108 A CRITICAL-SIZE CRANIOFACIAL BONE DEFECT MODEL IN THE YORKSHIRE PIG

2011 ◽  
Vol 23 (1) ◽  
pp. 159 ◽  
Author(s):  
A. J. Maki ◽  
S. G. Clark ◽  
J. R. Woodard ◽  
M. Goldwasser ◽  
M. B. Wheeler

Substantial and innovative developments in the field of bone tissue engineering have prompted increased demand for suitable pre-clinical large animal models. The pig has several advantages over other non-primate species, including availability, rapid growth, large litters, and similar anatomy and physiology to humans. These characteristics make them ideal models for research in diverse applications such as cardiovascular disease, pharmacological activity testing, and organ transplantation. There has been an increased interest in the use of swine as a model for bone healing and grafting techniques. Maxillofacial surgeons strive to develop the best therapy for large bone defects in the face resulting from tumour resection, congenital abnormalities, and traumatic injuries. Creating a model to study a critical-sized bone defect in the mandible, which does not spontaneously heal without clinical intervention, would be a method to test growth factors and synthetic bone graft therapies. However, the size of bone defect required to create this condition has not been ascertained. In the current study, we examined the in vivo healing response for 4, 8, and 16 weeks of surgically created bone defects in the posterior region of the pig mandible. Yorkshire barrows (n = 12) 6–7 months of age were used for the study. All animal experiments conformed to the University of Illinois Institutional Animal Care and Use Committee (IACUC) guidelines. Animals were maintained under general anaesthesia and transcortical, circular defects with diameters of 6, 10, 16, or 25 mm were created on both sides of the mandible. The presence and amount of calcified tissue was assessed using radiographs and dual energy x-ray absorptiometry (DEXA). Tissue morphology was examined using hard-tissue histological methods and a light microscope. Defect diameters of 6, 10, and 16 mm had completed healing or were in the process of healing within the 16-week timeframe of the study. Compared to controls, average percent differences in bone mineral density, in order of increasing defect size, were 0.62%, 28.1%, and 54.5%, respectively. In contrast, 25 mm diameter defects displayed limited collagenous tissue ingrowth, and the presence of calcified tissue was not detected, as indicated by radiographs and histological staining. As the defect size increased, the time required to heal was prolonged until a critical size was determined and normal bone was not completely regenerated. In conclusion, circular defects in the posterior region of the pig mandible with diameters equal or greater than 25 mm will result in limited healing without additional medical intervention and can be termed critical-sized defects. This porcine model will allow for the rapid development and testing of new approaches for the repair of damaged bone, which is especially prevalent in the craniofacial area. This work was partially supported by the Carle Foundation Hospital (#2007-04072) and the Illinois Regenerative Medicine Institute (IDPH #63080017).

2021 ◽  
Vol 9 (5) ◽  
pp. 232596712110035
Author(s):  
Shigeto Nakagawa ◽  
Wataru Sahara ◽  
Kazutaka Kinugasa ◽  
Ryohei Uchida ◽  
Tatsuo Mae

Background: In shoulders with traumatic anterior instability, a bipolar bone defect has been recognized as an important indicator of the prognosis. Purpose: To investigate bipolar bone defects at primary instability and compare the difference between dislocation and subluxation. Study Design: Cohort study; Level of evidence, 3. Methods: There were 156 shoulders (156 patients) including 91 shoulders with dislocation and 65 shoulders with subluxation. Glenoid defects and Hill-Sachs lesions were classified into 5 size categories on 3-dimensional computed tomography (CT) scans and were allocated scores ranging from 0 (no defect) to 4 points (very large defect). To assess the combined size of the glenoid defect and Hill-Sachs lesion, the scores for both lesions were summed (range, 0-8 points). Patients in the dislocation and subluxation groups were compared regarding the prevalence of a glenoid defect, a bone fragment of bony Bankart lesion, a Hill-Sachs lesion, a bipolar bone defect, and an off-track Hill-Sachs lesion. Then, the combined size of the bipolar bone defects was compared between the dislocation and subluxation groups and among patients stratified by age at the time of CT scanning (<20, 20-29, and ≥30 years). Results: Hill-Sachs lesions were observed more frequently in the dislocation group (75.8%) compared with the subluxation group (27.7%; P < .001), whereas the prevalence of glenoid defects was not significantly different between groups (36.3% vs 29.2%, respectively; P = .393). The combined defect size was significantly larger in the dislocation versus subluxation group (mean ± SD combined defect score, 2.1 ± 1.6 vs 0.8 ± 0.9 points, respectively; P < .001) due to a larger Hill-Sachs lesion at dislocation than subluxation (glenoid defect score, 0.5 ± 0.9 vs 0.3 ± 0.6 points [ P = .112]; Hill-Sachs lesion score, 1.6 ± 1.2 vs 0.4 ± 0.7 points [ P < .001]). Combined defect size was larger in older patients than younger patients in the setting of dislocation (combined defect score, <20 years, 1.6 ± 1.2 points; 20-29 years, 1.9 ± 1.5 points; ≥30 years, 3.4 ± 1.6 points; P < .001) but was not different in the setting of subluxation (0.8 ± 1.0, 0.7 ± 0.9, and 0.8 ± 0.8 points, respectively; P = .885). An off-track Hill-Sachs lesion was observed in 2 older patients with dislocation but was not observed in shoulders with subluxation. Conclusion: The bipolar bone defect was significantly more frequent, and the combined size was greater in shoulders with primary dislocation and in older patients (≥30 years).


2019 ◽  
Vol 7 (11) ◽  
pp. 232596711988534
Author(s):  
Shigeto Nakagawa ◽  
Ryohei Uchida ◽  
Hiroyuki Yokoi ◽  
Wataru Sahara ◽  
Tatsuo Mae

Background: The combination of a glenoid defect and a Hill-Sachs lesion in shoulders with traumatic anterior instability has been termed bipolar bone loss, and the preoperative size of these lesions has been reported to influence postoperative recurrence of instability after arthroscopic Bankart repair. Purpose: To investigate the influence of postoperative bipolar bone defect size on postoperative recurrence of instability. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 64 male collision/contact athletes (69 shoulders) were evaluated for a minimum of 2 years after surgery, and the pre- and postoperative sizes of both lesions (glenoid defect and Hill-Sachs) were evaluated retrospectively with 3-dimensional computed tomography. The sports played by the athletes included rugby (n = 28 shoulders), American football (n = 24 shoulders), and other collision/contact sports (n = 17 shoulders). Glenoid defects and Hill-Sachs lesions were classified into 5 size categories and assigned scores from 0 (no defect) to 4 (very large defect). Patients were then classified according to the total score (sum of the scores for both lesions). The influence of pre- and postoperative bipolar bone defect sizes on recurrence of instability was investigated by using the total scores for bipolar bone defects. The influence of postoperative glenoid morphology (normal preoperative glenoid, preoperative glenoid erosion, bone union after arthroscopic bony Bankart repair [ABBR], or nonunion after ABBR) was also investigated, as well as changes in shoulders with a preoperative off-track Hill-Sachs lesion. Results: Of 69 shoulders, 15 (21.7%) developed recurrent instability after surgery. The postoperative recurrence rate was 0% in shoulders with a total score ≤1, while the recurrence rate was consistently higher in shoulders with a total score ≥2 at both pre- and postoperative evaluation (mean, 28.8% and 32.6%, respectively). Postoperative recurrence was uncommon when there was a normal preoperative glenoid or bone union after ABBR, while it was frequent in shoulders with preoperative glenoid erosion or shoulders with nonunion after ABBR and a total score ≥2. An off-track lesion was recognized in 9 shoulders preoperatively. It was transformed to on-track lesions in 4 of the 5 shoulders showing bone union after ABBR, and there was no recurrence in the 5 shoulders with bone union. In contrast, postoperative recurrence of instability occurred in 3 of the 4 shoulders without bone union. Conclusion: Postoperative recurrence was influenced by the pre- and postoperative size of bipolar bone defects. Recurrence was uncommon if bone union was achieved after ABBR, even if there had been an off-track lesion preoperatively.


2019 ◽  
Vol 47 (12) ◽  
pp. 2803-2808 ◽  
Author(s):  
Yoshinori Hasegawa ◽  
Takayuki Kawasaki ◽  
Shuko Nojiri ◽  
Shogo Sobue ◽  
Takefumi Kaketa ◽  
...  

Background: The size of a glenoid bone defect is responsible for reduction in shoulder stability and is correlated with the number of instability events. Biomechanical studies have suggested that it should be considered concomitantly with the Hill-Sachs lesion as “bipolar” bone defects for assessing structural degradation, but the definitive number of instability events associated with the critical size has not been investigated. Purpose: To (1) confirm that the number of instability events is the predictor of a critical size of bipolar bone defects and (2) demonstrate the cutoff value of the number of instability events for these defects in rugby players with traumatic anterior shoulder instability. Study Design: Cross-sectional study; Level of evidence, 3. Methods: One-hundred forty-four rugby players with anterior shoulder instability underwent morphologic evaluation for glenoid and Hill-Sachs lesions by computed tomography and determination of the critical (a glenoid bone defect of ≥25% or an off-track Hill-Sachs lesion) and subcritical (a glenoid bone defect of ≥13.5%) size of bipolar bone defects. In the primary analysis, the prevalence of the critical and subcritical size of bipolar bone defects was investigated. In the secondary analysis, the authors explored the predictors for these bone defects and determined the cutoff value correlating with the critical and subcritical size of bipolar bone defects by applying receiver operating characteristic curves. Results: The primary analysis revealed that the prevalence of critical and subcritical size of bipolar bone defects was 20.8% and 61.8% of 144 shoulders, respectively. In the secondary analysis, multiple logistic regression analysis demonstrated that the total number of shoulder instability events and dominant shoulder were the significant factors associated with the critical and subcritical size of bipolar bone defects. The cutoff value for the number of instability events that correlated with critical bipolar bone defects was 6 for the dominant and 9 for the nondominant shoulder, whereas it was 4 for the dominant and 5 for the nondominant shoulder for subcritical bipolar bone defects. Conclusion: The number of shoulder instability events and the dominant shoulder were the predictors for the critical and subcritical size of bipolar bone defects for a shoulder with traumatic instability. Four injury events should herald caution when treating rugby players with shoulder instability.


2020 ◽  
Vol 23 (2) ◽  
pp. 62-70 ◽  
Author(s):  
Sae Hoon Kim ◽  
Whanik Jung ◽  
Sung-Min Rhee ◽  
Ji Un Kim ◽  
Joo Han Oh

Background: Recent studies have reported high rates of recurrence of shoulder instability in patients with glenoid bone defects greater than 20% after capsulolabral reconstruction. The purpose of the present study was to evaluate the failure rate of arthroscopic capsulolabral reconstruction for the treatment of anterior instability in the presence of glenoid bone deficits >20%. Methods: Retrospective analyses were conducted among cases with anterior shoulder instability and glenoid bone defects of >20% that were treated by arthroscopic capsulolabral reconstruction with a minimum 2-year follow-up (30 cases). We included the following variables: age, bone defect size, instability severity index score (ISIS), on-/off-track assessment, incidence recurrent instability, and return to sports. Results: The mean glenoid bone defect size was 25.8% ± 4.2% (range, 20.4%–37.2%), and 18 cases (60%) had defects of >25%. Bony Bankart lesions were identified in 11 cases (36.7%). Eleven cases (36.7%) had ISIS scores >6 points and 21 cases (70%) had off-track lesions. No cases of recurrent instability were identified over a mean follow-up of 39.9 months (range, 24–86 months), but a sense of subluxation was reported by three patients. Return to sports at the preinjury level was possible in 24 cases (80%), and the average satisfaction rating was 92%. Conclusions: Arthroscopic soft tissue reconstruction was successful for treating anterior shoulder instability among patients with glenoid bone defects >20%, even enabling return to sports. Future studies should focus on determining the range of bone defect sizes that can be successfully managed by soft tissue repair.


2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Shuai Wei ◽  
Jian-Xiong Ma ◽  
Lai Xu ◽  
Xiao-Song Gu ◽  
Xin-Long Ma

Abstract Compared with non-degradable materials, biodegradable biomaterials play an increasingly important role in the repairing of severe bone defects, and have attracted extensive attention from researchers. In the treatment of bone defects, scaffolds made of biodegradable materials can provide a crawling bridge for new bone tissue in the gap and a platform for cells and growth factors to play a physiological role, which will eventually be degraded and absorbed in the body and be replaced by the new bone tissue. Traditional biodegradable materials include polymers, ceramics and metals, which have been used in bone defect repairing for many years. Although these materials have more or fewer shortcomings, they are still the cornerstone of our development of a new generation of degradable materials. With the rapid development of modern science and technology, in the twenty-first century, more and more kinds of new biodegradable materials emerge in endlessly, such as new intelligent micro-nano materials and cell-based products. At the same time, there are many new fabrication technologies of improving biodegradable materials, such as modular fabrication, 3D and 4D printing, interface reinforcement and nanotechnology. This review will introduce various kinds of biodegradable materials commonly used in bone defect repairing, especially the newly emerging materials and their fabrication technology in recent years, and look forward to the future research direction, hoping to provide researchers in the field with some inspiration and reference.


2019 ◽  
Vol 48 (1) ◽  
pp. 48-55
Author(s):  
Shigeto Nakagawa ◽  
Takehito Hirose ◽  
Ryohei Uchida ◽  
Makoto Tanaka ◽  
Tatsuo Mae

Background: In shoulders with traumatic anterior instability, a bipolar bone defect has recently been recognized as an important indicator of the prognosis. Purpose: To investigate the influence of bipolar bone defects on postoperative recurrence after arthroscopic Bankart repair performed at primary instability. Study Design: Cohort study; Level of evidence, 3. Methods: The study group consisted of 45 patients (45 shoulders) who underwent arthroscopic Bankart repair at primary instability before recurrence and were followed for at least 2 years. The control group consisted of 95 patients (95 shoulders) with recurrent instability who underwent Bankart repair and were followed for at least 2 years. Glenoid defects and Hill-Sachs lesions were classified into 5 size categories on 3-dimensional computed tomography and were allocated scores ranging from 0 for no defect to 4 for the largest defect. The shoulders were classified according to the total score for both lesions (0-8 points). The postoperative recurrence rate was investigated for each score of bipolar bone defects and was compared between patients with primary instability and patients with recurrent instability. The same analysis was performed for the age at operation (<20 years, 20-29 years, or ≥30 years) and for the presence of an off-track Hill-Sachs lesion. Results: Bipolar bone defects were smaller in shoulders with primary instability (mean ± SD defect score, 1.4 ± 1.5 points) than in those with recurrent instability (3.6 ± 1.9 points) and were larger in older patients than in younger patients at the time of primary instability. The postoperative recurrence rate was low (6.7%) in shoulders with primary instability regardless of the size of the bipolar bone defect and the patient’s age, whereas the postoperative recurrence rate was high (23.2%) in shoulders with recurrent instability, especially among patients younger than 20 years with bipolar bone defects of 2 points or greater. An off-track Hill-Sachs lesion was found in only 1 patient in the oldest age group (2.2%) at primary instability, but it was found in 19 patients (20%) at recurrent instability, including 14 patients younger than 30 years. Among patients with an off-track lesion, the postoperative recurrence rate was significantly higher in patients younger than 20 years with recurrent instability (recurrence rates: <20 years, 71.4%; 20-29 years, 14.3%; ≥30 years, 0%). Conclusion: The recurrence rate was consistently low in patients with primary instability and was significantly influenced by bipolar bone defect size and patient age in patients with recurrent instability.


2020 ◽  
Author(s):  
Michael Bouyer ◽  
Charlotte Garot ◽  
Paul Machillot ◽  
Julien Vollaire ◽  
Vincent Fitzpatrick ◽  
...  

Abstractthe reconstruction of large bone defects (12 cm3) remains a challenge for clinicians. We developed a new critical-size mandibular bone defect model on a mini-pig, close to human clinical issues. We analyzed the bone reconstruction obtained by a 3D printed scaffold made of clinical-grade PLA, coated with a polyelectrolyte film delivering an osteogenic bioactive molecule (BMP-2). We compared the results (CT-scan, μCT, histology) to the gold standard solution, bone autograft. We demonstrated that the dose of BMP-2 delivered from the scaffold significantly influenced the amount of regenerated bone and the repair kinetics, with a clear BMP-2 dose-dependence. Bone was homogeneously formed inside the scaffold without ectopic bone formation. The bone repair was as good as for the bone autograft. The BMP-2 doses applied in our study were reduced 20 to 75-fold compared to the commercial collagen sponges used in the current clinical applications, without any adverse effects. 3D printed PLA scaffolds loaded with reduced doses of BMP-2 can be a safe and simple solution for large bone defects faced in the clinic.


Author(s):  
Tie Liu ◽  
Wen Fang ◽  
Gang Wu ◽  
Yining Li ◽  
Janak L. Pathak ◽  
...  

Background: Bone grafts are in high demand due to the increase in the cases of bone defects mainly caused by trauma, old age, and disease-related bone damages. Tissue-engineered calcium phosphate (CaP) biomaterials match the major inorganic contents of bone, thereby could be the potential bone graft substitute. However, CaP-bone grafts lack the osteoinductivity that is vital for effective bone regeneration. In this study, we aimed to test the bone defect healing potential of biomimetically fabricated low dose BMP2-doped CaP (BMP2.BioCaP) grafts in a large animal model.Methods: Low dose BMP2 was doped internally (BMP2-int.BioCaP) or on the surface of CaP (BMP2-sur.BioCaP) grafts during the fabrication process. Our previous study showed the robust bone regenerative potential of BMP2-int.BioCaP and BMP2-sur.BioCaP grafts in the rat ectopic model. In this study, we investigated the bone defect healing potential of BMP2.BioCaP grafts in sheep humerus/femoral defects, as well as compared with that of autologous bone graft and clinically used deproteinized bovine bone (DBB) xenograft.Results: Different ways of BMP2 doping did not affect the surface morphology and degradation properties of the graft materials. Micro-CT and histology results showed robustly higher bone defect-healing potential of the BMP2.BioCaP grafts compared to clinically used DBB grafts. The bone defect healing potential of BMP2.BioCaP grafts was as effective as that of the autologous bone graft. Although, BMP2-int.BioCaP doped half the amount of BMP2 compared to BMP2-sur.BioCaP, its' bone defect healing potential was even robust. The BMP2.BioCaP grafts showed less immunogenicity compared to BioCaP or DBB grafts. The volume density of blood vessel-like and bone marrow-like structures in both BMP2.BioCaP graft groups were in a similar extent to the autologous group. Meticulous observation of higher magnification histological images showed active bone regeneration and remodeling during bone defect healing in BMP2.BioCaP graft groups.Conclusion: The robust bone regenerative potential of BMP2.BioCaP grafts in the ectopic model and in-situ bone defects in small and large animals warrant the pre-clinical studies on large animal critical-sized segmental bone defects.


Author(s):  
Azimah Ahmad Zainol Hady ◽  
Liyana Azmi ◽  
Amira Raudhah Abdullah

Bone can heal on its own through the process known as bone remodelling. Nonetheless, a critical size bone defect will hinder the natural bone-healing process and may not allow for complete fracture healing. These requires surgical intervention by employing the use of bone tissue implants and in need of realignment and fixation for proper fracture healing. Traditional knowledge of bone injury and fracture healing must be comprehended thoroughly for a proper invention of bioengineered material or devices that could enhance the physiological process. Heretofore, engineered materials used to address critical size bone defects have encountered various challenges and improvement be it in bone grafting or choices of mechanical stabilization devices. To date, researchers have been mainly focussing on the alternative material for bone graft substitute albeit the selection of fixators to establish mechanical stabilization are as important. This review highlighted the challenges, improvement and advancement in mechanical stabilization devices and bone graft substitute with respect to the physiological process of bone fracture healing. Identifying these challenges would help assist the researcher in an expedition toward the recovery and restoration of critical size bone defects.


2019 ◽  
Vol 9 (10) ◽  
pp. 1441-1447
Author(s):  
Yucheng Li ◽  
Jiang Xin ◽  
Wencai Sun

Bone marrow mesenchymal stem cells (BMSCs) have characteristics of self-renewal and multidirectional differentiation. LncRNA UCA1 regulates BMSCs differentiation. Whether LncRNA UCA1 plays a role in bone defects remains unclear. BMSCs were randomly divided into control group, radiation group (6Gy), radiation + UCA1 group followed by analysis of the expression of LncRNA UCA1, RUNX2 and OPN by real time PCR, BMSCs proliferation by MTT assay as well as ALP activity. Healthy Sprague-Dawley rats were randomly divided into control group; bone defect group; UCA1 group, in which UCA1-transfected BMSCs were infused into bone defect rats followed by analysis of bone mineral density, ALP activity as well as the formation of type II collagen by ELISA. LncRNA UCA1 expression was significantly decreased in BMSCs of irradiated group, with decreased BMSCs proliferation, reduced expression of RUNX2 and OPN as well as decreased ALP activity (P < 0.05). Transfection of UCA1 significantly up-regulated LncRNA UCA1 expression in BMSCs, promoted BMSCs proliferation, increased the expression of RUNX2 and OPN, and the activity of ALP (P < 0.05). In addition, UCA1 promoted bone mineral density, increased ALP activity and type II collagen formation in rats with bone defect. LncRNA UCA1 promotes osteogenic differentiation of BMSCs, and targeting it might be a novel approach to promote bone remodeling at the bone defect site.


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