Implantation of bovine hydroxyapatite and secretome with different oxygen concentration may improve massive bone defect regeneration: An experimental study on animal model

2021 ◽  
pp. 088532822110518
Author(s):  
Taufin Warindra ◽  
Mouli Edward ◽  
Kukuh Dwiputra Hernugrahanto ◽  
Fedik Abdul Rantam ◽  
Ferdiansyah Mahyudin ◽  
...  

The most widely used biomaterials in the treatment of massive bone defects are allograft bone or metal implants. The current problem is that the availability of allographs is limited and metal implants are very expensive. Mass production of secretome can make bone reconstruction of massive bone defects using a scaffold more effective and efficient. This study aims to prove bone regeneration in massive bone defects using bovine hydroxyapatite reconstruction with normoxic and hypoxic secretome conditions using collagen type 1 (COL1), alkaline phosphate (ALP), osteonectin (ON), and osteopontin (OPN) parameters. This is an in vivo study using male New Zealand white rabbits aged 6–9 months. The research was carried out at the Biomaterials Center—Tissue Bank, Dr. Soetomo Hospital for the manufacturer of bovine hydroxyapatite (BHA) and secretome BM-MSC culture under normoxic and hypoxic conditions, and UNAIR Tropical Disease Institute for implantation in experimental animals. Data analysis was carried out with the one-way ANOVA statistical test and continued with the Post Hoc test LSD statistical test to determine whether or not there were significant differences between groups. There were significant differences between hypoxic to normoxic group and hypoxic to BHA group at day-30 observation using ALP, COL 1, ON, and OPN parameters. Meanwhile, there is only osteonectin parameter has significant difference at day-30 observation. At day-60 observation, only OPN parameter has significant differences between hypoxic to normoxic and hypoxic to BHA group. Between day-30 and day-60 observation, BHA and normoxic groups have a significant difference at all parameters, but in hypoxic group, there are only difference at ALP, COL 1, and ON parameters. Hypoxic condition BM-MSC secretome with BHA composite is superior and could be an option for treating bone defect.

2007 ◽  
Vol 330-332 ◽  
pp. 1165-1168
Author(s):  
Jin Feng Yao ◽  
Y.Z. Zhang ◽  
C.Y. Bao ◽  
L.Y. Sun ◽  
X.M. Hao ◽  
...  

The purpose of this study was to explore the feasibility of repairing massive bone defect with in vivo tissue engineering(TE) bone, and to provide experimental evidence for the application of in vivo TE bone into clinic in the future. Six calcium phosphate ceramics (Ca-P ceramics) columns were prepared, and then immersed in dynamic revised simulated body fluid (RSBF). 72 hours later, the bone-like apatite was formed on the surface and pore walls of ceramics. Three dogs were used in this study. Two ceramic columns were implanted bilaterally in the femoral muscles of each dog to construct living bone graft of in vivo TE bone. 6 weeks after implantation, they were transplanted to the box-like bone defects sites created in bilateral mandible of the same animals. The dogs were sacrificed at 8, 12 week after operation respectively. Samples were harvested for gross observation, X-ray examination, tetracycline fluorescence labeling, SPECT and histological observation. These results demonstrated that as a living bone graft, in vivo TE bone participated in the bone metabolism of host, and integrated with the host bone. It is feasible to reconstruct box-like bone defect of mandible with the in vivo TE bone.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yicun Wang ◽  
Hui Jiang ◽  
Zhantao Deng ◽  
Jiewen Jin ◽  
Jia Meng ◽  
...  

Background. To compare the salvage rate and complication between internal fixation and external fixation in patients with small bone defects caused by chronic infectious osteomyelitis debridement. Methods. 125 patients with chronic infectious osteomyelitis of tibia fracture who underwent multiple irrigation, debridement procedure, and local/systemic antibiotics were enrolled. Bone defects, which were less than 4 cm, were treated with bone grafting using either internal fixation or monolateral external fixation. 12-month follow-up was conducted with an interval of 3 months to evaluate union of bone defect. Results. Patients who underwent monolateral external fixation had higher body mass index and fasting blood glucose, longer time since injury, and larger bone defect compared with internal fixation. No significant difference was observed in incidence of complications (23.5% versus 19.3%), surgery time (156±23 minutes versus 162±21 minutes), and time to union (11.1±3.0 months versus 10.9±3.1 months) between external fixation and internal fixation. Internal fixation had no significant influence on the occurrence of postoperation complications after multivariate adjustment when compared with external fixation. Furthermore, patients who underwent internal fixation experienced higher level of daily living scales and lower level of anxiety. Conclusions. It was relatively safe to use internal fixation for stabilization in osteomyelitis patients whose bone defects were less than 4 cm and infection was well controlled.


2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Michal Kosinski ◽  
Anna Figiel-Dabrowska ◽  
Wioletta Lech ◽  
Lukasz Wieprzowski ◽  
Ryszard Strzalkowski ◽  
...  

Objective. Bone defects or atrophy may arise as a consequence of injury, inflammation of various etiologies, and neoplastic or traumatic processes or as a result of surgical procedures. Sometimes the regeneration process of bone loss is impaired, significantly slowed down, or does not occur, e.g., in congenital defects. For the bone defect reconstruction, a piece of the removed bone from ala of ilium or bone transplantation from a decedent is used. Replacement of the autologous or allogenic source of the bone-by-bone substitute could reduce the number of surgeries and time in the pharmacological coma during the reconstruction of the bone defect. Application of mesenchymal stem cells in the reconstruction surgery may have positive influence on tissue regeneration by secretion of angiogenic factors, recruitment of other MSCs, or differentiation into osteoblasts. Materials and Methods. Mesenchymal stem cells derived from the umbilical cord (Wharton’s jelly (WJ-MSC)) were cultured in GMP-grade DMEM low glucose supplemented with heparin, 10% platelet lysate, glucose, and antibiotics. In vitro WJ-MSCs were seeded on the bone substitute Bio-Oss Collagen® and cultured in the StemPro® Osteogenesis Differentiation Kit. During the culture on the 1st, 7th, 14th, and 21st day (day in vitro (DIV)), we analyzed viability (confocal microscopy) and adhesion capability (electron microscopy) of WJ-MSC on Bio-Oss scaffolds, gene expression (qPCR), and secretion of proteins (Luminex). In vivo Bio-Oss® scaffolds with WJ-MSC were transplanted to trepanation holes in the cranium to obtain their overgrowth. The computed tomography was performed 7, 14, and 21 days after surgery to assess the regeneration. Results. The Bio-Oss® scaffold provides a favourable environment for WJ-MSC survival. WJ-MSCs in osteodifferentiation medium are able to attach and proliferate on Bio-Oss® scaffolds. Results obtained from qPCR and Luminex® indicate that WJ-MSCs possess the ability to differentiate into osteoblast-like cells and may induce osteoclastogenesis, angiogenesis, and mobilization of host MSCs. In animal studies, WJ-MSCs seeded on Bio-Oss® increased the scaffold integration with host bone and changed their morphology to osteoblast-like cells. Conclusions. The presented construct consisted of Bio-Oss®, the scaffold with high flexibility and plasticity, approved for clinical use with seeded immunologically privileged WJ-MSC which may be considered reconstructive therapy in bone defects.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaojie Lian ◽  
Kezheng Mao ◽  
Xi Liu ◽  
Xiumei Wang ◽  
Fuzhai Cui

A novel antibacterial bone graft substitute was developed to repair bone defects and to inhibit related infections simultaneously. This bone composite was prepared by introducing vancomycin (VCM) to nanohydroxyapatite/collagen/calcium sulphate hemihydrate (nHAC/CSH). XRD, SEM, and CCK-8 tests were used to characterize the structure and morphology and to investigate the adhesion and proliferation of murine osteoblastic MC3T3-E1 cell on VCM/nHAC/CSH composite. The effectiveness in restoring infectious bone defects was evaluatedin vivousing a rabbit model of chronic osteomyelitis. Ourin vivoresults implied that the VCM/nHAC/CSH composite performed well both in antibacterial ability and in bone regeneration. This novel bone graft substitute should be very promising for the treatment of bone defect-related infection in orthopedic surgeries.


Author(s):  
Edoardo Borgiani ◽  
Georg N. Duda ◽  
Bettina M. Willie ◽  
Sara Checa

AbstractCritical-sized bone defects are critical healing conditions that, if left untreated, often lead to non-unions. To reduce the risk, critical-sized bone defects are often treated with recombinant human BMP-2. Although enhanced bone tissue formation is observed when BMP-2 is administered locally to the defect, spatial and temporal distribution of callus tissue often differs from that found during regular bone healing or in defects treated differently. How this altered tissue patterning due to BMP-2 treatment is linked to mechano-biological principles at the cellular scale remains largely unknown. In this study, the mechano-biological regulation of BMP-2-treated critical-sized bone defect healing was investigated using a multiphysics multiscale in silico approach. Finite element and agent-based modeling techniques were combined to simulate healing within a critical-sized bone defect (5 mm) in a rat femur. Computer model predictions were compared to in vivo microCT data outcome of bone tissue patterning at 2, 4, and 6 weeks postoperation. In vivo, BMP-2 treatment led to complete healing through periosteal bone bridging already after 2 weeks postoperation. Computer model simulations showed that the BMP-2 specific tissue patterning can be explained by the migration of mesenchymal stromal cells to regions with a specific concentration of BMP-2 (chemotaxis). This study shows how computational modeling can help us to further understand the mechanisms behind treatment effects on compromised healing conditions as well as to optimize future treatment strategies.


Medicina ◽  
2022 ◽  
Vol 58 (1) ◽  
pp. 103
Author(s):  
Nuray Özkahraman ◽  
Nilüfer Bölükbaşı Balcıoğlu ◽  
Merva Soluk Tekkesin ◽  
Yusuf Altundağ ◽  
Serdar Yalçın

Background and Objectives: Dentin grafts have osteoinductive and osteoconductive properties and are considered as an alternative to autogenous graft. This study evaluates the efficacy of autogenous mineralized dentin graft (AMDG) alone or with xenograft and compares it with those of various graft materials used in the treatment of intraosseous bone defects. Materials and Methods: The third incisor teeth of six sheep (2–3 years old) were extracted and AMDG was obtained. Six defects were prepared on each tibia of these six sheep: empty defect (group E); autogenous graft (group A), dentin graft (group D), xenograft (group X), autogenous + xenograft (group A + X) and dentin + xenograft (group D + X). Three sheep in each group were sacrificed in the post-operative 3rd and 6th week and the histologic analyses were performed. Results: The D and D + X groups showed histological features similar to the other groups in the 3rd and 6th weeks. No statistically significant difference was found regarding the rates of new bone formation between the D and D + X groups (p = 1.0) and the other groups at both time intervals (p > 0.05). Conclusions: Similar results observed in this study between groups A, D, X, A + X and D + X demonstrate that AMDG can be successfully used in the treatment of intraosseous bone defects. Further experimental and clinical studies are needed to be able to evaluate the effectiveness of dentin grafts in different types of indications.


2021 ◽  
Vol 64 (6) ◽  
pp. 26-32
Author(s):  
Elena Pavlovschi ◽  
◽  
Alina Stoian ◽  
Grigore Verega ◽  
Viorel Nacu ◽  
...  

Background: The use of bone graft has been a successful step in the treatment of a large number of diseases of the osteoarticular system. But a massive bone defect remains a dilemma for modern reconstructive surgery. Present methods used have a high level of morbidity and complication. Literature indicates the absence of an optimal solution in massive bone defects healing. The aim of this study: to perform an in vivo preliminary study of vascularization of the hind limb in the rabbit model, for obtaining a graft able for further inclusion in the host blood circulation, without immunosuppression by decellularization. Material and methods: The study was performed on the 12 laboratory rabbits. After euthanasia of the rabbit, the femoral and tibiofibular bone was collected without soft tissue, only with the vascular pedicle, and keeping the passage through the vessels. In the abdominal aorta was injected contrast material, with the subsequent preparation of the arterial vessels, succeeded by anatomical, morphological, radiography, and microangiography study of this vascularized bone segment. Results: The principal nutrient artery of the rabbit femur springs from the lateral circumflex femoral artery. The optimal segment for vascularized allografting (the rabbit model) was determined the upper third of the femur with the up to the level of the internal iliac artery. So, it could be used as a bone graft for further conservation and decellularization. Conclusions: The vascularized allogeneic bone without immunosuppression would be a perfect alternative in the treatment of the massive bone defects.


2019 ◽  
Vol 55 (3) ◽  
pp. 176
Author(s):  
Junaidi Khotib ◽  
Cantika SC Lasandara ◽  
Samirah Samirah ◽  
Aniek S Budiatin

Bone is an important organ for supports the body that stores reserve of calcium, phosphorus, and other minerals. In fracture conditions where bleeding, soft tissue edema, nerve damage, and blood vessels around the bone damage happen, they can cause the mobilization of these minerals in the surrounding tissue. One of the efforts made in the treatment of these fractures is reconnection, in which it works by filling of bone defect with a matrix and administration of anti-infection. Biomaterial filling in defective bone is thought to accelerate the healing process of bone fracture and prevent osteomyelitis. For this reason, this study evaluates the acceleration of bone fracture healing using natural hydroxyapatite (NHA) bone filler in rabbits with bone defect model. Fracture modeling was performed by surgical technique and drilling of bones with a 4.2 mm diameter to form a defect in the rabbit femur. Bone implant contained bovine hydroxyapatite-gelatin-glutaraldehyde (BHA implant) or bovine hydroxyapatite-gelatin-glutaraldehyde-gentamicin (BHA-GEN implant) that was inserted in bone defects. 27 rabbits were divided into 3 groups: the control group who had bone defect, the bone defect group was given BHA implant and the bone defect group was given BHA-GEN implant. Observation of osteoclast, osteoblast, osteocyte, BALP level, and bone morphological integrity was carried out on the 14th, 28th, and 42nd days after surgery. Histological observation of rabbit femur showed a significant difference on the number of osteoclast, osteoblast and osteocyte in all three groups. The BALP level also showed a significant difference in the group given the natural BHA bone implant compared to the control group on day 14 (p = 0.0361). Based on the result of the X-ray, there was also a better integration of rabbit femur bone in groups with the use of BHA or BHA-GEN bone implant. Thus, it can be concluded that the use of a natural BHA implant can accelerate the process of bone repair in the fracture of rabbit femur. In addition, BHA implants were compatible as a matrix for supporting the bone cell growth.


Nanomaterials ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 999 ◽  
Author(s):  
Mengying Liu ◽  
Yonggang Lv

Bone defects caused by fracture, disease or congenital defect remains a medically important problem to be solved. Bone tissue engineering (BTE) is a promising approach by providing scaffolds to guide and support the treatment of bone defects. However, the autologous bone graft has many defects such as limited sources and long surgical procedures. Therefore, xenograft bone graft is considered as one of the best substitutions and has been effectively used in clinical practice. Due to better preserved natural bone structure, suitable mechanical properties, low immunogenicity, good osteoinductivity and osteoconductivity in natural bone graft, decellularized and demineralized bone matrix (DBM) scaffolds were selected and discussed in the present review. In vivo animal models provide a complex physiological environment for understanding and evaluating material properties and provide important reference data for clinical trials. The purpose of this review is to outline the in vivo bone regeneration and remodeling capabilities of decellularized and DBM scaffolds in bone defect models to better evaluate the potential of these two types of scaffolds in BTE. Taking into account the limitations of the state-of-the-art technology, the results of the animal bone defect model also provide important information for future design of natural bone composite scaffolds.


2021 ◽  
Vol 10 (7) ◽  
pp. e55110716800
Author(s):  
Mauricio Mitsuo Monção ◽  
Raísa Cavalcante Dourado ◽  
Luísa Queiroz Vasconcelos ◽  
Isabela Cerqueira Barreto ◽  
Roberto Paulo Correia de Araújo

This study analyzes the clinical, macroscopic and radiographic characteristics of a biomaterial with different proportions of wolastonite (W) and tricalcium phosphate (TCP) on bone tissue regeneration during the implantation process of an experimental model of critical bone defects. Fifteen Wistar rats were used, randomly distributed in 5 groups (n = 3), with a bone defect created on an 8.0 mm diameter calvaria. 4 groups received implants with different proportions of W%/TCP%, referred to as W20/TCP80, W40/TCP60, W60/TCP40 and W80/TCP20. The fifth control group (GC) was filled with blood clot only. Clinical evaluation was performed every 24 hours, and after 7 days, the animals were euthanized. The calvaria were dissected and analyzed macroscopically and by radiography. All study groups showed a satisfactory clinical evolution. The macroscopic analysis showed filling of the bone defect with granules surrounded by newly formed tissue, and the radiographic analysis showed different patterns of displacement of the biomaterial. The study concluded that the different proportions of W%/TCP% were well tolerated by the study groups and demonstrated biocompatibility. The enhanced hydrophilic behavior of the W40/TCP60, W60/TCP40 and W80/TCP20 groups favored the application in the experimental model in vivo.


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