To maintain the residual periodontal attachment and minimize esthetic consequences, a regenerative approach was performed using recombinant human platelet-derived growth factor-BB (rh-PDGF-BB) and β-tricalcium phosphate (β-TCP).
METHODS: At the time of postscaling/root planing reevaluation, a 34-year-old Asian male initially diagnosed with molar/incisor pattern stage III grade C periodontitis exhibited a 6-mm residual probing depth on the mesiopalatal aspect of tooth 21. Periodontal regenerative surgery was performed using rh-PDGF-BB with β-TCP, without the use of a membrane.
RESULTS: At the 1-year follow-up, a significant reduction in probing depth and radiographic evidence of bone fill were observed. Additionally, re-entry surgery for implant placement at site tooth 23 confirmed bone fill in the defect on tooth 21.
CONCLUSIONS: These results demonstrate the efficacy of rh-PDGF-BB with β-TCP in enhancing periodontal regeneration and support its use as a treatment option when treating poorly contained infrabony defects in the esthetic zone.

Non-union during healing of bone fractures affects up to ~5% of patients worldwide. Given the success of recombinant human platelet-derived growth factor-B chain homodimer (rhPDGF-BB) in promoting angiogenesis and bone fusion in the hindfoot and ankle, rhPDGF-BB combined with bovine type I collagen/β-TCP matrix (AIBG) could serve as a viable alternative to autografts in the treatment of non-unions. Defects (~2 mm gaps) were surgically induced in tibiae of skeletally mature New Zealand white rabbits. Animals were allocated to one of four groups-(1) negative control (empty defect, healing for 8 weeks), (2 and 3) acute treatment with AIBG (healing for 4 or 8 weeks), and (4) chronic treatment with AIBG (injection 4 weeks post defect creation and then healing for 8 weeks). Bone formation was analyzed qualitatively and semi-quantitatively through histology. Samples were imaged using dual-energy X-ray absorptiometry and computed tomography for defect visualization and volumetric reconstruction, respectively. Delayed healing or non-healing was observed in the negative control group, whereas defects treated with AIBG in an acute setting yielded bone formation as early as 4 weeks with bone growth appearing discontinuous. At 8 weeks (acute setting), substantial remodeling was observed with higher degrees of bone organization characterized by appositional bone growth. The chronic healing, experimental, group yielded bone formation and remodeling, with no indication of non-union after treatment with AIBG. Furthermore, bone growth in the chronic healing group was accompanied by an increased presence of osteons, osteonal canals, and interstitial lamellae. Qualitatively and semiquantitatively, chronic application of AI facilitated complete bridging of the induced non-union defects, while untreated defects or defects treated acutely with AIBG demonstrated a lack of complete bridging at 8 weeks.

Chronic wounds have emerged as an increasingly critical clinical challenge over the past few decades, due to their increasing incidence and socioeconomic burdens. Platelet-derived growth factor (PDGF) plays a pivotal role in regulating processes such as fibroblast migration, proliferation, and vascular formation during the wound healing process. The delivery of PDGF offers great potential for expediting the healing of chronic wounds. However, the clinical effectiveness of PDGF in chronic wound healing is significantly hampered by its inability to maintain a stable concentration at the wound site over an extended period. In this study, a controlled PDGF delivery system based on nanocapsules is proposed. In this system, PDGF is encapsulated within a degradable polymer shell. The release rate of PDGF from these nanocapsules can be precisely adjusted by controlling the ratios of two crosslinkers with different degradation rates within the shells. As demonstrated in a diabetic wound model, improved therapeutic outcomes with PDGF nanocapsules (nPDGF) treatment are observed. This research introduces a novel PDGF delivery platform that holds promise for enhancing the effectiveness of chronic wound healing.

Contemporary oral tissue engineering strategies involve recombinant human growth factor approaches to stimulate diverse cellular processes including cell differentiation, migration, recruitment, and proliferation at grafted areas. Recombinant human growth factor applications in oral hard and soft tissue regeneration have been progressively researched over the last 25 years. Growth factor-mediated surgical approaches aim to accelerate healing, tissue reconstruction, and patient recovery. Thus, regenerative approaches involving growth factors such as recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and recombinant human bone morphogenetic proteins (rhBMPs) have shown certain advantages over invasive traditional surgical approaches in severe hard and soft tissue defects. Several clinical studies assessed the outcomes of rhBMP-2 in diverse clinical applications for implant site development and bone augmentation. Current evidence regarding the clinical benefits of rhBMP-2 compared to conventional therapies is inconclusive. Nevertheless, it seems that rhBMP-2 can promote faster wound healing processes and enhance de novo bone formation, which may be particularly favorable in patients with compromised bone healing capacity or limited donor sites. rhPDGF-BB has been extensively applied for periodontal regenerative procedures and for the treatment of gingival recessions, showing consistent and positive outcomes. Nevertheless, current evidence regarding its benefits at implant and edentulous sites is limited. The present review explores and depicts the current applications, outcomes, and evidence-based clinical recommendations of rhPDGF-BB and rhBMPs for oral tissue regeneration.

BACKGROUND: Due to the constraints surrounding autograft bone, surgeons have turned to osteoinductive agents to augment spinal fusion. Reports of complications and questionable efficacy slowed the adoption of these alternatives. Recombinant human platelet-derived growth factor B homodimer (rhPDGF-BB) has been Food and Drug Administration (FDA)-approved (Augment) to promote fusion in other areas of orthopedics, but its characterization in spine fusion has not yet been tested. The purpose of this study is to characterize the host response to PDGF-BB in vivo.
METHODS: Eighty female Fischer rats underwent L4-5 posterolateral fusion using one of four implant types: (a) iliac crest syngeneic allograft harvested from syngeneic donors, (b) β-TCP/bovine collagen matrix (β-TCP/Col) with sodium acetate buffer, (c) β-TCP/Col with 0.3 mg/mL \"low dose,\" or (d) β-TCP/Col with 3.0 mg/mL \"high dose\" of rhPDGF-BB. Animals underwent magnetic resonance imaging (MRI) and serum cytokine quantification at 4, 7, 10, and 21 days, postoperatively. Tissues were processed for immunofluorescence staining for Ki67 and von Willebrand factor (vWF) to assess neovascularization.
RESULTS: MRI demonstrated no differences in fluid accumulation among the four treatment groups at any of the time points. Serum cytokine analysis showed no clinically significant differences between treatment groups in 20 of the 27 cytokines. Inflammatory cytokines IFN-γ, IL-1β, IL-18, MCP-1, MIP-1α, TNF-α were not induced by rhPDGF-BB. Histology showed no differences in cell infiltration, and Ki67 and vWF immunofluorescence staining was similar among groups.
CONCLUSIONS: rhPDGF-BB delivered with a β-TCP/Col matrix exerts no exaggerated systemic or local host inflammatory response when compared to iliac crest syngeneic allograft bone or the control carrier. rhPDGF-BB mixed with a β-TCP/Col matrix could be a viable and safe biologic alternative to syngeneic allograft in spine fusion. Further studies need to be performed to evaluate efficacy in this setting.

Drugs that can induce mesenchymal stem cell (MSC) mobilization from synovium into synovial fluid will enable regenerative medicine in joints without use of exogenous MSCs. An in vitro synovial MSC migration model had previously been developed for screening but had problems in practical application. We herein developed a novel in vitro model, explored cytokines for synovial MSC mobilization with this model, and verified whether MSCs in synovial fluid increase following intra-articular injection of the cytokine.
Human synovial MSCs embedded in a mixture of Matrigel and type 1 collagen hydrogel were placed on a culture insert and then put in medium containing migration factor. Of the six cytokines, we identified the one that mobilizes the highest number of MSCs. PDGF-BB or PBS was injected into rat knees, and 48 h later, synovial fluid was collected and cultured. The cells were examined for MSC properties.
PDGF-BB was the most effective for synovial MSC mobilization among six cytokines. The effect of PDGF-BB was inhibited by a PRGFR inhibitor. Injection of PDGF-BB into rat knees increased colony-forming cells in the synovial fluid. These cells had surface epitopes and multipotency comparable to MSCs and a higher capacity for proliferation, colony formation, and chondrogenesis.
This novel in vitro model recapitulated the migration of MSCs from synovium into synovial fluid. Our exploration of cytokines revealed that PDGF-BB strongly induced in vitro synovial MSC migration, while intra-articular injection of PDGF-BB increased in vivo MSC numbers in synovial fluid in rats.

BACKGROUND: Recession defects are typically characterized by loss of periodontal attachment, including gingiva, periodontal ligament, alveolar bone, and cementum. Numerous techniques have been developed for treatment of these defects using soft-tissue grafting procedures with autogenous and allograft materials that generally heal with root coverage and repair of the defects. This case presentation illustrates a technique using a particulate carrier saturated with recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and coronally advanced gingival flaps to cover recession defects. Additionally, other scientific evidence from previous studies suggests that this technique may lead to periodontal regeneration, including cementum, periodontal ligament, and alveolar bone over previously exposed roots, which might be preferable to other methods that lead to periodontal repair.
METHODS: This article illustrates a technique to coronally position flaps in combination with rhPDGF-BB-saturated particulate graft material. Results show significant root coverage with excellent color and texture match to adjacent tissues. Additionally, the alveolus appeared thicker than non-treated areas, suggesting appositional augmentation of the sites. Human histologic investigation of this technique in other studies confirms that periodontal regeneration can occur with this technique.
CONCLUSIONS: Coronally positioned flaps over rhPDGF-BB-soaked human freeze-dried bone allograft, termed \"recession regeneration,\" can result in significant root coverage with excellent esthetics, even in demanding cases. Surgical reentry of one case shows significant regeneration of buccal alveolar bone over the previously exposed root surfaces, consistent with periodontal regeneration that is not ordinarily observed with other root coverage techniques unless biologic modifiers or cell occlusive barrier membranes are used.

BACKGROUND: The availability of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) plus β-tricalcium phosphate (β-TCP) for periodontal therapeutic use resulted from a large-scale, prospective, masked, randomized clinical trial. This pivotal trial indicated that this combination can safely and effectively be used to treat advanced periodontal osseous defects. Previous reports demonstrated significant gain in clinical attachment level, linear bone gain, and percentage bone fill after 6 months. Subsequent evaluation of selected cases 24 months after treatment indicated the clinical gains were maintainable. Furthermore, there appeared to be substantial increase in linear bone gain and percentage bone fill. Radiographically, there was increased radiopacity and bone trabeculation, suggesting bone maturation.
METHODS: This report presents representative cases from the rhPDGF-BB plus β-TCP pivotal clinical trial after 60 months. Maximal regenerative results were achieved after 12 months and maintained ≥5 years. Sites treated with rhPDGF-BB plus β-TCP were generally healthy, with no evidence of ankylosis, root resorption, or abnormal tissue reaction. However, a limited number of cases deteriorated, suggesting that smoking and poor self/supportive care compliance can adversely affect periodontal regenerative results.
CONCLUSIONS: The use of rhPDGF-BB plus β-TCP was safe and effective in the treatment of periodontal osseous defects. The regenerated results are maintainable ≥5 years, with adverse events attributable to the treatment.

Periodontal regeneration is preferred over tissue repair and is accomplished through the exclusion of epithelial tissues, which allows cementum, bone, and connective tissue to repopulate the wound. Recently, biologic materials have emerged as adjuncts to aid in regeneration by augmenting the events of wound healing in the area. A review of biologic agents was conducted using the following MeSH terms: guided tissue regeneration, intercellular signaling peptides and proteins, and biologic factors. Enamel matrix derivative (EMD), platelet-derived growth factor (PDGF), platelet-rich plasma, bone morphogenetic proteins (BMPs), fibroblast growth factor (FGF), and parathyroid hormone (PTH) have all shown promise in promoting hard- or soft-tissue regeneration. No biologic agent is ideal for all clinical situations so the clinician must evaluate each situation to identify the best indication for its usage. Currently, EMD and PDGF have Food and Drug Administration approval for periodontal regeneration, whereas BMP-2 is approved for bone augmentation. FGF and PTH do not have Food and Drug Administration approval for periodontal applications and so their clinical usage is not indicated.

BMPs are used in various clinical applications to promote bone formation. The limited success of the BMPs in clinical settings and supraphysiological doses required for their effects prompted us to evaluate the influence of other signaling molecules, specifically platelet-derived growth factor (PDGF) on BMP2-induced osteogenesis. Periosteal cells make a major contribution to fracture healing. We detected broad expression of PDGF receptor beta (PDGFRβ) within the intact periosteum and healing callus during fracture repair. In vitro, periosteum-derived progenitor cells were highly responsive to PDGF as demonstrated by increased proliferation and decreased apoptosis. However, PDGF blocked BMP2-induced osteogenesis by inhibiting the canonical BMP2/Smad pathway and downstream target gene expression. This effect is mediated via PDGFRβ and involves ERK1/2 MAPK and PI3K/AKT signaling pathways. Therapeutic targeting of the PDGFRβ pathway in periosteum-mediated bone repair might have profound implications in the treatment of bone disease in the future.