In-Brace versus Out-of-Brace Protocol for Radiographic Follow-Up of Patients with Idiopathic Scoliosis:A Retrospective Study

The purpose of this retrospective study was to compare two standardized protocols for radiological follow-up (in-brace versus out-of-brace radiographs) to study the rate of curve progression over time in surgically treated idiopathic scoliosis (IS) patients after failed brace treatment. In-brace radiographs have the advantage that proper fit of the brace and in-brace correction can be evaluated. However, detection of progression might theoretically be more difficult. Fifty-one IS patients that underwent surgical treatment after failed brace treatment were included. For 25 patients, follow-up radiographs were taken in-brace. For the other 26 patients, brace treatment was temporarily stopped before out-of-brace follow-up radiographs were taken. Both groups showed significant curve progression compared to baseline after a mean follow-up period of 3.4 years. The protocol with in-brace radiographs was noninferior regarding curve progression rate over time. The estimated monthly Cobb angle progression based on the mixed-effect model was 0.5 degrees in both groups. No interaction effect was found for time, and patients' baseline Cobb angle (p = 0.98), and for time and patients' initial in-brace correction (p = 0.32). The results of this study indicate that with both in-brace and out-of-brace protocols for radiographic follow-up, a similar rate of curve progression can be expected over time in IS patients with failed brace treatment

Educating Parents Improves Their Ability to Recognize Adolescent Idiopathic Scoliosis: A Diagnostic Accuracy Study

(1) In countries where scoliosis screening programs ended, the responsibility for detection shifted from healthcare professionals to parents. Since recognizing scoliosis is difficult for parents, more patients are presenting late. Increased awareness of scoliosis may favor earlier detection. This study examines the effect of educating parents to recognize scoliosis. (2) In this cross-sectional study a consecutive group of parents completed a digital assessment. They had to complete two identical series of fourteen cases (eight with scoliosis and six without). Each case displayed two photographs of the child’s back; one in standing position and one during forward-bending. Based on visual inspection, parents had to indicate if the child had to be referred to a physician. After assessing the first series, information was given on how to detect scoliosis. Subsequently, parents assessed the second series of cases. Sensitivity and specificity were calculated before and after education. (3) A total of 100 parents completed the assessment. The sensitivity to detect scoliosis was slightly but significantly higher after education (68.8% versus 74.0%; p = 0.002), while specificity was not (74.0% versus 74.8%; p = 0.457). (4) This study showed that educating parents improved their ability to recognize scoliosis without increasing the false positive referral rate. Although written instructions can bridge the gap with professional screening programs, the overall sensitivity in this study remained low. Therefore, education can improve the awareness and ability to detect scoliosis, but will not replace screening by professionals

Educating Parents Improves Their Ability to Recognize Adolescent Idiopathic Scoliosis: A Diagnostic Accuracy Study

(1) In countries where scoliosis screening programs ended, the responsibility for detection shifted from healthcare professionals to parents. Since recognizing scoliosis is difficult for parents, more patients are presenting late. Increased awareness of scoliosis may favor earlier detection. This study examines the effect of educating parents to recognize scoliosis. (2) In this cross-sectional study a consecutive group of parents completed a digital assessment. They had to complete two identical series of fourteen cases (eight with scoliosis and six without). Each case displayed two photographs of the child’s back; one in standing position and one during forward-bending. Based on visual inspection, parents had to indicate if the child had to be referred to a physician. After assessing the first series, information was given on how to detect scoliosis. Subsequently, parents assessed the second series of cases. Sensitivity and specificity were calculated before and after education. (3) A total of 100 parents completed the assessment. The sensitivity to detect scoliosis was slightly but significantly higher after education (68.8% versus 74.0%; p = 0.002), while specificity was not (74.0% versus 74.8%; p = 0.457). (4) This study showed that educating parents improved their ability to recognize scoliosis without increasing the false positive referral rate. Although written instructions can bridge the gap with professional screening programs, the overall sensitivity in this study remained low. Therefore, education can improve the awareness and ability to detect scoliosis, but will not replace screening by professionals

Are torso asymmetry and torso displacements in a computer brace model associated with initial in-brace correction in adolescent idiopathic scoliosis?

Abstract Background Lack of initial in-brace correction is strongly predictive for brace treatment failure in adolescent idiopathic scoliosis (AIS) patients. Computer-aided design (CAD) technology could be useful in quantifying the trunk in 3D and brace characteristics in order to further investigate the effect of brace modifications on initial in-brace correction and subsequently long-term brace treatment success. The purpose of this pilot study was to identify parameters obtained from 3D surface scans which influence the initial in-brace correction (IBC) in a Boston brace in patients with AIS. Methods Twenty-five AIS patients receiving a CAD-based Boston brace were included in this pilot study consisting of 11 patients with Lenke classification type 1 and 14 with type 5 curves. The degree of torso asymmetry and segmental peak positive and negative torso displacements were analyzed with the use of patients’ 3D surface scans and brace models for potential correlations with IBC. Results The mean IBC of the major curve on AP view was 15.9% (SD = 9.1%) for the Lenke type 1 curves, and 20.1% (SD = 13.9%) for the type 5 curves. The degree of torso asymmetry was weakly correlated with patient’s pre-brace major curve Cobb angle and negligible correlated with major curve IBC. Mostly weak or negligible correlations were observed between IBC and the twelve segmental peak displacements for both Lenke type 1 and 5 curves. Conclusion Based on the results of this pilot study, the degree of torso asymmetry and segmental peak torso displacements in the brace model alone are not clearly associated with IBC

In Vitro and In Vivo Correlation of BMP-2 Release Profiles from Complex Delivery Vehicles

Local sustained delivery of bioactive molecules from biomaterials is a promising strategy to enhance bone regeneration. To optimize delivery vehicles for bone formation, the design characteristics are tailored with consequential effect on BMP-2 release and bone regeneration. Complying with the 3R principles, the growth factor release is often investigated in vitro using several buffers to mimic the in vivo physiological environment. However, this remains an unmet need. Therefore, this study investigates the correlation between the in vitro and in vivo (IVIVC) BMP-2 release from complex delivery vehicles in several commonly used in vitro buffers: cell culture model, phosphate buffered saline, and a strong desorption buffer. The results from this study showed that the release environment affected the BMP-2 release profiles, creating distinct relationships between release versus time and differences in extent of release. According to the guidance set by the U.S. Food and Drug Administration (FDA), in vitro- in vivo correlation resulted in level A internal predictability for individual composites. Since the IVIVC was influenced by the BMP-2 loading method and composite surface chemistry, the external predictive value of the IVIVCs was limited. These results show that the IVIVCs can be used for predicting the release of an individual composite. However, the models cannot be used for predicting in vivo release for different composite formulations since they lack external predictability. Potential confounding effects of drug type, delivery vehicle formulations and application site should be added to the equation to develop one single IVIVC applicable for complex delivery vehicles. Altogether, these results imply that more sophisticated in vitro systems should be used in bone regeneration to accurately discriminate and predict in vivo BMP-2 release from different complex delivery vehicles

In Vitro and In Vivo Correlation of BMP-2 Release Profiles from Complex Delivery Vehicles

Local sustained delivery of bioactive molecules from biomaterials is a promising strategy to enhance bone regeneration. To optimize delivery vehicles for bone formation, the design characteristics are tailored with consequential effect on BMP-2 release and bone regeneration. Complying with the 3R principles, the growth factor release is often investigated in vitro using several buffers to mimic the in vivo physiological environment. However, this remains an unmet need. Therefore, this study investigates the correlation between the in vitro and in vivo (IVIVC) BMP-2 release from complex delivery vehicles in several commonly used in vitro buffers: cell culture model, phosphate buffered saline, and a strong desorption buffer. The results from this study showed that the release environment affected the BMP-2 release profiles, creating distinct relationships between release versus time and differences in extent of release. According to the guidance set by the U.S. Food and Drug Administration (FDA), in vitro- in vivo correlation resulted in level A internal predictability for individual composites. Since the IVIVC was influenced by the BMP-2 loading method and composite surface chemistry, the external predictive value of the IVIVCs was limited. These results show that the IVIVCs can be used for predicting the release of an individual composite. However, the models cannot be used for predicting in vivo release for different composite formulations since they lack external predictability. Potential confounding effects of drug type, delivery vehicle formulations and application site should be added to the equation to develop one single IVIVC applicable for complex delivery vehicles. Altogether, these results imply that more sophisticated in vitro systems should be used in bone regeneration to accurately discriminate and predict in vivo BMP-2 release from different complex delivery vehicles

Effect of biomaterial electrical charge on in vivo bone formation

Biomaterials that act as both protein delivery vehicle and scaffold, can improve the safety and efficacy of bone morphogenetic protein-2 (BMP-2) for clinical applications. However, the optimal scaffold characteristics are not known. The osteoinductive and osteoconductive capacity of a fixed electrically charged surface is thus far unexplored. Therefore, in this study we aim to investigate the effect of different electrical states on BMP-2 induced bone formation in oligo[(polyethylene glycol) fumarate] (OPF) hydrogels. Neutral, negatively or positively charged scaffolds were fabricated using unmodified OPF (neutral charge), sodium methacrylate (SMA) crosslinked OPF (negative charge), or [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAE) crosslinked OPF (positive charge), respectively. To allow investigation of surface charge for different BMP-2 release rates, three BMP-2 release profiles were generated by protein encapsulation into poly(lactic-co-glycolic acid) (PLGA) microspheres and/or adsorption on the OPF composite. Release of radiolabeled 125I-BMP-2 was analyzed in vitro and in vivo and bone formation was assessed after 9 weeks of subcutaneous implantation in rats. Negatively charged OPF generated significantly more bone formation compared to neutral and positively charged OPF. This effect was seen for all three loading methods and subsequent BMP-2 release profiles. Along with charge modifications, a more sustained release of BMP-2 improved bone formation in OPF composites. Overall, this study clearly shows that negative charge enhances bone formation compared to neutral and positive charge in OPF composites

Bone morphogenetic protein-2 release profile modulates bone formation in phosphorylated hydrogel

The optimal release profile of locally delivered BMP-2 for safe and effective clinical application is unknown. In this work, the effect of differential BMP-2 release on bone formation was investigated using a novel biomaterial oligo[(polyethylene glycol) fumarate] bis[2-(methacryloyloxy) ethyl] phosphate hydrogel (OPF-BP) containing poly(lactic-co-glycolic acid) microspheres. Three composite implants with same biomaterial chemistry and structure but different BMP-loading methods were created: BMP-2 encapsulated in microspheres (OPF-BP-Msp), BMP-2 encapsulated in microspheres and adsorbed on the phosphorylated hydrogel (OPF-BP-Cmb), and BMP-2 adsorbed on the phosphorylated hydrogel (OPF-BP-Ads). These composites were compared to the clinically used BMP-2 carrier, Infuse® absorbable collagen sponge (ACS). Differential release profiles of bioactive BMP-2 were achieved by these composites. In a rat subcutaneous implantation model, OPF-BP-Ads and ACS generated a large BMP-2 burst release (>75%), while a more sustained release was seen for OPF-BP-Msp and OPF-BP-Cmb (~25% and 50% burst, respectively). OPF-BP-Ads generated significantly more bone compared to all other composites, and the bone formation was 12-fold higher than the clinically used ACS. Overall, this study clearly shows that BMP-2 burst release generates more subcutaneous bone compared to sustained release in OPF-BP-microsphere composites. Furthermore, composites should not only function as a delivery vehicle but also provide a proper framework to achieve appropriate bone formation

Bone morphogenetic protein-2 release profile modulates bone formation in phosphorylated hydrogel

The optimal release profile of locally delivered BMP-2 for safe and effective clinical application is unknown. In this work, the effect of differential BMP-2 release on bone formation was investigated using a novel biomaterial oligo[(polyethylene glycol) fumarate] bis[2-(methacryloyloxy) ethyl] phosphate hydrogel (OPF-BP) containing poly(lactic-co-glycolic acid) microspheres. Three composite implants with same biomaterial chemistry and structure but different BMP-loading methods were created: BMP-2 encapsulated in microspheres (OPF-BP-Msp), BMP-2 encapsulated in microspheres and adsorbed on the phosphorylated hydrogel (OPF-BP-Cmb), and BMP-2 adsorbed on the phosphorylated hydrogel (OPF-BP-Ads). These composites were compared to the clinically used BMP-2 carrier, Infuse® absorbable collagen sponge (ACS). Differential release profiles of bioactive BMP-2 were achieved by these composites. In a rat subcutaneous implantation model, OPF-BP-Ads and ACS generated a large BMP-2 burst release (>75%), while a more sustained release was seen for OPF-BP-Msp and OPF-BP-Cmb (~25% and 50% burst, respectively). OPF-BP-Ads generated significantly more bone compared to all other composites, and the bone formation was 12-fold higher than the clinically used ACS. Overall, this study clearly shows that BMP-2 burst release generates more subcutaneous bone compared to sustained release in OPF-BP-microsphere composites. Furthermore, composites should not only function as a delivery vehicle but also provide a proper framework to achieve appropriate bone formation

Decellularized Cartilage-Derived Matrix as Substrate for Endochondral Bone Regeneration

Following an endochondral approach to bone regeneration, multipotent stromal cells (MSCs) can be cultured on a scaffold to create a cartilaginous callus that is subsequently remodeled into bone. An attractive scaffold material for cartilage regeneration that has recently regained attention is decellularized cartilage-derived matrix (CDM). Since this material has shown potential for cartilage regeneration, we hypothesized that CDM could be a potent material for endochondral bone regeneration. In addition, since decellularized matrices are known to harbor bioactive cues for tissue formation, we evaluated the need for seeded MSCs in CDM scaffolds. In this study, ectopic bone formation in rats was evaluated for CDM scaffolds seeded with human MSCs and compared with unseeded controls. The MSC-seeded samples were preconditioned in chondrogenic medium for 37 days. After 8 weeks of subcutaneous implantation, the extent of mineralization was significantly higher in the MSC-seeded constructs versus unseeded controls. The mineralized areas corresponded to bone formation with bone marrow cavities. In addition, rat-specific bone formation was confirmed by collagen type I immunohistochemistry. Finally, fluorochrome incorporation at 3 and 6 weeks revealed that the bone formation had an inwardly directed progression. Taken together, our results show that decellularized CDM is a promising biomaterial for endochondral bone regeneration when combined with MSCs at ectopic locations. Modification of current decellularization protocols may lead to enhanced functionality of CDM scaffolds, potentially offering the prospect of generation of cell-free off-the-shelf bone regenerative substitutes