Bone Healing Process Research Articles

Suitability of Chitosan Scaffolds with Carbon Nanotubes for Bone Defects Treated with Photobiomodulation.

Biomaterials have been investigated as an alternative for the treatment of bone defects, such as chitosan/carbon nanotubes scaffolds, which allow cell proliferation. However, bone regeneration can be accelerated by electrotherapeutic resources that act on bone metabolism, such as low-level laser therapy (LLLT). Thus, this study evaluated the regeneration of bone lesions grafted with chitosan/carbon nanotubes scaffolds and associated with LLLT. For this, a defect (3 mm) was created in the femur of thirty rats, which were divided into 6 groups: Control (G1/Control), LLLT (G2/Laser), Chitosan/Carbon Nanotubes (G3/C+CNTs), Chitosan/Carbon Nanotubes with LLLT (G4/C+CNTs+L), Mineralized Chitosan/Carbon Nanotubes (G5/C+CNTsM) and Mineralized Chitosan/Carbon Nanotubes with LLLT (G6/C+CNTsM+L). After 5 weeks, the biocompatibility of the chitosan/carbon nanotubes scaffolds was observed, with the absence of inflammatory infiltrates and fibrotic tissue. Bone neoformation was denser, thicker and voluminous in G6/C+CNTsM+L. Histomorphometric analyses showed that the relative percentage and standard deviations (mean ± SD) of new bone formation in groups G1 to G6 were 59.93 ± 3.04a (G1/Control), 70.83 ± 1.21b (G2/Laser), 70.09 ± 4.31b (G3/C+CNTs), 81.6 ± 5.74c (G4/C+CNTs+L), 81.4 ± 4.57c (G5/C+CNTsM) and 91.3 ± 4.81d (G6/C+CNTsM+L), respectively, with G6 showing a significant difference in relation to the other groups (a ≠ b ≠ c ≠ d; p < 0.05). Immunohistochemistry also revealed good expression of osteocalcin (OC), osteopontin (OP) and vascular endothelial growth factor (VEGF). It was concluded that chitosan-based carbon nanotube materials combined with LLLT effectively stimulated the bone healing process.

The Effect of Diclofenac Sodium on Callus Formation in White Male Rat (Rattus norvegicus) Cruris Fracture Healing

Highlights: Sodium diclofenac is one of NSAID a common treatment to relieve pain associated with bone fractures. Sodium diclofenac with a some dose of body weight could decrease the callus quality on fracture healing. Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac sodium, are standard treatments to relieve pain associated with bone fractures. The bone healing process consists of four stages: inflammation, soft callus formation, complex callus formation, and bone remodeling. Previous studies mentioned that intake of NSAIDs (sodium diclofenac) could inhibit the bone healing process. This study examined the effect of diclofenac sodium intake on callus formation in fracture healing. In this study, thirty-six rats (Rattus Norvegicus) with fractures were used and divided into two groups, namely 18 rats for the control and 18 rats for the treatment group. In the treatment group, each rat was given 1.8 mg sodium diclofenac/150 grams of body weight per day. In the control group, each rat was given CMC-Na 0.5% with equal volume as diclofenac sodium in the treatment group. After 28 days, all the rats were stunned until dead, and the diameter and strength of their calluses were measured. In the treatment group with diclofenac sodium1.8 mg/ 150 grams BW/ 28 days after the tibia bone callus was pressed using the Shimadzu tool, the lowest callus strength was found to be 56.500 N, and the highest callus strength was 59.000 N. The lowest callus diameter in the treatment group was 4 mm, the highest was 5 mm. In the control group, the lowest callus strength was 76 N, and the highest callus strength was 77 N. The lowest callus diameter in the control group was 6 mm, and the highest was 8 mm. The strongest callus in the treatment group was found in the sixth observation, with a value of 59 N and a diameter of 4 mm. In the control group, the highest callus strength was 77 N, with a diameter of 7-8 mm. These measurements were found on the 5th, 7th, 8th, 9th, 16th, and 17th observations. Diclofenac sodium with a dose of 1.8 mg/150 grams of body weight could decrease the callus quality parameters, such as callus strength and diameter on fracture healing.

Nonlinear micro finite element models based on digital volume correlation measurements predict early microdamage in newly formed bone

Bone regeneration in critical-sized defects is a clinical challenge, with biomaterials under constant development aiming at enhancing the natural bone healing process. The delivery of bone morphogenetic proteins (BMPs) in appropriate carriers represents a promising strategy for bone defect treatment but optimisation of the spatial-temporal release is still needed for the regeneration of bone with biological, structural, and mechanical properties comparable to the native tissue. Nonlinear micro finite element (μFE) models can address some of these challenges by providing a tool able to predict the biomechanical strength and microdamage onset in newly formed bone when subjected to physiological or supraphysiological loads. Yet, these models need to be validated against experimental data. In this study, experimental local displacements in newly formed bone induced by osteoinductive biomaterials subjected to in situ X-ray computed tomography compression in the apparent elastic regime and measured using digital volume correlation (DVC) were used to validate μFE models. Displacement predictions from homogeneous linear μFE models were highly correlated to DVC-measured local displacements, while tissue heterogeneity capturing mineralisation differences showed negligible effects. Nonlinear μFE models improved the correlation and showed that tissue microdamage occurs at low apparent strains. Microdamage seemed to occur next to large cavities or in biomaterial-induced thin trabeculae, independent of the mineralisation. While localisation of plastic strain accumulation was similar, the amount of damage accumulated in these locations was slightly higher when including material heterogeneity. These results demonstrate the ability of the nonlinear μFE model to capture local microdamage in newly formed bone tissue and can be exploited to improve the current understanding of healing bone and mechanical competence. This will ultimately aid the development of BMPs delivery systems for bone defect treatment able to regenerate bone with optimal biological, mechanical, and structural properties.

The Effect of Platelet-Rich Plasma on Type I Collagen Production, VEGF Expression, and Neovascularization after Femoral Bone Implants: A Study on Rat Models.

IntroductionPlatelet-rich plasma (PRP) contains many growth factors, such as FGF, which induces the production of type I collagen, and VEGF, which induces neovascularization, all of which are important in bone healing. This study aimed to evaluate the effect of PRP administration on type I collagen production, VEGF expression, and neovascularization in rat models following femoral bone implants using K-wire.MethodsAn experimental randomized control study was conducted on 24 white male rats (Rattus norvegicus) in the Wistar strain that underwent K-wire implantation, where PRP was administered to the treatment groups. The amount of type I collagen was measured by immunohistochemistry VEGF expression using sandwich ELISA, and neovascularization by histopathological examination.ResultsThe amount of type I collagen in the treatment group (50–>150/field of view) was significantly higher than the control group (0–99/field of view; p=0.003). VEGF expression in the treatment groups was significantly higher than controls: 10.90±4.47 and 2.29±0.92, respectively (p=0.006). Mean number of new vessels formed on fibrotic capsules in the treatment groups was significantly (p=0.007) higher than the control groups (2.69±1.03 vs 0.67±0.52).ConclusionThe use of PRP significantly increased type I collagen production, VEGF expression, and neovascularization in rat models, elucidating the potential of PRP to be used in clinical settings to enhance the bone-healing process.

ALX1-transcribed LncRNA AC132217.4 promotes osteogenesis and bone healing via IGF-AKT signaling in mesenchymal stem cells.

The osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) is critical for bone formation and regeneration. A high non-/delayed-union rate of fracture healing still occurs in specific populations, implying an urgent need to discover novel targets for promoting osteogenesis and bone regeneration. Long non-coding (lnc)RNAs are emerging regulators of multiple physiological processes, including osteogenesis. Based on differential expression analysis of RNA sequencing data, we found that lncRNA AC132217.4, a 3'UTR-overlapping lncRNA of insulin growth factor 2 (IGF2), was highly induced during osteogenic differentiation of BMSCs. Afterward, both gain-of-function and loss-of-function experiments proved that AC132217.4 promotes osteoblast development from BMSCs. As for its molecular mechanism, we found that AC132217.4 binds with IGF2 mRNA to regulate its expression and downstream AKT activation to control osteoblast maturation and function. Furthermore, we identified two splicing factors, splicing component 35 KDa (SC35) and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), which regulate the biogenesis of AC132217.4 at the post-transcriptional level. We also identified a transcription factor, ALX1, which regulates AC132217.7 expression at the transcriptional level to promote osteogenesis. Importantly, in-vivo over-expression of AC132217.4 essentially promotes the bone healing process in a murine tibial drill-hole model. Our study demonstrates that lncRNA AC132217.4 is a novel anabolic regulator of BMSC osteogenesis and could be a plausible therapeutic target for improving bone regeneration.

Investigation of the process intergrowth of bone tissue into the hole in titanium implants (Experimental research)

IntroductionDespite the use of modern implants, complications such as nonunion and avascular necrosis of the femoral head are observed in femoral neck fractures (FNF). We have created a new perforated I-beam implant for FNF osteosynthesis and developed a new osteosynthesis philosophy based not only on the mechanical and biomechanical interaction of the bone-implant system, but also on the interaction of the biological properties of the bone and the implant.The purpose of the work is to study the interaction of the biological process of the bone - its regeneration (germination) of bone tissue into the holes of the implant. Materials and methodsThe experiment was carried out on fourteen Chinchilla rabbits in accordance with all international standards. A perforated implant specially made of titanium (ChM, Poland) was surgically implanted into the proximal femur.The implant measurements were as follows: length – 6 mm, width – 3 mm, thickness – 2 mm, 2 holes with a diameter of 2 mm. The 14 rabbits were divided into 7 groups. After 1, 2, 3, 4, 5, 10 and 12 weeks the animals were withdrawn from the experiment according to the standard rules in sequential order. The preparations were placed in a formalin solution and sent to the pathomorphology laboratory (CITO, Russia) for histological studies. ResultsWeekly histopathological studies revealed a gradual transition from the organization of a hematoma to the formation of mature bone tissue in the holes of the implants. The titanium implant is bioinert and did not cause any visible reactions from the bone tissue. Simultaneous integration of vascular proliferation and newly formed bone tissue into the implant holes were revealed. On 10–12-week preparations, the formation of trabecular structures of mature bone tissue was revealed in the holes of the implants and elements of adipose and bone marrow tissue were observed. Macroscopic examination of 4–5-week preparations showed almost complete filling of the holes with bone tissue. On 10–12-week preparations, the bone tissue in the holes of the implants did not differ from the bone tissue surrounding the implant. The processes of formation of mature bone tissue in the holes of the implants were similar to the processes of physiological bone healing (regeneration) at the fracture site. ConclusionsThe obtained results show the following: 1.The titanium implant is bioinert and does not cause any visible reactions from the bone tissue; 2. There is a gradual process of formation of new vessels, and then the formation of new bone tissue in the holes of the implant instead of the one damaged during implantation.Thus, the results of this experiment indirectly confirm our assumption that a perforated implant for FNF osteosynthesis will participate not only in the mechanical and biomechanical interaction of the bone-implant system, but will also include the 3rd element in this system - the biological properties of the bone itself. We assume that these properties of the new implant will increase blood flow in the femoral neck and partially replenish the volume of bone tissue destroyed during osteosynthesis which does not occur with FNF osteosynthesis by any of the known implants.

Patient‐Specific Self‐Powered Metamaterial Implants for Detecting Bone Healing Progress

AbstractThere is an unmet need for developing a new class of smart medical implants with novel properties and advanced functionalities. Here, the concept of “self‐aware implants” is proposed to enable the creation of a new generation of multifunctional metamaterial implantable devices capable of responding to their environment, empowering themselves, and self‐monitoring their condition. These functionalities are achieved via integrating nano energy harvesting and mechanical metamaterial design paradigms. Various aspects of the proposed concept are highlighted by developing proof‐of‐concept interbody spinal fusion cage implants with self‐sensing, self‐powering, and mechanical tunability features. Bench‐top testing is performed using synthetic biomimetic and human cadaver spine models to evaluate the electrical and mechanical performance of the developed patient‐specific metamaterial implants. The results show that the self‐aware cage implants can diagnose bone healing process using the voltage signals generated internally through their built‐in contact‐electrification mechanisms. The voltage and current generated by the implants under the axial compression forces of the spine models reach 9.2 V and 4.9 nA, respectively. The metamaterial implants can serve as triboelectric nanogenerators to empower low‐power electronics. The capacity of the proposed technology to revolutionize the landscape of implantable devices and to achieve better surgical outcomes is further discussed.

The Osteoinductivity of Calcium Phosphate-Based Biomaterials: A Tight Interaction With Bone Healing.

Calcium phosphate (CaP)-based bioceramics are the most widely used synthetic biomaterials for reconstructing damaged bone. Accompanied by bone healing process, implanted materials are gradually degraded while bone ultimately returns to its original geometry and function. In this progress report, we reviewed the complex and tight relationship between the bone healing response and CaP-based biomaterials, with the emphasis on the in vivo degradation mechanisms of such material and their osteoinductive properties mediated by immune responses, osteoclastogenesis and osteoblasts. A deep understanding of the interaction between biological healing process and biomaterials will optimize the design of CaP-based biomaterials, and further translate into effective strategies for biomaterials customization.

Effectiveness of Photobiomodulation Therapy on Human Bone Healing in Dentistry: A Systematic Review.

Background: Despite the association, possible causality, and contradictory results, numerous studies evaluate photobiomodulation (PBM) therapy on the process of human bone healing. It is of paramount importance to review the available literature to elucidate the effect of laser on the bone healing process in dentistry. Objective: This systematic review analyzes the effectiveness of PBM therapy to improve bone healing in dentistry. Methods: A systematic search of studies published up to September 2021 and listed in PubMed, Cochrane Library, and Embase databases and registered on PROSPERO (CRD42020212790). Twenty-five studies were selected. Results: The most used device was diode laser. PBM therapy parameters varied greatly. From the 25 selected studies, 17 had the primary outcome bone healing. Of these, 11 studies revealed improvement in bone healing with PBM therapy and six studies suggested no effect. The other eight studies evaluated secondary parameters. In seven studies, some of the clinical parameters were improved with the PBM therapy. Conclusions: Within the limitations of this systematic review, bone healing in dentistry was improved with the use of PBM. PBM therapy can promote anti-inflammatory and analgesic effects, improve healing, as well as enhance quality of life related to oral health. Within the areas analyzed in dentistry, laser parameters varied greatly, becoming difficult to consider a definite protocol as a proper one.

The Roles of Insulin Growth Factors-1 (IGF-1) in Bone Graft to increase Osteogenesis

Background: Bone graft material is used with periodontal flap procedure that is expected to help the growth of new bone through the process of osteogenesis, osteoinduction, and osteoconduction. Some work must be done to support the regeneration of periodontal tissue, including the three key elements of principal, such as scaffolds (collagen and bone material), signal molecules (growth factors) and cells. IGF-1 is a growth factor that has been studied to stimulate the replication of osteoblasts and bone matrix synthesis of bone remodeling process. Osteocalcin is a specific product of osteoblasts, in a previous study that the increase of osteocalcin indicates an increase in bone formation markers. Osteopontin expression by kondrosit showed the role of these cell in sintesizing matrix that have a main role for osteoclast resorpsion dan bone remodeling. Objective: To know the effect of IGF-1 on bone healing process that has been applied xenograft with attention to osteoblast, osteoclast, osteopontin and osteocalcin expression in animal model. Methods: This study was an experimental study in the rabbit. Comparing two groups, xenograft + IGF-1 and others just xenograft, was applied to the tibia’s defect for 21 days. Results: There are significant differences between the groups. The expression of osteoblast, osteopontin and osteocalcin looks more numerous after 21 days on the xenograft + IGF-1 group than the group that only uses xenograft alone. Whereas expression of osteoclast was seen to be less in the xenograft + IGF-1 group. Conclusion: the use of IGF-1 as a fisiologic mediator in regenerate periodontal tissues proved to be effective with the increased expression of osteoblast, osteopontin, osteocalcin and decreased osteoclasts.

Novel Techniques and Future Perspective for Investigating Critical-Size Bone Defects.

A critical-size bone defect is a challenging clinical problem in which a gap between bone ends will not heal and will become a nonunion. The current treatment is to harvest and transplant an autologous bone graft to facilitate bone bridging. To develop less invasive but equally effective treatment options, one needs to first have a comprehensive understanding of the bone healing process. Therefore, it is imperative to leverage the most advanced technologies to elucidate the fundamental concepts of the bone healing process and develop innovative therapeutic strategies to bridge the nonunion gap. In this review, we first discuss the current animal models to study critical-size bone defects. Then, we focus on four novel analytic techniques and discuss their strengths and limitations. These four technologies are mass cytometry (CyTOF) for enhanced cellular analysis, imaging mass cytometry (IMC) for enhanced tissue special imaging, single-cell RNA sequencing (scRNA-seq) for detailed transcriptome analysis, and Luminex assays for comprehensive protein secretome analysis. With this new understanding of the healing of critical-size bone defects, novel methods of diagnosis and treatment will emerge.

Fabrication and characterization of PHEMA\u2013gelatin scaffold enriched with graphene oxide for bone tissue engineering

BackgroundGrowing investigations demonstrate that graphene oxide (GO) has an undeniable impact on repairing damaged bone tissue. Moreover, it has been stated in the literatures that poly(2-hydroxyethyl methacrylate) (PHEMA) and gelatin could provide a biocompatible structure.MethodsIn this research, we fabricated a scaffold using freeze-drying method comprised of PHEMA and gelatin, combined with GO. The validation of the successful fabrication of the scaffolds was performed utilizing Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction assay (XRD). The microstructure of the scaffolds was observed using scanning electron microscopy (SEM). The structural properties of the scaffolds including mechanical strength, hydrophilicity, electrical conductivity, and degradation rate were also evaluated. Human bone marrow‐derived mesenchymal stem cells (hBM-MSCs) were used to evaluate the cytotoxicity of the prepared scaffolds. The osteogenic potential of the GO-containing scaffolds was studied by measuring the alkaline phosphatase (ALP) activity after 7, 14, and 21 days cell culturing.ResultsSEM assay showed a porous interconnected scaffold with approximate pore size of 50–300 μm, appropriate for bone regeneration. The increase in GO concentration from 0.25 to 0.75% w/v exhibited a significant improvement in scaffolds compressive modulus from 9.03 ± 0.36 to 42.82 ± 1.63 MPa. Conventional four-probe analysis confirmed the electrical conductivity of the scaffolds in the semiconductor range. The degradation rate of the samples appeared to be in compliance with bone healing process. The scaffolds exhibited no cytotoxicity using MTT assay against hBM-MSCs. ALP analysis indicated that the PHEMA–Gel–GO scaffolds could efficiently cause the differentiation of hBM-MSCs into osteoblasts after 21 days, even without the addition of the osteogenic differentiation medium.ConclusionBased on the results of this research, it can be stated that the PHEMA–Gel–GO composition is a promising platform for bone tissue engineering.

High-purity magnesium screws modulate macrophage polarization during the tendon-bone healing process in the anterior cruciate ligament reconstruction rabbit model.

Magnesium (Mg) screws perform clinical potential in anterior cruciate ligament (ACL) reconstruction, and promote fibrocartilaginous entheses regeneration at the femoral entrance. We aim to prove that high-purity Magnesium (HP Mg) screws modulate macrophage polarization in fibrocartilage interface regeneration both in vitro and in vivo. HP Mg extracts performed good cytocompatibility and significantly promoted M2 macrophage polarization in the flow cytometry and ELISA assays. M2 macrophages stimulated fibrochondrocyte differentiation of co-cultured hBMSCs, and HP Mg extracts had synergistic effect on the process. Then we applied HP Mg screws, with Ti screws as control, in the ACL reconstruction rabbit model. In the histological and immunofluorescence analysis, HP Mg screws inhibited M1 polarization at 2 weeks and highly promoted M2 polarization at 2 and 4 weeks at the tendon–bone interface. Furthermore, regeneration of fibrocartilaginous entheses, rather than the fibrovascular scar interface, was detected in the HP Mg group at 12 weeks. For further mechanism study via RNA-seq detection and WB assays, we found that AKT1 was highly activated in M2 polarization, and HP Mg could stimulate AKT1 expression, rather than AKT2, in the early phase of tendon–bone healing. Our study elucidated macrophage polarization during tendon–bone healing process and emphasized HP Mg on M2 polarization and fibrocartilage interface regeneration via the selective activation of AKT1 and PI3K/AKT pathway.

Pathological differences in the bone healing processes between tooth extraction socket and femoral fracture

Despite various reports on the bone healing processes of tooth extraction socket and long bone fracture, the differences of pathological changes during these healing processes remain elusive. This study aims to elucidate the underlying mechanisms behind the pathophysiology of bone regeneration between the tooth extraction socket and femoral fractures through a comparative study. Eight-week-old male mice were used in the experiments. The maxillary first molar was extracted, and intramedullary nailing femoral fracture (semistabilized fracture repair) was performed in the femur. Pathological changes in these bone injuries were investigated by micro-CT, histology, immunohistochemistry, and RT-PCR until day 7 post operation. Pathological changes in drill hole injury created in cortical bone of femur were also examined. Micro-CT analyses revealed increases in mineralized tissues in both the tooth extraction socket and femoral fracture. Histological examinations revealed that tooth socket was repaired by intramembranous ossification, and intramedullary nailing femoral fracture was healed by endochondral ossification. Immunohistochemical investigation revealed that tooth socket healing associated with Sp7-positive cells but not Sox9, aggrecan, and type II collagen, while femoral fracture models exhibited positive signals for all antibodies. RT-PCR analyses revealed the expression of Sp7, Col1a1, and Col2a1 in tooth socket healing, and the expression of Sp7, Col1a1, Runx2, Sox9, Acan, Col2a1, and Col10a1 in intramedullary nailing femoral fracture. Drill hole injury was repaired primarily by intramembranous ossification when the periosteum was removed before making the hole. The present study demonstrated that the absence of cartilage appearance during tooth extraction socket healing indicates it as distinctly different pathological features from the healing processes of semistabilized femoral fracture. This study contributes to the understanding of the molecular and cellular characteristics of bone healing among the different sites of bone injury.

The Mixture Aqueous Extracts from Oxalis corniculata L. and Acmella caulirhiza Delile Accelerates Bone Healing in Fractured Rats

Background: Bone fracture is a condition in which there is a break in the continuity of the bone due to traumatic or pathological factors. Fracture management includes orthopedic, surgical, non-surgical techniques and drug treatments. However, these treatments possess a limitation. Facilitating bone healing process reduce the cost, the time of treatment and is also beneficial for a quick recovery of the patient. The present study aimed to investigate the effect of the mixture aqueous extracts from Oxalis corniculata and Acmella caulirhiza on the bone formation.&#x0D; Methodology: Wistar female rats were fractured using a drill machine by inserting a drill bit in the femur diaphysis. Fractured animals were subdivided into five groups. One group receiving palm oil, four groups receiving the mixture of plant extracts at the doses of 150, 300, 600 mg/kg or diclofenac at the dose of 357 mg/kg. Substances were given via percutaneous and oral routes for two weeks. At the end of the experimental period, bones were collected and homogenized for the evaluation of the following biochemical parameters: alkaline phosphatase (ALP); reduced glutathione (GSH), nitrites, superoxide dismutase (SOD), interleukin-1β and interleukin-6. Moreover, histomorphometry of the bone at the fracture site was realized.&#x0D; Results: Percutaneous treatment with the plant extracts resulted in a significant increase of ALP activity (p&lt;0.05) in fractured rats as compared to the control. The mixture extracts also alleviated the fracture-induced oxidative stress by increasing the concentrations of GSH and nitrites; SOD and catalase activities. Furthermore, the plant extracts improved deregulated cytokines observed in fractured bone. Histopathological examination showed a more pack-like structure with a significant decrease in trabeculae number, trabecular interspace with the increase in the bone thickness.&#x0D; Conclusion: The mixture aqueous extracts from Oxalis corniculata and Acmella caulirhiza possesses bone healing effect due to its ability to alleviate oxidative stress, regulate pro-inflammatory cytokines and improve the structure of the new bone formed.

FUNCTIONAL OUTCOME OF PRE-CONTOURED MEDIAL LOCKING COMPRESSION PLATE USING MIPO (MINIMaAL INVASIVEPLATING OSTEOSYNTHESIS) TECHNIQUE IN TREATMENT OF DISTAL TIBIAL FRACTURES

Introduction:- The management of distal tibial fractures remains challenging due to subcutaneous location of larger portion of tibia,paucity of soft tissue coverage and precarious blood supply of distal leg.Conservative management may be complicated by loss of reduction and subsequent malunion. MIPO (Minimal invasive plating osteosynthesis) has evolved as a newer concept to treat distal tibial fractures. It works on Biological fixation principle which assists physiological process of bone healing wisely with minimal operative intervention. Methods:- Prospective follow up study carried out at J.L.N. Medical College Ajmer from 1 Jan 2017 to 30 June 2018. 30 patients with distal tibial fractures were included and operated with pre-contoured medial locking compression plate using MIPO technique. Fractures were classified as per AO system and patients were followed and scored according to TEENY and WISS scoring criteria. Results:- Functional results according to TEENY and WISS scoring criteria was found excellent in 9 (30%), good in 16(53.33%), Fair in 3(10%) and poor in 2 (6.66%) patients. Poor outcome occurs due to development of complications Conclusion:-Internal fixation of distal tibial fractures with pre-contoured medial locking compression plate using MIPO technique is effective and safe and provides more stable construct with anatomical reduction.

Sequential Delivery of Different MicroRNA Nanocarriers Facilitates the M1-to-M2 Transition of Macrophages.

The early-stage repair of bone injuries dominated by the inflammatory phase is significant for successful bone healing, and the phenotypic transition of macrophages in the inflammatory phase plays indispensable roles during the bone healing process. The goal of this paper is to design a microRNA delivery nanocarrier for strictly temporal guidance of the polarization of macrophages by the sequential delivery of different microRNAs. The results showed that microRNA nanocarriers, synthesized through free radical polymerization, could be internalized by macrophages with about a cellular uptake efficiency of 80%, and the sequential delivery of microRNA-155 nanocarriers and microRNA-21 nanocarriers proved, for the first time, that it could promote an efficient and timely switch from the M1 to the M2 phenotype along the time point of bone tissue repair. The strategy proposed in this paper holds potential for controlling sequential M1-to-M2 polarization of macrophages, which provides another perspective for the treatment of bone tissue regeneration.

PERIODONTAL STATUS IN PATIENTS WITH MANDIBULAR FRACTURES

Purpose: The aim of the present study was to assess the gingival and periodontal status of patients with maxillofacial trauma and to determine the need for periodontal treatment after removal of the intramaxillary fixation. Material and methods: The study included 36 patients with a fracture of the lower jaw. After the clinical and radiological examination of the patients, treatment was performed on a case-by-case basis. 30 days after fixation and removal of the wire ligatures of the patients, the oral-hygienic and periodontal status was assessed using the following indices: simplified oral hygiene index, gingival bleeding index, community periodontal index of treatment needs and evaluation of oral malodour. Results: The most common cause of fractures is a traffic accident, followed by domestic injuries. The level of oral hygiene immediately after removal of the wire ligatures and intermaxillary fixation varied between relatively good and poor, with a greater number of patients having poor hygiene (OHI-S ≥5). The periodontal status of the patients, measured by CPITN, also showed a statistically significant level of clinically established periodontal destruction. Halitosis was detected in all patients. Conclusions: The course of the healing process in the alveolar bone and the functional rehabilitation of patients with mandibular fractures depends not only on the type of surgical treatment for immobilization of the fragments but also on the maintenance of optimal oral hygiene.

Bridging the gap: Compressing non-unions for proper cellular signaling

Non-unions of fractured bones are long-lasting painful conditions with a large socio-economic burden. Surgical intervention is the only treatment option, with firm compression of the bone fragments often resulting in non-union healing. Why compression works as a treatment for non-unions, however, remains poorly understood, because static loading is generally considered as non-osteogenic.In recent years, the crucial role of osteocytes and specific molecular pathways like the RankL/OPG, BMP and Sclerostin/Dkk1/Wnt axes have been identified as critical for bone healing. Furthermore, the role of mechanical loading and osteocyte deformation leading to a decrease or complete blocking of Sclerostin secretion – which in turn leads to activation of the osteogenic Wnt signaling pathway, has been elucidated.Our hypothesis states that osteocytes are the primary mediators of non-union healing. Therefore, in order to switch the resting osteocytes towards an osteogenic mode, firm compression of bone fragments is required for successful treatment of non-unions. This compression is necessary in order to restore the mechanical continuity of the bone, so that activities of daily life can physically stimulate the osteocytes, which in turn direct the bone healing process.

TGF-1 biomarker level evaluation on fracture healing in a murine model with a bone defect after stromal vascular fraction application.

Aim Bone defect is a challenge even for experienced orthopaedic surgeons and it is a significant cause of morbidity in patients and a source of high economic burden in health care. A severe bone defect is a condition whereby the bone tissue cannot undergo natural healing despite surgical stabilization and requires further surgical intervention. Stromal vascular fraction (SVF) is a heterogeneous cell population derived from adipose tissue that results from minimal manipulation of the adipose tissue itself. TGF is essential in maintaining and expanding mesenchymal stem cells or progenitors of osteoblasts. Furthermore, TGF-β signalling also triggers osteoprogenitor cell proliferation, early differentiation, and maintenance of osteoblasts in the bone healing process. The aim of this study was to determine the effect of administering SVF on bone defects' healing process assessed based on the TGF- β1. Methods This was an animal study involving twelve Wistar strain Rattus norvegicus. They were divided into three groups: negative group (normal rats), positive group (rats with bone defect without SVF application), and SVF group (rats with bone defect with SVF application). After 30 days, the rats were sacrificed, the TGF- β1 biomarker was evaluated (quantified using ELISA). Results TGF- β1 biomarker expressions were higher in the group with SVF application than in the group without SVF application. All comparisons of the SVF group and positive control group showed significant differences (p=0,000), respectively. Conclusion Giving SVF application could aid the healing process in a murine model with bone defect, marked by an increased level of TGF- β1.