RESUMO
Persistent local oxygen delivery is crucial to create a microenvironment for cell survival and nerve regeneration in acute spinal cord injury (SCI). This study aimed to fabricate calcium peroxide-based microspheres incorporated into a 3-D construct scaffold as a novel oxygen release therapy for SCI. The scaffolds were able to generate oxygen over the course of 21 days when incubated under hypoxic conditions. In vitro, GFP-labeled bone marrow-derived mesenchymal stem cells (MSCs) were planted into the scaffolds. We observed that scaffolds could enhance MSC survival under hypoxic conditions for more than 21 days. Oxygen generating scaffolds were transplanted into spinal cord injury sites of rats in vivo. Twelve weeks following transplantation, cavity areas in the injury/graft site were significantly reduced due to tissue regeneration. Additionally, the oxygen generating scaffolds improved revascularization as observed through vWF immunostaining. A striking feature was the occurrence of nerve fiber regeneration in the lesion sites, which eventually led to significant locomotion recovery. The present results indicate that the oxygen generating scaffolds have the property of sustained local oxygen release, thus facilitating regeneration in injured spinal cords.
Assuntos
Materiais Revestidos Biocompatíveis , Regeneração Tecidual Guiada , Oxigênio/farmacocinética , Traumatismos da Medula Espinal/reabilitação , Alicerces Teciduais , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Feminino , Regeneração Tecidual Guiada/instrumentação , Regeneração Tecidual Guiada/métodos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Microesferas , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/fisiologia , Oxigênio/metabolismo , Oxigênio/farmacologia , Peróxidos/química , Peróxidos/farmacocinética , Peróxidos/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapia , Alicerces Teciduais/químicaRESUMO
BACKGROUND: To investigate the clinical and radiological results of short pedicle screw fixation and vertebroplasty in osteoporotic thoracolumbar severe burst fractures. METHODS: From September 2006 to August 2010, 19 consecutive patients sustained osteoporotic thoracolumbar severe burst fractures with or without neurologic deficit and were included in this prospective study. All patients underwent short pedicle screw fixation and vertebroplasty. Segmental kyphosis, AVBHr and PVBHr, and Canal compromise were calculated on radiographs pre-operatively, post-operative and at final follow up. VAS, ODI and SF-36 were calculated pre-operatively and at final follow up. RESULTS: Mean operative time was 70.8 min (range 60~100 min) and mean blood loss was 92 ml (range 60~160 ml). The mean duration of their hospital stay was 4.5 days (range 3-7 days). The operative incisions were healing well. Average follow up time was 40.1 months (range 24~72 months). The AVBHr was corrected from preoperative (48.1 ± 6.8) % to postoperative (94.1 ± 1.7) % (P < 0.001). The PVBHr was corrected from preoperative (62.7 ± 4.8) % to postoperative (92.8 ± 1.8) % (P < 0.001). Canal compromise was corrected from preoperative (37.3 ± 5.8) % to postoperative (5.9 ± 2.3) % (P < 0.001). The segmental kyphosis was corrected from preoperative (20.6 ± 5.3) degree to postoperative (2.0 ± 3.2) degree (P < 0.001). VAS scores were reduced from preoperative 7.21 ± 0.86 to 2.21 ± 0.98 at final follow up (P < 0.001). SF-36 Bodily pain was reduced from preoperative 75.31 ± 13.85 to 13.74 ± 13.24 at final follow up (P < 0.001), and SF-36 Role Physical was reduced from preoperative 59.21 ± 26.63 to 19.74 ± 22.94 at final follow up (P < 0.001). The ODI scores were reduced from preoperative 81.68 ± 4.44 to 15.37 ± 5.54 at final follow up (P < 0.001). All 4 patients with partial neurological deficit initially had improvement. Cement leakage was observed in 3 cases (two anterior to vertebral body and one into the disc without sequela). There were no instances of instrumentation failure and no patient had persistent postoperative back pain. CONCLUSIONS: Vertebroplasty and short pedicle screw fixation has the advantages of both radiographic and functional results for treating osteoporotic thoracolumbar severe burst fractures using a purely posterior approach.
Assuntos
Fixação Interna de Fraturas/métodos , Vértebras Lombares/cirurgia , Fraturas por Osteoporose/cirurgia , Parafusos Pediculares , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia , Vertebroplastia/métodos , Idoso , Cimentos Ósseos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Vértebras Lombares/lesões , Masculino , Duração da Cirurgia , Medição da Dor , Estudos Prospectivos , Vértebras Torácicas/lesõesRESUMO
Micelles are nanostructures developed via the spontaneous assembly of amphiphilic polymers in aqueous systems, which possess the advantages of high drug stability or active-ingredient solubilization, targeted transport, controlled release, high bioactivity, and stability. Polysaccharides have excellent water solubility, biocompatibility, and degradability, and can be modified to achieve a hydrophobic core to encapsulate hydrophobic drugs, improve drug biocompatibility, and achieve regulated delivery of the loaded drug. Micelles drug delivery systems based on polysaccharides and their derivatives show great potential in the biomedical field. This review discusses the principles of self-assembly of amphiphilic polymers and the formation of micelles; the preparation of amphiphilic polysaccharides is described in detail, and an overview of common polysaccharides and their modifications is provided. We focus on the review of strategies for encapsulating drugs in polysaccharide-derived polymer micelles (PDPMs) and building intelligent drug delivery systems. This review provides new research directions that will help promote future research and development of PDPMs in the field of drug carriers.
Assuntos
Micelas , Polímeros , Polímeros/química , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Polissacarídeos/químicaRESUMO
Serious orthopedic disorders resulting from myriad diseases and impairments continue to pose a considerable challenge to contemporary clinical care. Owing to its limited regenerative capacity, achieving complete bone tissue regeneration and complete functional restoration has proven challenging with existing treatments. By virtue of cellular regenerative and paracrine pathways, stem cells are extensively utilized in the restoration and regeneration of bone tissue; however, low survival and retention after transplantation severely limit their therapeutic effect. Meanwhile, biomolecule materials provide a delivery platform that improves stem cell survival, increases retention, and enhances therapeutic efficacy. In this review, we present the basic concepts of stem cells and extracellular vesicles from different sources, emphasizing the importance of using appropriate expansion methods and modification strategies. We then review different types of biomolecule materials, focusing on their design strategies. Moreover, we summarize several forms of biomaterial preparation and application strategies as well as current research on biomacromolecule materials loaded with stem cells and extracellular vesicles. Finally, we present the challenges currently impeding their clinical application for the treatment of orthopedic diseases. The article aims to provide researchers with new insights for subsequent investigations.