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1.
J Clin Med ; 13(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38592686

RESUMO

Background: Multisegmental pathologic autofusion occurs in patients with ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH). It may lead to reduced vertebral bone density due to stress shielding. Methods: This study aimed to determine the effects of autofusion on bone density by measuring Hounsfield units (HU) in the mobile and immobile spinal segments of patients with AS and DISH treated at a tertiary care center. The mean HU was calculated for five distinct regions-cranial adjacent mobile segment, cranial fused segment, mid-construct fused segment, caudal fused segment, and caudal adjacent mobile segment. Means for each region were compared using paired-sample t-tests. Multivariable regression was used to determine independent predictors of mid-fused segment HUs. Results: One hundred patients were included (mean age 76 ± 11 years, 74% male). The mean HU for the mid-construct fused segment (100, 95% CI [86, 113]) was significantly lower than both cranial and caudal fused segments (174 and 108, respectively; both p < 0.001), and cranial and caudal adjacent mobile segments (195 and 115, respectively; both p < 0.001). Multivariable regression showed the mid-construct HUs were predicted by history of smoking (-30 HU, p = 0.009). Conclusions: HUs were significantly reduced in the middle of long-segment autofusion, which was consistent with stress shielding. Such shielding may contribute to the diminution of vertebral bone integrity in AS/DISH patients and potentially increased fracture risk.

2.
J Biomed Mater Res A ; 112(10): 1803-1816, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38644548

RESUMO

Degenerative spinal pathology is a widespread medical issue, and spine fusion surgeries are frequently performed. In this study, we fabricated an injectable bioactive click chemistry polymer cement for use in spinal fusion and bone regrowth. Taking advantages of the bioorthogonal click reaction, this cement can be crosslinked by itself eliminating the addition of a toxic initiator or catalyst, nor any external energy sources like UV light or heat. Furthermore, nano-hydroxyapatite (nHA) and microspheres carrying recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human vascular endothelial growth factor (rhVEGF) were used to make the cement bioactive for vascular induction and osteointegration. After implantation into a rabbit posterolateral spinal fusion (PLF) model, the cement showed excellent induction of new bone formation and bridging bone, achieving results comparable to autograft control. This is largely due to the osteogenic properties of nano-hydroxyapatite (nHA) and the released rhBMP-2 and rhVEGF growth factors. Since the availability of autograft sources is limited in clinical settings, this injectable bioactive click chemistry cement may be a promising alternative for spine fusion applications in addressing various spinal conditions.


Assuntos
Cimentos Ósseos , Proteína Morfogenética Óssea 2 , Química Click , Fumaratos , Poliésteres , Polipropilenos , Fusão Vertebral , Fator A de Crescimento do Endotélio Vascular , Animais , Coelhos , Cimentos Ósseos/química , Cimentos Ósseos/farmacologia , Proteína Morfogenética Óssea 2/farmacologia , Proteína Morfogenética Óssea 2/administração & dosagem , Polipropilenos/química , Poliésteres/química , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fumaratos/química , Durapatita/química , Durapatita/farmacologia , Proteínas Recombinantes/farmacologia , Injeções , Materiais Biocompatíveis/química , Fator de Crescimento Transformador beta
3.
ACS Appl Bio Mater ; 7(4): 2450-2459, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38500414

RESUMO

Spinal injuries or diseases necessitate effective fusion solutions, and common clinical approaches involve autografts, allografts, and various bone matrix products, each with limitations. To address these challenges, we developed an innovative moldable click chemistry polymer cement that can be shaped by hand and self-cross-linked in situ for spinal fusion. This self-cross-linking cement, enabled by the bioorthogonal click reaction, excludes the need for toxic initiators or external energy sources. The bioactivity of the cement was promoted by incorporating nanohydroxyapatite and microspheres loaded with recombinant human bone morphogenetic protein-2 and vascular endothelial growth factor, fostering vascular induction and osteointegration. The release kinetics of growth factors, mechanical properties of the cement, and the ability of the scaffold to support in vitro cell proliferation and differentiation were evaluated. In a rabbit posterolateral spinal fusion model, the moldable cement exhibited remarkable induction of bone regeneration and effective bridging of spine vertebral bodies. This bioactive moldable click polymer cement therefore presents a promising biomaterial for spinal fusion augmentation, offering advantages in safety, ease of application, and enhanced bone regrowth.


Assuntos
Durapatita , Fusão Vertebral , Animais , Coelhos , Humanos , Durapatita/farmacologia , Fator A de Crescimento do Endotélio Vascular , Polímeros , Química Click
4.
J Orthop Res ; 42(9): 1974-1983, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38522018

RESUMO

Segmental bone defects, often clinically treated with nondegradable poly(methylmethacrylate) (PMMA) in multistage surgeries, present a significant clinical challenge. Our study investigated the efficacy of 3D printed biodegradable polycaprolactone fumarate (PCLF)/PCL spacers in a one-stage surgical intervention for these defects, focusing on early bone regeneration influenced by spacer porosities. We compared nonporous PCLF/PCL and PMMA spacers, conventionally molded into cylinders, with porous PCLF/PCL spacers, 3D printed to structurally mimic segmental defects in rat femurs for a 4-week implantation study. Histological analysis, including tissue staining and immunohistochemistry with bone-specific antibodies, was conducted for histomorphometry evaluation. The PCLF/PCL spacers demonstrated compressive properties within 6 ± 0.5 MPa (strength) and 140 ± 15 MPa (modulus). Both porous PCLF/PCL and Nonporous PMMA formed collagen-rich membranes (PCLF/PCL: 92% ± 1.3%, PMMA: 86% ± 1.5%) similar to those induced in the Masquelet technique, indicating PCLF/PCL's potential for one-stage healing. Immunohistochemistry confirmed biomarkers for tissue regeneration, underscoring PCLF/PCL's regenerative capabilities. This research highlights PCLF/PCL scaffolds' ability to induce membrane formation in critical-sized segmental bone defects, supporting their use in one-stage surgery. Both solid and porous PCLF/PCL spacers showed adequate compressive properties, with the porous variants exhibiting BMP-2 expression and woven bone formation, akin to clinical standard PMMA. Notably, the early ossification of the membrane into the pores of porous scaffolds suggests potential for bone interlocking and regeneration, potentially eliminating the need for a second surgery required for PMMA spacers. The biocompatibility and biodegradability of PCLF/PCL make them promising alternatives for treating critical bone defects, especially in vulnerable patient groups.


Assuntos
Poliésteres , Impressão Tridimensional , Alicerces Teciduais , Animais , Poliésteres/química , Ratos Sprague-Dawley , Regeneração Óssea/efeitos dos fármacos , Ratos , Masculino , Fumaratos/química , Fêmur/cirurgia , Porosidade , Implantes Absorvíveis , Polimetil Metacrilato
5.
World Neurosurg ; 185: e509-e515, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38373686

RESUMO

BACKGROUND: Long-segment instrumentation, such as Harrington rods, offloads vertebrae within the construct, which may result in significant stress shielding of the fused segments. The present study aimed to determine the effects of spinal fusion on bone density by measuring Hounsfield units (HUs) throughout the spine in patients with a history of Harrington rod fusion. METHODS: Patients with a history of Harrington rod fusion treated at a single academic institution were identified. Mean HUs were calculated at 5 spinal segments for each patient: cranial adjacent mobile segment, cranial fused segment, midconstruct fused segment, caudal fused segment, and caudal adjacent mobile segment. Mean HUs for each level were compared using a paired-sample t test, with statistical significance defined by P < 0.05. Hierarchic multiple regression, including age, gender, body mass index, and time since original fusion, was used to determine predictors of midfused segment HUs. RESULTS: One hundred patients were included (mean age, 55 ± 12 years; 62% female). Mean HUs for the midconstruct fused segment (110; 95% confidence interval [CI], 100-121) were significantly lower than both the cranial and caudal fused segments (150 and 118, respectively; both P < 0.05), as well as both the cranial and caudal adjacent mobile segments (210 and 130, respectively; both P < 0.001). Multivariable regression showed midconstruct HUs were predicted only by patient age (-2.6 HU/year; 95% CI, -3.4 to -1.9; P < 0.001) and time since original surgery (-1.4 HU/year; 95% CI, -2.6 to -0.2; P = 0.02). CONCLUSIONS: HUs were significantly decreased in the middle of previous long-segment fusion constructs, suggesting that multilevel fusion constructs lead to vertebral bone density loss within the construct, potentially from stress shielding.


Assuntos
Densidade Óssea , Fusão Vertebral , Humanos , Fusão Vertebral/métodos , Fusão Vertebral/instrumentação , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Idoso , Estudos Retrospectivos , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Vértebras Torácicas/diagnóstico por imagem
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