scholarly journals Clinical application of injectable growth factor for bone regeneration: a systematic review

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Yutaka Kuroda ◽  
Toshiyuki Kawai ◽  
Koji Goto ◽  
Shuichi Matsuda

Abstract Bone regeneration has been the ultimate goal in the field of bone and joint medicine and has been evaluated through various basic research studies to date. Translational research of regenerative medicine has focused on three primary approaches, which are expected to increase in popularity: cell therapy, proteins, and artificial materials. Among these, the local injection of a gelatin hydrogel impregnated with the protein fibroblast growth factor (FGF)-2 is a biomaterial technique that has been developed in Japan. We have previously reported the efficacy of gelatin hydrogel containing injectable FGF-2 for the regenerative treatment of osteonecrosis of the femoral head. Injectable growth factors will probably be developed in the future and gain popularity as a medical approach in various fields as well as orthopedics. Several clinical trials have already been conducted and have focused on this technique, reporting its efficacy and safety. To date, reports of the clinical application of FGF-2 in revascularization for critical limb ischemia, treatment of periodontal disease, early bone union for lower limb fracture and knee osteotomy, and bone regeneration for osteonecrosis of the femoral head have been based on basic research conducted in Japan. In the present report, we present an extensive review of clinical applications using injectable growth factors and discuss the associated efficacy and safety of their administration.

2021 ◽  
pp. 5-17
Author(s):  
V.A. Konev ◽  
◽  
D.V. Labutin ◽  
S.A. Bozhkova ◽  
◽  
...  

Analysis of scientifi c publications devoted to effi cacy assessment and experimental justifi cation of cell technology and growth factors application for osteogenesis stimulation in clinical practice of traumatologists-orthopaedists.The search was performed for papers published in PubMed and E-library digital databases within the period of 2010-2020. The search filter was set to explore randomised clinical trials. Th e key words were: “platelet growth factor OR vascular endothelial growth factor OR bone morphogenetic proteins OR autologous bone marrow stromal cells AND bone defect AND human”. Works dated 2010-2020 were selected for analysis of experimental studies using the following key word combinations: “mesenchymal stromal cells AND osteogenesis OR bone regeneration”, “growth factors AND mesenchymal stromal cells AND osteogenesis OR bone regeneration”. In addition, essential literatures describing properties of multipotent mesenchymal stromal cells (MSCs) were cited as well as issues in their osteogenic diff erentiation. Despite the great number of experimental works related to cell technology application for bone growth stimulation, a large variety of unresolved issues associated with optimal means to create such cells, their cultivation and combined application with morphogenetic proteins and growth factors remains. Clinical application of rhBMP-2, PDGF has demonstrated effi cacy in complex treatment of patients with bone defects. Th erewith, growth factors may be effi caciously used in diff erent combinations with MSCs. In a number of cases, application of implants enriched with growth factors may become an alternative for autogenic grafts. To the present day, there is crucial defi cit in the number of works presenting results of randomised controlled clinical trials devoted to stimulation of bone tissue repair. The controversial results of the publications analysed may be based on a low number of patients enrolled. With consideration for active development of reparative medicine as a whole, further investigation of possibilities in bone growth stimulation with local application of cell-engineering constructions is considered to be a promising trend for traumatology and orthopaedics.


2016 ◽  
Vol 45 (4) ◽  
pp. 954-960 ◽  
Author(s):  
Matthias Kieb ◽  
Frank Sander ◽  
Cornelia Prinz ◽  
Stefanie Adam ◽  
Anett Mau-Möller ◽  
...  

Background: Platelet-rich plasma (PRP) is widely used in sports medicine. Available PRP preparations differ in white blood cell, platelet, and growth factor concentrations, making standardized research and clinical application challenging. Purpose: To characterize a newly standardized procedure for pooled PRP that provides defined growth factor concentrations. Study Design: Controlled laboratory study. Methods: A standardized growth factor preparation (lyophilized PRP powder) was prepared using 12 pooled platelet concentrates (PCs) derived from different donors via apheresis. Blood samples and commercially available PRP (SmartPrep-2) served as controls (n = 5). Baseline blood counts were analyzed. Additionally, single PCs (n = 5) were produced by standard platelet apheresis. The concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor AB (PDGF-AB), transforming growth factor β1 (TGF-β1), insulin-like growth factor 1 (IGF-1), interleukin (IL)–1α, IL-1β, and IL-1 receptor agonist (IL-1RA) were analyzed by enzyme-linked immunosorbent assay, and statistical analyses were performed using descriptive statistics, mean differences, 95% CIs, and P values (analysis of variance). Results: All growth factor preparation methods showed elevated concentrations of the growth factors VEGF, bFGF, PDGF-AB, and TGF-β1 compared with those of whole blood. Large interindividual differences were found in VEGF and bFGF concentrations. Respective values (mean ± SD in pg/mL) for whole blood, SmartPrep-2, PC, and PRP powder were as follows: VEGF (574 ± 147, 528 ± 233, 1087 ± 535, and 1722), bFGF (198 ± 164, 410 ± 259, 151 ± 99, and 542), PDGF-AB (2394 ± 451, 17,846 ± 3087, 18,461 ± 4455, and 23,023), and TGF-β1 (14,356 ± 4527, 77,533 ± 13,918, 68,582 ± 7388, and 87,495). IGF-1 was found in SmartPrep-2 (1539 ± 348 pg/mL). For PC (2266 ± 485 pg/mL), IGF-1 was measured at the same levels of whole blood (2317 ± 711 pg/mL) but was not detectable in PRP powder. IL-1α was detectable in whole blood (111 ± 35 pg/mL) and SmartPrep-2 (119 ± 44 pg/mL). Conclusion: Problems with PRP such as absent standardization, lack of consistency among studies, and black box dosage could be solved by using characterized PRP powder made by pooling and lyophilizing multiple PCs. The new PRP powder opens up new possibilities for PRP research as well as for the treatment of patients. Clinical Relevance: The preparation of pooled PRP by means of lyophilization may allow physicians to apply a defined amount of growth factors by using a defined amount of PRP powder. Moreover, PRP powder as a dry substance with no need for centrifugation could become ubiquitously available, thus saving time and staff resources in clinical practice. However, before transferring the results of this basic science study to clinical application, regulatory issues have to be cleared.


RSC Advances ◽  
2016 ◽  
Vol 6 (32) ◽  
pp. 26835-26855 ◽  
Author(s):  
Promita Bhattacharjee ◽  
Deboki Naskar ◽  
Tapas K. Maiti ◽  
Debasis Bhattacharya ◽  
Subhas C. Kundu

Nanofibrous PCL matrix with non-mulberry silk fibroin grafting and electrodeposited nHAp was used successfully as dual growth factor delivery medium for in vitro osteogenesis.


2021 ◽  
Vol 7 (3) ◽  
pp. 103-117
Author(s):  
Deepak Grover ◽  
Navneet Kaur ◽  
Gurpreet Kaur

With the advanced and improved knowledge of bone regeneration on the molecular level, some of key molecules that alter the complicated physiological method were identified, and are already in scientific use or beneath research to enhance bone restore. Of those molecules, BMPs were the maximum considerably studied, as they are robust osteoinductive elements. They result in the mitogenesis of mesenchymal stem cells (MSCs) and different osteoprogenitors, and their differentiation in the direction of osteoblasts. Other growth factors except BMPs which have been implicated through out the bone regeneration, with one-of-a-kind features with respect of cell proliferation, chemotaxis and angiogenesis, are also being investigated or are presently getting used to reinforce bone restore, which include platelet-derived growth factor, transforming growth factor- β, insulin-like growth factor-1, vascular endothelial growth factor and fibroblast growth factor, amongst others. One present day technique to enhance bone regeneration and soft-tissue recovery with the aid of using nearby application of growth factors is the use of platelet-rich plasma, an extent of the plasma fraction of autologous blood with platelet concentrations above baseline, that is wealthy in most of the aforementioned molecules. This overview focuses and target on the biological mediators that regulates key cellular events which have a capacity to induce the method of tissue repair and regeneration.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Roberto Alfonso Guzman ◽  
Masahiro Maruyama ◽  
Seyedsina Moeinzadeh ◽  
Elaine Lui ◽  
Ning Zhang ◽  
...  

Abstract Background Approximately one third of patients undergoing core decompression (CD) for early-stage osteonecrosis of the femoral head (ONFH) experience progression of the disease, and subsequently require total hip arthroplasty (THA). Thus, identifying adjunctive treatments to optimize bone regeneration during CD is an unmet clinical need. Platelet-derived growth factor (PDGF)-BB plays a central role in cell growth and differentiation. The aim of this study was to characterize mesenchymal stromal cells (MSCs) that were genetically modified to overexpress PDGF-BB (PDGF-BB-MSCs) in vitro and evaluate their therapeutic effect when injected into the bone tunnel at the time of CD in an in vivo rabbit model of steroid-associated ONFH. Methods In vitro studies: Rabbit MSCs were transduced with a lentivirus vector carrying the human PDGF-BB gene under the control of either the cytomegalovirus (CMV) or phosphoglycerate (PGK) promoter. The proliferative rate, PDGF-BB expression level, and osteogenic differentiation capacity of unmodified MSCs, CMV-PDGF-BB-MSCs, and PGK-PDGF-BB-MSCs were assessed. In vivo studies: Twenty-four male New Zealand white rabbits received an intramuscular (IM) injection of methylprednisolone 20 mg/kg. Four weeks later, the rabbits were divided into four groups: the CD group, the hydrogel [HG, (a collagen-alginate mixture)] group, the MSC group, and the PGK-PDGF-BB-MSC group. Eight weeks later, the rabbits were sacrificed, their femurs were harvested, and microCT, mechanical testing, and histological analyses were performed. Results In vitro studies: PGK-PDGF-BB-MSCs proliferated more rapidly than unmodified MSCs (P < 0.001) and CMV-PDGF-BB-MSCs (P < 0.05) at days 3 and 7. CMV-PDGF-BB-MSCs demonstrated greater PDGF-BB expression than PGK-PDGF-BB-MSCs (P < 0.01). However, PGK-PDGF-BB-MSCs exhibited greater alkaline phosphatase staining at 14 days (P < 0.01), and osteogenic differentiation at 28 days (P = 0.07) than CMV-PDGF-BB-MSCs. In vivo: The PGK-PDGF-BB-MSC group had a trend towards greater bone mineral density (BMD) than the CD group (P = 0.074). The PGK-PDGF-BB-MSC group demonstrated significantly lower numbers of empty lacunae (P < 0.001), greater osteoclast density (P < 0.01), and greater angiogenesis (P < 0.01) than the other treatment groups. Conclusion The use of PGK-PDGF-BB-MSCs as an adjunctive treatment with CD may reduce progression of osteonecrosis and enhance bone regeneration and angiogenesis in the treatment of early-stage ONFH.


2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Isaac A. Rodriguez ◽  
Emily A. Growney Kalaf ◽  
Gary L. Bowlin ◽  
Scott A. Sell

Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP). PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in bothin vitroandin vivoscenarios, to date its use and delivery have not been optimized for bone regeneration. Issues remain with the effective delivery of the platelet-derived growth factors to a localized site of injury, the activation and temporal release of the growth factors, and the rate of growth factor clearance. This review will briefly describe the physiological principles behind PRP use and then discuss how engineering its method of delivery may ultimately impact its ability to successfully translate to widespread clinical use.


2018 ◽  
Vol 19 (12) ◽  
pp. 3750 ◽  
Author(s):  
Kurt Ballmer-Hofer

Judah Folkman’s landmark discovery in the 1970s showing that tumors, growing beyond a few millimeters in diameter, depend on de novo vascularization triggered by specific growth factors released by tumor cells encountering hypoxia [...]


2015 ◽  
Vol 1088 ◽  
pp. 500-502 ◽  
Author(s):  
Li Ming Yang ◽  
Zhen Zhe Liu ◽  
Shu Ping Chen ◽  
Chun Xie ◽  
Bin Wu

Objective: To study the effect of concentrated growth factor (CGF) on reducing bone resorption in immediate implant. Methods: 20 immediate implant patients were divided into two groups, each group included 10 patients who were treated by adding CGF or Bio-oss to the gap of implant-bone, respectively; the labial new bone regeneration was evaluated in postoperative 1 years using cone beam CT. Results: The buccal bone width variation of the CGF group was 0.85±0.25mm, and the Bio-oss group was 0.35±0.25mm (p <0.05). Conclusion: The CGF has no significant role in promoting new bone regeneration when was used alone in the gap of implant - bone in immediate implant


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