Immature Rabbits Research Articles

Assessing early left ventricular remodeling in pediatric hypertension: A study using transthoracic echocardiography combined with two‐dimensional speckle tracking echocardiography in an immature rabbit model

Assessing early left ventricular remodeling in pediatric hypertension: A study using transthoracic echocardiography combined with two‐dimensional speckle tracking echocardiography in an immature rabbit model

Subperiosteal delivery of transforming growth factor beta 1and human growth hormone from mineralized PCL films.

The ability to locally deliver bioactive molecules to distinct regions of the skeleton may provide a novel means by which to improve fracture healing, treat neoplasms or infections, or modulate growth. In this study, we constructed single-sided mineral-coated poly-ε-caprolactone membranes capable of binding and releasing transforming growth factor beta 1 (TGF-β1) and human growth hormone (hGH). After demonstrating biological activity in vitro and characterization of their release, these thin bioabsorbable membranes were surgically implanted using an immature rabbit model. Membranes were circumferentially wrapped under the periosteum, thus placed in direct contact with the proximal metaphysis to assess its bioactivity in vivo. The direct effects on the metaphyseal bone, bone marrow, and overlying periosteum were assessed using radiography and histology. Effects of membrane placement at the tibial growth plate were assessed via physeal heights, tibial growth rates (pulsed fluorochrome labeling), and tibial lengths. Subperiosteal placement of the mineralized membranes induced greater local chondrogenesis in the plain mineral and TGF-β1 samples than the hGH. More exuberant and circumferential ossification was seen in the TGF-β1 treated tibiae. The TGF-β1 membranes also induced hypocellularity of the bone marrow with characteristics of gelatinous degeneration not seen in the other groups. While the proximal tibial growth plates were taller in the hGH treated than TGF-β1, no differences in growth rates or overall tibial lengths were found. In conclusion, these data demonstrate the feasibility of using bioabsorbable mineral coated membranes to deliver biologically active compounds subperiosteally in a sustained fashion to affect cells at the insertion site, bone marrow, and even growth plate.

Overgrowth of long bone in rabbits by growth stimulation through metaphyseal hole creation

Overgrowth of long bones was noted in pediatric patients who underwent anterior cruciate ligament reconstruction. Hyperaemia during creating a metaphyseal hole and the microinstability made by the drill hole may induce overgrowth. This study aimed to determine whether metaphyseal hole creation accelerates growth and increases bone length and compare the effects of growth stimulation between metaphyseal hole creation and periosteal resection. We selected 7- to 8-week-old male New Zealand white rabbits. Periosteal resection (N = 7) and metaphyseal hole creation (N = 7) were performed on the tibiae of skeletally immature rabbits. Seven additional sham controls were included as age-matched controls. In the metaphyseal hole group, the hole was made using a Steinman pin at the same level of periosteal resection, and the cancellous bone beneath the physis was removed by curettage. The vacant space in the metaphysis below the physis was filled with bone wax. Tibiae were collected 6 weeks after surgery. The operated tibia was longer in the metaphyseal hole group (10.43 ± 0.29 cm vs. 10.65 ± 0.35 cm, P = 0.002). Overgrowth was higher in the metaphyseal hole group (3.17 ± 1.16 mm) than in the sham group (− 0.17 ± 0.39 mm, P < 0.001). The overgrowth in the metaphyseal hole group was comparable to that in the periosteal resection group (2.23 ± 1.52 mm, P = 0.287). In rabbits, metaphyseal hole creation and interposition with bone wax can stimulate long bone overgrowth, and the amount of overgrowth is similar to that seen in periosteal resection.

A Novel Model of Hip Femoroacetabular Impingement in Immature Rabbits Reproduces the Distinctive Head-Neck Cam Deformity

Background: Femoroacetabular impingement (FAI) is a leading cause of hip pain in young adults and often leads to degenerative osteoarthritis (OA). A small animal model of hip deformities is crucial for unraveling the pathophysiology of hip OA secondary to FAI. Purposes: To (1) characterize a new minimally invasive surgical technique to create a proximal femoral head–neck deformity in a skeletally immature rabbit model and (2) document the effect of an injury to the medial proximal femoral epiphysis on head–neck morphology at 28 days after the injury. Study Design: Controlled laboratory study. Methods: Six-week-old New Zealand White rabbits (n = 10) were subjected to right hip surgery, with the left hip used as a control. An epiphyseal injury in the medial femoral head was created using a 1.6-mm drill. Hips were harvested bilaterally at 28 days after surgery. Alpha and epiphyseal shaft angles were measured on radiographs. Alpha angles at the 1- and 3-o’clock positions were measured on the oblique axial plane of micro–computed tomography images. Bone bar formation secondary to growth plate injuries was confirmed using alcian blue hematoxylin staining. Results: All hips in the study group showed a varus–type head-neck deformity, with lower epiphyseal shaft angles on anteroposterior radiographs versus those in the control group (133°± 8° vs 142°± 5°, respectively; P = .022) and higher epiphyseal shaft angles on lateral radiographs (27°± 12° vs 10°± 7°, respectively; P < .001). The mean alpha angles in the study group were higher at both the 1- (103°± 14° vs 46°± 7°, respectively; P < .002) and 3-o’clock (99°± 18° vs 35°± 11°, respectively; P < .002) positions than those in the control group. Alcian blue hematoxylin staining of all hips in the study group indicated that the injured physis developed a bony bar, leading to growth plate arrest on the medial femoral head. Conclusion: The proposed model led to growth arrest at the proximal femoral physis, resulting in a femoral head–neck deformity similar to human FAI. Clinical Relevance: Our novel small animal model of a femoral head–neck deformity is a potential platform for research into the basic mechanisms of FAI disease progression and the development of disease–modifying therapies.

Radial shockwave treatment promotes chondrogenesis in human growth plate and longitudinal bone growth in rabbits.

The process of longitudinal bone growth occurs at the growth plate where the chondrocytes undergo apparent structural and molecular changes to promote growth. Recent reports suggest that radial shockwave treatment (rSWT) stimulates bone length in cultured fetal rat metatarsals. Therefore, we investigated if rSWT has similar growth promoting effects on cultured human growth plate fragments and addressed the same in a preclinical in vivo rabbit model by subjecting their growth plates to rSWT. Short-term effects of high-energy rSWT were evaluated in a unique model of cultured human growth plate cartilage (n=5) wherein samples exposed to rSWT were assessed for chondrogenic markers at 24h in comparison to unexposed samples obtained from the same limb. Local in vivo effects were studied in six-week-old rabbits who had their distal femurs exposed to four weekly sessions of rSWT at low- and high-energy levels (n=4 each). At sacrifice, histomorphometric and immunohistochemistry analyses were performed. For effect on longitudinal growth, proximal tibiae of 22-week-old rabbits (n=12) were asymmetrically exposed to rSWT; the contralateral side served as untreated controls. At sacrifice, the final bone length was measured. In the ex vivo model of cultured human growth plate cartilage, rSWT exposure upregulated SOX9 and COL2A1 compared to control. In the immature rabbit model, an increased number of proliferative chondrocytes and column density was seen for both the energy levels. In the adolescent rabbits, an increase in tibial length was observed after the fourth session of high-energy rSWT and until six-weeks after rSWT compared to the untreated limb. Our preliminary experimental results suggest that rSWT may serve as a non-invasive treatment and possibly a safe strategy to stimulate longitudinal bone growth. However, further studies are needed to assess the in vivo effects of rSWT in models of disturbed bone growth.

THE ROUND LIGAMENT IN DEVELOPMENTAL HIP DYSPLASIA: ARE ITS MECHANICAL AND HISTOLOGICAL PROPERTIES PRESERVED?

ABSTRACTIntroduction During open surgical dislocated hip reduction, several anatomical structures, such as the round ligament, are approached. However, there is controversy over both the possibility of preserving the ligament and its functional importance.Materials and Methods This experimental study used skeletally immature rabbits as a model for congenital hip dislocation. Thirty-six rabbits comprised the sample that was submitted to the round ligament analysis. The sample was stratified for analysis (biomechanics, zymography, histology, and immunohistochemistry). Statistical analysis compared the unstable side to the control side of each rabbit.Results Biomechanical assays showed that the mean maximal strength of the round ligament on the unstable side was similar to that of the control side (p = 0.594), which was also the case with maximum deformation (p = 0.328). Histologically, there was a statistically significant increase in cellularity on the unstable side (p <0.001). Additionally, there was significantly greater collagen occupancy on the control side (p <0.001). Zymography revealed no significant difference in the amount of active metalloproteinase 2 (MMP-2) (p = 0.068).Conclusions Although histological analysis found evidence of significant changes in the RL in unstable hips, there were no significant differences in zymography, and no changes were observed in biomechanical tests. Evidence Level V; Experimental study.

İNSAN AMNİYOTİK SIVISI VE MEMBRANININ BİR TAVŞAN DİZİ KIKIRDAK DEFEKTİ MODELİNDE KONDRAL İYİLEŞME ÜZERİNE ETKİLERİ

Objective&#x0D; Due to the limited intrinsic healing and repair capacity&#x0D; of the articular cartilage, most treatment methods&#x0D; cannot achieve reliable regeneration of normal&#x0D; hyaline cartilage, resulting in early development&#x0D; of osteoarthritis. The purpose of this study was to&#x0D; determine the effects of human amniotic fluid and&#x0D; membrane on chondral defects.&#x0D; Material and Methods&#x0D; Sixty-four knees of 32 immature New Zealand rabbits&#x0D; were included in the study. Full thickness chondral&#x0D; defects were created in the weight-bearing surface of&#x0D; the medial condyles of the rabbits. The rabbits were&#x0D; divided randomly into four groups: no adjunct treatment&#x0D; was given in group 1, 0.3 ml human amniotic fluid&#x0D; (HAF) alone in group 2, human amniotic membrane&#x0D; (HAM) alone in group 3 and both of 0.3 ml HAF and&#x0D; HAM in group 4 was administered. The condyles were&#x0D; histopathologically evaluated at 4th and 12th week&#x0D; using the modified O’Driscoll Grading Scale.&#x0D; Results&#x0D; There were no significant differences in the quality&#x0D; of the regenerated tissue within and between groups&#x0D; (p&gt;0.05). The mean results of groups at the 12th week&#x0D; were worse than results at the 4th week; however,&#x0D; the difference was statistically significant for only the&#x0D; sham group (group 1) and the combined therapy&#x0D; group (group 4) (p=0.007 and p=0.014, respectively).&#x0D; Conclusion&#x0D; HAF alone, HAM alone, and combined administration&#x0D; of both biomaterials neither affected chondral defect&#x0D; healing nor had any differences between each&#x0D; other. Nevertheless, we believe that some early&#x0D; regeneration due to an intrinsic repair mechanism is&#x0D; possible in immature rabbits as this study showed&#x0D; better results at 4th week than those at 12th week,&#x0D; although they are prone to degenerative processes in&#x0D; long-term follow-up. We suggest that a larger sample&#x0D; size in an experimental study would probably display&#x0D; a statistically significant difference when investigating&#x0D; effects of HAF, HAM, or both.

Histologically Confirmed Recellularization is a Key Factor that Affects Meniscal Healing in Immature and Mature Meniscal Tears.

Healing outcomes of meniscal repair are better in younger than in older. However, exact mechanisms underlying superior healing potential in younger remain unclear from a histological perspective. This study included 24 immature rabbits and 24 mature rabbits. Tears were created in the anterior horn of medial meniscus of right knee in each rabbit. Animals were sacrificed at 1, 3, 6, and 12 weeks postoperatively. We performed macroscopic and histological evaluations of post-meniscal repair specimens. Cells were counted within a region of interest to confirm cellularization at tear site in immature menisci. The width of cell death zone was measured to determine the region of cell death in mature menisci. Apoptosis was evaluated by TUNEL assay. Vascularization was assessed by CD31 immunofluorescence. The glycosaminoglycans and the types 1 and 2 collagen content was evaluated by calculating average optical density of corresponding histological specimens. Cartilage degeneration was also evaluated. Healing outcomes following untreated meniscal tears were superior in immature group. Recellularization with meniscus-like cell morphology was observed at tear edge in immature menisci. Superior recellularization was observed at meniscal sites close to joint capsule than at sites distant from the capsule. Recellularization did not occur at tear site in mature group; however, we observed gradual enlargement of cell death zone. Apoptosis was presented at 1, 3, 6, 12 weeks in immature and mature menisci after untreated meniscal tears. Vascularization was investigated along the tear edges in immature menisci. Glycosaminoglycans and type 2 collagen deposition were negatively affected in immature menisci. We observed glycosaminoglycan degradation in mature menisci and cartilage degeneration, specifically in immature cartilage of the femoral condyle. In conclusion, compared with mature rabbits, immature rabbits showed more robust healing response after untreated meniscal tears. Vascularization contributed to the recellularization after meniscal tears in immature menisci. Meniscal injury fundamentally alters extracellular matrix deposition.

Oral Spermine Supplementation in Gestated Rabbit: A Study on Villi Height of Immature Intestines.

Introduction: Immature intestines are the major problem in prematurity. Postnatal oral spermine has been shown in studies to improve intestinal maturation in rats and piglets. This study aimed to find out the efficacy of spermine in rabbits during gestation.Method: An experimental study was done in an unblinded, randomized manner on those treated with and without spermine administration. A morphological examination of hematoxylin–eosin-stained villi was performed under a light microscope with a focus on villi height. Data were subjected to analysis.Results: The median of the spermine-treated group was found to be higher at 24, 26, and 28 days than the non-spermine group, but was not significantly different.Conclusion: Oral spermine supplementation during gestation might improve intestinal villi height in immature rabbit intestines.

Growth Modulation by Stimulating the Growth Plate: A Pilot Study

This study investigates the ability of low-intensity pulsed ultrasound (LIPUS) or direct injection of recombinant growth hormone (rGH) to stimulate local growth of long bones. In a randomized controlled animal trial, healthy immature rabbits were allocated to 1 of the following 4 conditions: epiphyseal rGH periosteal injection, transdermal LIPUS, saline periosteal injection, or no treatment. New bone deposition was labeled with calcein at days 1 and 18, and microscopic measurements of growth were conducted by blinded observers. Statistically significant differences in growth were observed between the LIPUS and rGH stimulated legs compared with contralateral control legs (35% p = 0.04 and 41% p = 0.04, respectively); whereas no difference was observed between the 4 control groups (p = 0.37). There was no evidence of physeal bar formation, suggesting that direct injection of rGH and application of LIPUS around the distal femoral physis in rabbits may have a positive effect on microscopic growth without short-term adverse sequelae.

Population Pharmacokinetic Modelling of Orally Administered Doxycycline to Rabbits at Different Ages.

Doxycycline is a well-tolerated tetracycline antibiotic, registered for use in rabbits and administered for treatment of bacterial infections in this animal species. Nevertheless, the available pharmacokinetic data are limited and this study aimed to investigate the pharmacokinetics of orally administered doxycycline in mature and immature rabbits by application of the population approach. The rabbits were treated orally with doxycycline hyclate (5 mg/kg bw) in the form of a solid gelatin capsules. Free plasma concentrations were determined with HPLC analysis with Photodiode array detection. The estimated typical value of volume of distribution (tvV), total body clearance, and absorption rate constant were 4.429 L/kg, 1.473 L/kg/h, and 0.257 h−1, respectively. The highest between-subject variability (BSV) of 69.30% was observed for tvV. Co-variates such as body weight, age, and biochemical parameters did not improve the tested model and did not contribute to explanation of the BSV. The population pharmacokinetic model of the orally administered doxycycline in rabbits should be further developed by addition of data from more animals treated with higher doses. An oral dose of 5 mg/kg could ensure percentage of the time from the dosing interval during which the concentration is above minimum inhibitory concentration (MIC) %fT > MIC of 35% if MIC of 0.18 μg·mL−1 and a dosing interval of 12 h is assumed which does not cover criteria for rational use of antibiotics.

Restoration of surfactant activity by polymyxin B in lipopolysaccharide-potentiated injury of immature rabbit lungs

During postnatal adaptation pulmonary surfactant may be inactivated by lipopolysaccharide (LPS). We evaluated the effect of surfactant therapy in combination with antibiotic polymyxin B (PxB) in double-hit model of neonatal lung injury. Surfactant (poractant alfa, Curosurf) was exposed to smooth (S) LPS without/with PxB and tested in captive bubble surfactometer. Preterm rabbits received intratracheally saline (control) or S-LPS and were ventilated with 100% oxygen. After 30 min, LPS-treated animals received no treatment, or surfactant (200 mg/kg) without/with 3% PxB; controls received the same dose of surfactant. Animals were ventilated for further 2 h. In vitro, addition of 5% S-LPS to surfactant increased minimum surface tension (γmin) and addition of 1–3% PxB to surfactant/S-LPS mixture restored γmin to low values. Animals only given S-LPS had lower lung compliance and lung gas volume (LGV) compared to surfactant groups. Treatment with surfactant/PxB, but not with surfactant only, restored LGV. Addition of PxB to the surfactant increased the alveolar expansion. S-LPS interferes with surface activity of the pulmonary surfactant and PxB improves the resistance of surfactant to LPS-induced inactivation. In our neonatal model of respiratory distress syndrome surfactant gives positive response even in simultaneous exposure to S-LPS, when enriched with PxB.

Thoracic vertebral morphology in normal and scoliosis deformity in skeletally immature rabbits: A Longitudinal study.

ObjectiveTo measure age‐related changes in thoracic vertebral body heights (VBH) in skeletally immature normative and scoliotic rabbits to assess how VBH change during growth. To examine the potential link between the moment‐arm of the rib tether and vertebral wedging as well as the sum of the curvature angles at the apical level (T7). To assess the correlation between the magnitude of initial spine curve and final spine curve in the scoliotic group.MethodsEight healthy, skeletally immature normative New Zealand rabbits and ten skeletally immature scoliotic rabbits which underwent unilateral rib tethering were included retrospectively. Each rabbit was scanned at two to four time points (at 7, 11, 14 and 28 weeks). Three dimensional bone models of thoracic vertebrae (T1‐T12) were digitally segmented and reconstructed. VBH were calculated using surface landmark points from each thoracic vertebra. Apical level (T7) ± 2 levels in scoliotic rabbits were compared to their corresponding levels and time points in the normative group. The moment‐arms between the centroids of 2D projections of T3‐T9 vertebral bodies and the line which connects the centroids of the end levels were calculated.ResultsBilateral left‐right (L‐R) symmetry and anterior‐posterior (A‐P) asymmetry were observed in normative VBH. Bilateral concave‐convex (CC‐CX) asymmetry and (A‐P) asymmetry were observed in scoliotic VBH. No significant differences in growth rates were found between the normative and scoliotic groups. Vertebral wedging as well as curvature magnitude were positively correlated with the moment‐arms.ConclusionUnilateral rib tether applies compressive forces on both concave and convex sides, whereas compressive forces are lower on the latter. Knowing the amount of vertebral wedging or curve magnitude would enable us to predict the applied force (moment‐arms), which is important for planning a corrective surgery.

Otoprotective Effect of Cortexin, Cogitum, and Elkar Administered Simultaneously with Netromycin in the Experiment.

We studied possible otoprotective effect of drugs widely used for the correction of perinatal hypoxic brain damage in premature infants. The experiments were carried out on immature rabbits with an immature hearing organ. The auditory function was assessed by DPOAE and ABR methods in intact animals and rabbits treated with therapeutic doses of netromycin alone or in combination with the drugs that normalize metabolic processes in the brain (Cortexin, Cogitum, Elkar, vitamin B2, ATP, and cocarboxylase). It was found that the administered drugs produced an otoprotective effect and reduced the severity, but did not eliminate the ototoxic effect.

Subcutaneous grafting of ovaries from newborn rabbits into adult ovariectomized mice does not result in normal folliculogenesis

About 10% (6.1 million) of women in the United States ages 15–44 have difficulty becoming pregnant or staying pregnant. About 1/3 are fertility problems in women. Abnormal ovarian function is a major contributor. A greater understanding of ovarian function and especially follicular development would improve treatment. Follicles form when germ cells arrive in the primitive sex cords, which are derived from the coelomic epithelium. In most species, these cords fragment and the germ cells become covered by precursors of the granulosa cells. Thus primordial follicles form. Pools of these follicles are eventually recruited and undergo maturation; a series of functional and morphological transformations that lead to ovulatory follicles. In species like humans, cattle and pigs, follicles form during the embryonic phase of gestation, while maturation takes place after birth. In contrast, both phases occur postnatally in rabbits and makes them an excellent model to study folliculogenesis. Laboratory studies using non‐rodent species are logistically more difficult and even prohibitive. One alternative is ovarian grafting into immunocompromised mice. When adult ovarian tissue is transplanted from large animals into mice, some primordial follicles survive and undergo maturation. We investigated the rabbit model by transplantation of immature rabbit ovaries under the dorsal skin of adult ovariectomized NCr N ude mice (1 ovary / mouse). At 4 – 5 weeks, growth of the grafted ovaries was evident. Macroscopically, 50% of the grafts (5/10) had one or two follicle‐like structures on their surface. Histologically the structures were cysts lined by cuboidal cells and contained cells with the germ cell phenotype. In conclusion, ovaries grafted subcutaneously from newborn rabbits into ovariectomized adult mice developed cystic primordial follicles. Normal follicle formation and maturation did not occur.Support or Funding InformationMidwestern University intramural funds

The effect of increased femoral anteversion on the morphological and trabecular microarchitectural changes in the trochlea in an immature rabbit

Increased femoral anteversion (FA) has been recently demonstrated as one risk factor for recurrent patellar dislocation (RPD). However, it has been still unclear whether the increase of FA can result in patellar dislocation, and subsequent morphological and trabecular microarchitectural changes in the trochlea has not been investigated. Forty knees from 20 rabbits at 3 months of age were included. The right knees underwent surgery with internal rotation of distal femur to increase FA, with the left knees acting as internal controls. The surgical knees were called operated group, and non-operated knees were control group. Micro-CT scans for distal femur were acquired after 4 months of surgery. In the operated group, a boss located proximal to the entrance of the groove was formed. The central trochlear height was significantly greater, sulcus angle was significantly greater, both lateral and medial trochlear slope were significantly lower, and boss height was significantly greater in comparison to the control group. Regarding the microarchitectural changes, the trabecular thickness were increased by 67.5% at the groove, 33.0% and 29.5%, at the medial and lateral femoral condyle, and trabecular number were decreased by 37.8% and 26.5% at the groove and medial femoral condyle. This study provided a novel animal model of trochlea dysplasia by femoral rotational osteotomy and increased FA. These changes were associated with the load redistribution in the patellofemoral joint after the increase of FA.

EFFECT OF OMEGA 3 ON THE REPRODUCTIVE PERFORMANCE OF THE ALGERIAN SYNTHETIC RABBIT IN ARTIFICIAL INSEMINATION

In the present work of the pubescent and immature rabbit does of the Algerian synthetic strain (ITELV 2006), the animals received a supplement of omega 3 of animal origin (fish oil) or vegetable origin (linseed) for 3 months (2 months before AI and 1 month during pregnancy). The females were followed until parturition in order to study the effect of omega 3 on their reproductive performance (fertility, prolificacy and stillbirth). Comparison of data between the six lots (Control puberts (CP), Control peripubertal (CPE), Linen grains pubertal (LGP), Linen grains peripubertal (LGPE), Fish oil puberts (FOP) and Fish oil peripubertal (FOPE)) for parameters of born deaths (BD), fertility and stillbirth rates showed no significant difference (P&gt;0.05). Whereas for total births (TB), live births (LB) and weaner births (WB), the differences are significant (P0.05). A very marked improvement in prolificity has been achieved by the incorporation of fish oil and flaxseed into the feed of the rabbits. In fact, the females of these two lots recorded the highest values (10.37 TB, 9.87LB, 9.3 WB and 10.44 TB, 9.77LB, 8.77WB respectively for FOPE and LGPE), as opposed to the unpunished rabbits of the control lot which gave the lowest numbers (7.14TB, 6.57LB and 6.57WB).

Periosteal incarceration versus interposition adipose tissue grafting in physeal fractures: pilot study in immature rabbits

PurposeThe purpose of this study is to evaluate bar formation following physeal fracture with incarcerated periosteum or adipose tissue graft using radiographic and histological methods in an immature rabbit model.MethodsTen-week-old rabbits underwent induced proximal tibia physeal fractures with a contralateral sham. Fractures had periosteum (n = 5) or adipose tissue (n = 5) interposed. Radiographs were compared over time by tibial medial-lateral side difference (TMLSD)(mm), femoral-tibial angle and tibia plateau angle, and physeal bars evidence. MicroCT was performed, growth plates reconstructed, and physeal area calculated and normalized to same animal contralateral physes. Physeal disruption and chondrocyte organization were evaluated histologically.ResultsRadiographic: After 6 weeks, physeal bars formed in both periosteum (4 of 4) and fat groups (3 of 5). The periosteum group showed a significant increase in the TMLSD between immediate post-op and 10 days later (p = 0.028); but, after 6 weeks, TMLSD change was not significantly different between the three groups (p = 0.161). MicroCT: The normalized physeal area of every physis in the fat group was more than 0.9 (0.99 ± 0.06). Only half of the periosteum group was over 0.9 (0.81 ± 0.24). Histology: Physeal disruption was seen by microscopic evaluation in none of the sham group, all 4 in the periosteum group and 4 of 5 in the fat group.ConclusionsFat interposition may prevent, or at least delay, the onset of bars across a fractured physis compared to periosteum, but it is not completely protective.

Dipyridamole-loaded 3D-printed bioceramic scaffolds stimulate pediatric bone regeneration in vivo without disruption of craniofacial growth through facial maturity

This study investigates a comprehensive model of bone regeneration capacity of dypiridamole-loaded 3D-printed bioceramic (DIPY-3DPBC) scaffolds composed of 100% beta-tricalcium phosphate (β –TCP) in an immature rabbit model through the time of facial maturity. The efficacy of this construct was compared to autologous bone graft, the clinical standard of care in pediatric craniofacial reconstruction, with attention paid to volume of regenerated bone by 3D reconstruction, histologic and mechanical properties of regenerated bone, and long-term safety regarding potential craniofacial growth restriction. Additionally, long-term degradation of scaffold constructs was evaluated. At 24 weeks in vivo, DIPY-3DPBC scaffolds demonstrated volumetrically significant osteogenic regeneration of calvarial and alveolar defects comparable to autogenous bone graft with favorable biodegradation of the bioactive ceramic component in vivo. Characterization of regenerated bone reveals osteogenesis of organized, vascularized bone with histologic and mechanical characteristics comparable to native bone. Radiographic and histologic analyses were consistent with patent craniofacial sutures. Lastly, through application of 3D morphometric facial surface analysis, our results support that DIPY-3DPBC scaffolds do not cause premature closure of sutures and preserve normal craniofacial growth. Based on this novel evaluation model, this DIPY-3DPBC scaffold strategy is a promising candidate as a safe, efficacious pediatric bone tissue engineering strategy.

In Vivo Response of Growth Plate to Biodegradable Mg-Ca-Zn Alloys Depending on the Surface Modification

Because Mg-Ca-Zn alloys are biodegradable and obviate secondary implant removal, they are especially beneficial for pediatric patients. We examined the degradation performance of Mg-Ca-Zn alloys depending on the surface modification and investigated the in vivo effects on the growth plate in a skeletally immature rabbit model. Either plasma electrolyte oxidation (PEO)-coated (n = 18) or non-coated (n = 18) Mg-Ca-Zn alloy was inserted at the distal femoral physis. We measured the degradation performance and femoral segment lengths using micro-CT. In addition, we analyzed the histomorphometric and histopathologic characteristics of the growth plate. Although there were no acute, chronic inflammatory reactions in either group, they differed significantly in the tissue reactions to their degradation performance and physeal responses. Compared to non-coated alloys, PEO-coated alloys degraded significantly slowly with diminished hydrogen gas formation. Depending on the degradation rate, large bone bridge formation and premature physeal arrest occurred primarily in the non-coated group, whereas only a small-sized bone bridge formed in the PEO-coated group. This difference ultimately led to significant shortening of the femoral segment in the non-coated group. This study suggests that optimal degradation could be achieved with PEO-coated Mg-Ca-Zn alloys, making them promising and safe biodegradable materials with no growth plate damage.