scholarly journals The Treatment of Acute Diaphyseal Long-bones Fractures with Orthobiologics and Pharmacological Interventions for Bone Healing Enhancement: A Systematic Review of Clinical Evidence

2020 ◽  
Vol 7 (1) ◽  
pp. 22
Author(s):  
Giuseppe Marongiu ◽  
Andrea Contini ◽  
Andrea Cozzi Lepri ◽  
Matthew Donadu ◽  
Marco Verona ◽  
...  
Keyword(s):  
Systematic Review ◽  
Growth Factors ◽  
Bone Healing ◽  
Healing Process ◽  
Bone Matrix ◽  
Femoral Fractures ◽  
Current Evidence ◽  
Long Bones ◽  
Cell Therapies ◽  
Diaphyseal Fractures

Background: The healing of long bones diaphyseal fractures can be often impaired and eventually end into delayed union and non-union. A number of therapeutic strategies have been proposed in combination with surgical treatment in order to enhance the healing process, such as scaffolds, growth factors, cell therapies and systemic pharmacological treatments. Our aim was to investigate the current evidence of bone healing enhancement of acute long bone diaphyseal fractures. Methods: A systematic review was conducted by using Pubmed/MEDLINE; Embase and Ovid databases. The combination of the search terms “long-bones; diaphyseal fracture; bone healing; growth factors; cell therapies; scaffolds; graft; bone substitutes; orthobiologics; teriparatide”. Results: The initial search resulted in 4156 articles of which 37 papers fulfilled the inclusion criteria and were the subject of this review. The studies included 1350 patients (837 males and 513 females) with a mean age of 65.3 years old. Conclusions: General lack of high-quality studies exists on the use of adjuvant strategies for bone healing enhancement in acute shaft fractures. Strong evidence supports the use of bone grafts, while only moderate evidence demineralized bone matrix and synthetic ceramics. Conflicting results partially supported the use of growth factors and cell therapies in acute fractures. Teriparatide showed promising results, particularly for atypical femoral fractures and periprosthetic femoral fractures.

scholarly journals Bone Marrow-Derived Cell Therapies to Heal Long-Bone Nonunions: A Systematic Review and Meta-Analysis—Which Is the Best Available Treatment?

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Silvia Palombella ◽  
Silvia Lopa ◽  
Silvia Gianola ◽  
Luigi Zagra ◽  
Matteo Moretti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Healing ◽  
Healing Rate ◽  
Meta Analysis ◽  
Long Bone ◽  
Current Evidence ◽  
Positive Trend ◽  
Case Control Studies ◽  
Cell Therapies

Nonunions represent one of the major indications for clinical settings with stem cell-based therapies. The objective of this research was to systematically assess the current evidence for the efficacy of bone marrow-derived cell-based approaches associated or not with bone scaffolds for the treatment of nonunions. We searched MEDLINE (PubMed) and CENTRAL up to July 2019 for clinical studies focused on the use of cell-based therapies and bone marrow derivatives to treat bone nonunions. Three investigators independently extracted the data and appraised the risk of bias. We analysed 27 studies including a total number of 347 participants exposed to four interventions: bone marrow concentrate (BMAC), BMAC combined with scaffold (BMAC/Scaffold), bone marrow-derived mesenchymal stromal cells (BMSCs), and BMSC combined with scaffold (BMSC/Scaffold). Two controlled studies showed a positive trend in bone healing in favour of BMAC/Scaffold or BMSC/Scaffold treatment against bone autograft, although the difference was not statistically significant (RR 0.11, 95% CI -0.05; 0.28). Among single cohort studies, the highest mean pooled proportion of healing rate was reported for BMAC (77%; 95% CI 63%-89%; 107 cases, n=8) and BMAC/Scaffold treatments with (71%; 95% CI 50%-89%; 117 cases, n=8) at 6 months of follow-up. At 12 months of follow-up, an increasing proportion of bone healing was observed in all the treatment groups, ranging from 81% to 100%. These results indicate that BMAC or BMAC/Scaffold might be considered as the primary choice to treat nonunions with a successful healing rate at a midterm follow-up. Moreover, this meta-analysis highlighted that the presence of a scaffold positively influences the healing rate at a long-term follow-up. More case-control studies are still needed to support the clinical improvement of cell-based therapies against autografts, up to now considered as the gold standard for the treatment of nonunions.

Osteogenic Potency of Secretome Bone Marrow Derived Mesenchymal Stem Cells: A Literature Review

2018 ◽  
Vol 24 (8) ◽  
pp. 6206-6208
Author(s):  
Ismail Hadisoebroto Dilogo ◽  
Jessica Fiolin ◽  
Petrus Aprianto
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Bone Healing ◽  
Mechanical Stability ◽  
Healing Process ◽  
Study Groups ◽  
Non Union ◽  
Acute Kidney Disease ◽  
Diamond Concept

Treatment of non-union bone healing has been an unsolved problem in Orthopaedic surgery despite many advances. The most commonly adapted concept is the diamond concept including the osteoprogenitor cells, osteoinductive proteins, osteoconductive scaffolds and mechanical stability. Recent study groups worldwide have been studying the Mesenchymal Stem Cells as an adjunct to increase the bone healing process. However, newer literatures have shown that only few number of MSC transplanted will integrate. This paracrine mechanism is mediated by active secretion of cytokines, growth factors and enzymes called the secretome which is produced as a byproduct during the process of MSC culture. The addition of secretome itself alone is predicted to have the similar effect as the transplantation of MSC with less cost needed, and easier to obtain. The effect of MSC secretome has shown positive result on neurodegenerative disease, acute kidney disease, and cancer; but the effect on bone regeneration itself has never been studied. The MSC secretome have been proven to contain various cytokines (TGβ, some interleukins, GCSF, and many other cytokines) and growth factors (VEGF, EGF, PDGF, IGF-1, IGF-II, PLGF, HGF, NGF, BDNF). We also suspect the osteoinductive profile of MSC secretome due to the existence of BMP-2 which can be analysed using the ELISA spectrophotometry. The osteoinductive profile of secretome MSC will be able to replace the need of recombinant human BMP-2 (rhBMP-2) transplantation in treating bone defect and diminish the risk of excessive inflammation created by BMP-2 and also the carcinogenic potency.

scholarly journals Investigation of Peri-Implant Bone Healing Using Autologous Plasma Rich in Growth Factors in the Canine Mandible After 12 Weeks: A Pilot Study

2011 ◽  
Vol 5 (1) ◽  
pp. 168-173 ◽  
Author(s):  
Reza Birang ◽  
Mohammad Tavakoli ◽  
Mohammad Shahabouei ◽  
Alireza Torabi ◽  
Ali Dargahi ◽  
...  
Keyword(s):  
Growth Factors ◽  
Bone Healing ◽  
Healing Process ◽  
Optical Microscope ◽  
Autologous Plasma ◽  
Trabecular Thickness ◽  
Mixed Breed ◽  
Bone To Implant Contact ◽  
Bone Healing Process ◽  
Surrounding Bone

Introduction: Faster reconstruction of patients’ masticatory systems is the aim of modern dentistry. A number of studies have indicated that application of growth factors to the surface of a dental implant leads to accelerated and enhanced osseointegration. The objective of the present study was to investigate the effect of plasma rich in growth factors on peri-implant bone healing. Materials and Methods: For the purpose of this study, two healthy, mixed-breed canines were selected, and the premolars were extracted from both sides of the mandible. Three months after premolar removal, 12 implants, each 5 mm in diameter and 10 mm in length, were placed in osteotomy sites on both sides of the mandible. Prior to placement, plasma rich in growth factors was applied to the surfaces of six implants, while the other six were used without plasma rich in growth factors. The implants were removed after 12 weeks along with the bone surrounding the sites using a trephine bur. One mesiodistal section containing the surrounding bone from each implant block, 50 µm in diameter, was prepared for histologic and histomorphometric investigation with an optical microscope. Results: The sites with implants treated with plasma rich in growth factors showed more bone-to-implant contact compared to control sites. Also, higher values for bone trabecular thickness and bone maturity were recorded for the PRGF-treated sites than for the control sites. Conclusion: Application of plasma rich in growth factors to the surface of an implant may enhance the bone healing process as well as bone-to-implant contact, thereby helping to achieve faster osseointegration.

scholarly journals The biology and treatment of acute long-bones diaphyseal fractures: Overview of the current options for bone healing enhancement

Bone Reports ◽  
2020 ◽  
Vol 12 ◽  
pp. 100249 ◽  
Author(s):  
Giuseppe Marongiu ◽  
Andrea Dolci ◽  
Marco Verona ◽  
Antonio Capone
Keyword(s):  
Bone Healing ◽  
Long Bones ◽  
Diaphyseal Fractures

scholarly journals Electromagnetic stimulation as coadjuvant in the healing of diaphyseal femoral fractures: a randomized controlled trial

2014 ◽  
pp. 67-71 ◽  
Author(s):  
Alfredo Martinez Rondanelli ◽  
Juan Pablo Martinez ◽  
María Elena Moncada ◽  
Eliana Manzi ◽  
Carlos Rafael Pinedo ◽  
...  
Keyword(s):  
Electromagnetic Field ◽  
Bone Healing ◽  
Controlled Trial ◽  
Weight Bearing ◽  
Femoral Fractures ◽  
Femoral Diaphysis ◽  
Randomized Controlled ◽  
Electromagnetic Stimulation ◽  
Diaphyseal Fractures ◽  
The Mean

Introduction: There is controversy in medical literature regarding the use of electromagnetic fields to promote bone healing. Methods: After designing and building devices capable of generating an electromagnetic field for this study, their safety was confirmed and the electromagnetic therapy was randomly allocated and compared to placebo in patients with fracture of the femoral diaphysis. Treatment began six weeks after the fracture and it was administered once a day, during 1 h, for eight consecutive weeks. Twenty devices were built, 10 of which were placebo-devices. Between June 2008 and October 2009, 64 patients were randomized in two different hospitals and were followed for 24 weeks. The mean age was 30 years (18-59) and 81% were males. Results: Healing observed at week 12 was 75% vs. 58% (p= 0.1); at week 18, it was 94% vs. 80% (p= 0.15); and at week 24, it was 94% vs. 87% (p= 0.43) for the device group and the placebo group, respectively. Discussion: This study suggests that an electromagnetic field stimulus can promote earlier bone healing compared to placebo in femoral diaphyseal fractures. Faster bone healing translates into sooner weight bearing, which – in turn – permits quicker return to normal daily activities.

scholarly journals Accelerating the Bone Healing Process by the Intervention of the Platelet Growth Factors Impregnated in Collagen. An experimental and theoretical mathematical model

2019 ◽  
Vol 56 (4) ◽  
pp. 973-979
Author(s):  
Sidonia Susanu ◽  
Mara Popescu ◽  
Bogdan Caba ◽  
Petru Plamadeala ◽  
Andreea Moraru ◽  
...  
Keyword(s):  
Field Theory ◽  
Mathematical Model ◽  
Growth Factors ◽  
Symmetry Breaking ◽  
Bone Healing ◽  
Healing Process ◽  
Collagen Sponge ◽  
Morphogenetic Protein ◽  
Breaking Mechanism ◽  
Bone Healing Process

A bone defect with standard dimensions and localization is produced. Inside this defect a polymer (collagen sponge) impregnated with growing factors, i. e. bone morphogenetic protein - BMP, is introduced. For the witness lot, the same defect is produced, in which the same polymer is introduced, but without any growing factors. It is found that the growing factor not only remains at the initial site, but also has effect on the bone regeneration process. A mathematical model is constructed using a field theory of multifractal type based on the spontaneous symmetry breaking mechanism to exploit such dynamics in biostructures. This mechanism contains all the informational �ingredients�: the multivalent logic based multifractal bit, the algorithm based networks through spatial cnoidal modes of oscilation, etc. In such context, the evolution of all biostructures, through a mechanism that mimics a 3D biological printer, can become operational.

scholarly journals Macrophage Polarization and Alveolar Bone Healing Outcome: Despite a Significant M2 Polarizing Effect, VIP and PACAP Treatments Present a Minor Impact in Alveolar Bone Healing in Homeostatic Conditions

2021 ◽  
Vol 12 ◽  
Author(s):  
Michelle de Campos Soriani Azevedo ◽  
Angélica Cristina Fonseca ◽  
Priscila Maria Colavite ◽  
Jéssica Lima Melchiades ◽  
André Petenuci Tabanez ◽  
...  
Keyword(s):  
Bone Healing ◽  
Host Response ◽  
Alveolar Bone ◽  
Macrophage Polarization ◽  
Healing Process ◽  
Bone Matrix ◽  
Essential Element ◽  
Trabecular Thickness ◽  
Bone Healing Process

Host inflammatory immune response comprises an essential element of the bone healing process, where M2 polarization allegedly contributes to a favorable healing outcome. In this context, immunoregulatory molecules that modulate host response, including macrophage polarization, are considered potential targets for improving bone healing. This study aims to evaluate the role of the immunoregulatory molecules VIP (Vasoactive intestinal peptide) and PACAP (Pituitary adenylate cyclase activating polypeptide), which was previously described to favor the development of the M2 phenotype, in the process of alveolar bone healing in C57Bl/6 (WT) mice. Experimental groups were submitted to tooth extraction and maintained under control conditions or treated with VIP or PACAP were evaluated by microtomographic (µCT), histomorphometric, immunohistochemical, and molecular analysis at 0, 3, 7, and 14 days to quantify tissue healing and host response indicators at the healing site. Gene expression analysis demonstrates the effectiveness of VIP or PACAP in modulating host response, evidenced by the early dominance of an M2-type response, which was paralleled by a significant increase in M2 (CD206+) in treated groups. However, despite the marked effect of M1/M2 balance in the healing sites, the histomorphometric analysis does not reveal an equivalent/corresponding modulation of the healing process. µCT reveals a slight increase in bone matrix volume and the trabecular thickness number in the PACAP group, while histomorphometric analyzes reveal a slight increase in the VIP group, both at a 14-d time-point; despite the increased expression of osteogenic factors, osteoblastic differentiation, activity, and maturation markers in both VIP and PACAP groups. Interestingly, a lower number of VIP and PACAP immunolabeled cells were observed in the treated groups, suggesting a reduction in endogenous production. In conclusion, while both VIP and PACAP treatments presented a significant immunomodulatory effect with potential for increased healing, no major changes were observed in bone healing outcome, suggesting that the signals required for bone healing under homeostatic conditions are already optimal, and additional signals do not improve an already optimal process. Further studies are required to elucidate the role of macrophage polarization in the bone healing process.

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