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1.
Cureus ; 16(3): e57121, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38681410

ABSTRACT

Introduction Research is an important aspect of residency and fellowship programs across the country. Developing strategies to foster research productivity is worthwhile. An annual research project is one strategy that some programs implement. Methods All resident and fellow (Sports Medicine, Adult Reconstruction, Spine) presentations at an orthopedic surgery department's annual research symposium from June 2016 through June 2021 were identified. Abstract titles, title keywords, and author names were searched in PubMed and Google Scholar to identify the presence of a peer-reviewed publication. Using the total number of research symposium presentations given, the publication rate was calculated for each year, as well as collectively for 2016 to 2021. In addition to publication rate, first author percent, number of citations, Altmetric score, and journal impact factor were recorded. Current PGY-2 through PGY-5 residents completed a survey to assess the perceived value of the annual research symposium. Results Ninety-eight research symposium presentations were reviewed (69 residents, 29 fellows). Forty (58%) resident studies were published and 28 were first-author publications (70%). Thirteen (45%) fellow studies were published and seven were first-author publications (54%). Combining residents and fellows, the overall publication rate was 54% (53/98), and 66% of these (35/53) were first-author publications. There was a wide range of published manuscript journal impact factors, Altmetric scores, and number of citations. All residents surveyed reported finding value in the research symposium. Conclusion The overall publication rate of presentations at an annual orthopedic surgery department research symposium between 2016 and 2021 was 54%, consistent with publication rates reported at National Orthopedic Surgery Society meetings. All residents reported finding value in the annual research symposium. The results of this study support the academic value of implementing a required annual research project and may provide a useful gauge to inform residency and fellowship curricula at other institutions.

2.
ACS Biomater Sci Eng ; 10(3): 1646-1660, 2024 03 11.
Article in English | MEDLINE | ID: mdl-38350651

ABSTRACT

Osteosarcoma (OS) is the most common primary malignant bone tumor, and the current standard of care for OS includes neoadjuvant chemotherapy, followed by an R0 surgical resection of the primary tumor, and then postsurgical adjuvant chemotherapy. Bone reconstruction following OS resection is particularly challenging due to the size of the bone voids and because patients are treated with adjuvant and neoadjuvant systemic chemotherapy, which theoretically could impact bone formation. We hypothesized that an osteogenic material could be used in order to induce bone regeneration when adjuvant or neoadjuvant chemotherapy is given. We utilized a biomimetic, biodegradable magnesium-doped hydroxyapatite/type I collagen composite material (MHA/Coll) to promote bone regeneration in the presence of systemic chemotherapy in a murine critical size defect model. We found that in the presence of neoadjuvant or adjuvant chemotherapy, MHA/Coll is able to enhance and increase bone formation in a murine critical size defect model (11.16 ± 2.55 or 13.80 ± 3.18 versus 8.70 ± 0.81 mm3) for pre-op cisplatin + MHA/Coll (p-value = 0.1639) and MHA/Coll + post-op cisplatin (p-value = 0.1538), respectively, at 12 weeks. These findings indicate that neoadjuvant and adjuvant chemotherapy will not affect the ability of a biomimetic scaffold to regenerate bone to repair bone voids in OS patients. This preliminary data demonstrates that bone regeneration can occur in the presence of chemotherapy, suggesting that there may not be a necessity to modify the current standard of care concerning neoadjuvant and adjuvant chemotherapy for the treatment of metastatic sites or micrometastases.


Subject(s)
Bone Neoplasms , Osteosarcoma , Humans , Animals , Mice , Cisplatin/pharmacology , Cisplatin/therapeutic use , Disease Models, Animal , Osteosarcoma/drug therapy , Bone Regeneration , Bone Neoplasms/drug therapy , Bone Neoplasms/pathology , Bone Neoplasms/surgery
3.
Sci Rep ; 13(1): 15323, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37714920

ABSTRACT

The effect of the mechanical micro-environment on spinal cord injury (SCI) and treatment effectiveness remains unclear. Currently, there are limited imaging methods that can directly assess the localized mechanical behavior of spinal cords in vivo. In this study, we apply new ultrasound elastography (USE) techniques to assess SCI in vivo at the site of the injury and at the time of one week post injury, in a rabbit animal model. Eleven rabbits underwent laminectomy procedures. Among them, spinal cords of five rabbits were injured during the procedure. The other six rabbits were used as control. Two neurological statuses were achieved: non-paralysis and paralysis. Ultrasound data were collected one week post-surgery and processed to compute strain ratios. Histologic analysis, mechanical testing, magnetic resonance imaging (MRI), computerized tomography and MRI diffusion tensor imaging (DTI) were performed to validate USE results. Strain ratios computed via USE were found to be significantly different in paralyzed versus non-paralyzed rabbits. The myelomalacia histologic score and spinal cord Young's modulus evaluated in selected animals were in good qualitative agreement with USE assessment. It is feasible to use USE to assess changes in the spinal cord of the presented animal model. In the future, with more experimental data available, USE may provide new quantitative tools for improving SCI diagnosis and prognosis.


Subject(s)
Elasticity Imaging Techniques , Lagomorpha , Spinal Cord Injuries , Animals , Rabbits , Diffusion Tensor Imaging , Spinal Cord Injuries/diagnostic imaging
4.
Osteoarthr Cartil Open ; 4(2): 100259, 2022 Jun.
Article in English | MEDLINE | ID: mdl-36475290

ABSTRACT

Objective: To demonstrate an ultra-high field (UHF) 7 â€‹T delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) protocol for quantitative post-traumatic osteoarthritis (PTOA) detection and monitoring in a rabbit anterior cruciate ligament transection (ACLT) model. Design: ACL transections were performed unilaterally in 5 rabbits (33-weeks-old, 3.5 â€‹± â€‹0.5 â€‹kg) to induce PTOA. MRI exams were performed at 7 â€‹T prior to and 2, 4, 7 and 10-weeks after ACLT using a modified dGEMRIC protocol. Voxel-based T1 and T2 maps were created over manually drawn femoral cartilage ROIs from the center of the tibial plateau to the posterior meniscus. Femoral, tibial, and patellar epiphyses were harvested 10-weeks post-surgery and processed for µCT imaging and histology. Results: Quantitative analysis revealed a 35% and 39% decrease in dGEMRIC index in the medial ACLT knee compartment 7- and 10-weeks post-surgery, respectively (p â€‹= â€‹0.009 and p â€‹= â€‹0.006) when compared to baseline. There was no significant change in the lateral ACLT compartment or in either compartment of the control knees. Visual inspection of histology confirmed PTOA in the ACLT knees. Osteophytes were found only in ACLT knees (osteophyte volume in femur: 94.53 â€‹± â€‹44.08 â€‹mm3, tibia: 29.35 â€‹± â€‹13.79 â€‹mm3, and patella: 3.84 â€‹± â€‹0.92 â€‹mm3) and were significantly larger in the medial compartments of the femur than lateral (p â€‹= â€‹0.0312). Conclusion: The dGEMRIC technique quantitatively applied at 7 â€‹T UHF-MRI demonstrates site-specific cartilage degeneration in a large animal PTOA model. This should encourage further investigation, with potential applications in drug and therapeutic animal trials as well as human studies.

5.
J Tissue Eng ; 13: 20417314221138945, 2022.
Article in English | MEDLINE | ID: mdl-36451687

ABSTRACT

Osteosarcoma (OS) is the most common bone tumor in pediatrics. After resection, allografts or metal endoprostheses reconstruct bone voids, and systemic chemotherapy is used to prevent recurrence. This urges the development of novel treatment options for the regeneration of bone after excision. We utilized a previously developed biomimetic, biodegradable magnesium-doped hydroxyapatite/type I collagen composite material (MHA/Coll) to promote bone regeneration in the presence of chemotherapy. We also performed experiments to determine if human mesenchymal stem cells (hMSCs) seeded on MHA/Coll scaffold migrate less toward OS cells, suggesting that hMSCs will not contribute to tumor growth and therefore the potential of oncologic safety in vitro. Also, hMSCs seeded on MHA/Coll had increased expression of osteogenic genes (BGLAP, SPP1, ALP) compared to hMSCs in the 2D condition, even when exposed to chemotherapeutics. This is the first study to demonstrate that a highly osteogenic scaffold can potentially be oncologically safe because hMSCs on MHA/Coll tend to differentiate and lose the ability to migrate toward tumor cells. Therefore, hMSCs on MHA/Coll could potentially be utilized for bone regeneration after OS excision.

6.
Stem Cells Dev ; 31(21-22): 672-683, 2022 11.
Article in English | MEDLINE | ID: mdl-36039931

ABSTRACT

Due to their immunosuppressive potential and ability to differentiate into multiple musculoskeletal cell lineages, mesenchymal stromal cells (MSCs) became popular in clinical trials for the treatment of musculoskeletal disorders. The aim of this study was to isolate and characterize native populations of MSCs from human cortical and cancellous bone from the posterior elements of the lumbar spine and determine what source of MSCs yields better quality and quantity of cells to be potentially used for spinal fusion repair. We were able to show that MSCs from trabecular and cortical spine had the typical MSC morphology and expression markers; the ability to differentiate in adipocyte, chondrocyte, or osteoblast but they did not have a consistent pattern in the expression of the specific differentiation lineage genes. Moreover, MSCs from both sites demonstrated an immune suppression profile suggesting that these cells may have a more promising success in applications related to immunomodulation more than exploring their ability to drive osteogenesis to prevent nonunion in spine fusion procedures.


Subject(s)
Mesenchymal Stem Cells , Humans , Osteogenesis , Cell Differentiation , Osteoblasts , Cell Lineage , Cells, Cultured
7.
J Surg Educ ; 79(4): 1063-1075, 2022.
Article in English | MEDLINE | ID: mdl-35232692

ABSTRACT

OBJECTIVE: The purpose of this study was to determine the strength of the association between medical school ranking and orthopedic surgery residency ranking using the current cohort of orthopedic surgery residents. DESIGN: We obtained a list of accredited programs from Doximity for orthopedic surgery residency programs and U.S. News & World Report for medical schools. Each orthopedic surgery residency program webpage was evaluated for the presence of an orthopedic surgery residency roster. For each resident, the medical school attended, allopathic or osteopathic degree, and year of post-graduate training was recorded. Orthopedic surgery residency programs and medical schools were assigned to one of four tiers for each based on their respective ranking. Descriptive statistics, Chi squared tests and Pearson residuals were used to analyze the association of orthopedic surgery residency tier and medical school tier. Post-hoc pairwise comparisons were performed utilizing the Bonferroni correction to account for 16 tests, correcting the significance level to p = 0.003. SETTING: 187 orthopedic surgery residency program webpages. PARTICIPANTS: 4123 orthopedic surgery residents. RESULTS: There was a significant association between medical school tier and orthopedic surgery residency tier (X2 [9] = 1214.78, p < 0.001). The post-hoc residual values were statistically significant for 75% (12/16) of tests performed. The majority of Tier 1 orthopedic surgery residents 50.5% (800/1585) attended a Tier 1 medical school. The strongest positive association exists between Tier 1 medical students attending Tier 1 residencies (residual = 23.978, p < 0.001). The strongest negative association with Tier 4 residencies was with Tier 1 medical schools (residual= -15.656, p< 0.001). CONCLUSIONS: Medical school ranking is an important consideration for prospective orthopedic surgery applicants and may become more important with less objective measures of academic performance such as United States Medical Licensing Examination Step 1. LEVEL OF EVIDENCE: Observational.


Subject(s)
Internship and Residency , Orthopedic Procedures , Orthopedics , Humans , Orthopedics/education , Prospective Studies , Schools, Medical , United States
8.
Clin Spine Surg ; 35(5): 213-221, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35239288

ABSTRACT

STUDY DESIGN: Systematic review. OBJECTIVE: This systematic review compares radiographic and clinical outcomes between instrumented and noninstrumented posterolateral lumbar spine fusions for the treatment of degenerative lumbar spondylolisthesis. SUMMARY OF BACKGROUND DATA: The optimal method of fusion for instability from degenerative lumbar spondylolisthesis remains to be an area of debate amongst spine surgeons. There are no prior comprehensive systematic review of comparative studies that compares outcomes between instrumented and noninstrumented posterolateral spine fusions for the treatment of degenerative lumbar spondylolisthesis. MATERIALS AND METHODS: A systematic review was registered with PROSPERO and performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using the PubMed, SCOPUS, and Ovid MEDLINE databases. All level I-III comparative studies published in the English language investigating the clinical outcomes between instrumented and noninstrumented posterolateral spine fusions for the treatment of degenerative lumbar spondylolisthesis were included. RESULTS: Seven studies (672 patients, 274 noninstrumented, 398 instrumented) were analyzed. One randomized study was level I evidence, 2 randomized studies were level II, and 4 nonrandomized studies were level III. Mean follow-up ranged from 1.4 to 5.9 years. Instrumented patients had a higher rate of solid fusion (87.6% vs. 77.1%, P=0.023) and a lower rate of definitive pseudarthrosis (5.3% vs. 19.9%, P<0.001). However, there was no difference in overall functional improvement at final follow-up between the 2 treatment groups (75.0% vs. 81.7%, P=0.258). In addition, there was no difference in reoperation or complication rates. CONCLUSIONS: For the treatment of degenerative lumbar spondylolisthesis, there are significantly higher rates of fusion among patients undergoing instrumented posterolateral fusion compared with noninstrumented posterolateral fusion. However, there is no difference in overall functional improvement, pain-related outcome scores, reoperation rates, or complication rates between the 2 treatment groups. LEVEL OF EVIDENCE: Level III-systematic review of level I-III studies.


Subject(s)
Spinal Fusion , Spondylolisthesis , Humans , Lumbar Vertebrae/surgery , Lumbosacral Region/surgery , Spinal Fusion/methods , Spondylolisthesis/diagnostic imaging , Spondylolisthesis/surgery , Treatment Outcome
9.
Front Bioeng Biotechnol ; 9: 622099, 2021.
Article in English | MEDLINE | ID: mdl-34485251

ABSTRACT

Remodeling of the human bony skeleton is constantly occurring with up to 10% annual bone volume turnover from osteoclastic and osteoblastic activity. A shift toward resorption can result in osteoporosis and pathologic fractures, while a shift toward deposition is required after traumatic, or surgical injury. Spinal fusion represents one such state, requiring a substantial regenerative response to immobilize adjacent vertebrae through bony union. Autologous bone grafts were used extensively prior to the advent of advanced therapeutics incorporating exogenous growth factors and biomaterials. Besides cost constraints, these applications have demonstrated patient safety concerns. This study evaluated the regenerative ability of a nanostructured, magnesium-doped, hydroxyapatite/type I collagen scaffold (MHA/Coll) augmented by autologous platelet-rich plasma (PRP) in an orthotopic model of posterolateral lumbar spinal fusion. After bilateral decortication, rabbits received either the scaffold alone (Group 1) or scaffold with PRP (Group 2) to the anatomic right side. Bone regeneration and fusion success compared to internal control were assessed by DynaCT with 3-D reconstruction at 2, 4, and 6 weeks postoperatively followed by comparative osteogenic gene expression and representative histopathology. Both groups formed significantly more new bone volume than control, and Group 2 subjects produced significantly more trabecular and cortical bone than Group 1 subjects. Successful fusion was seen in one Group 1 animal (12.5%) and 6/8 Group 2 animals (75%). This enhanced effect by autologous PRP treatment appears to occur via astounding upregulation of key osteogenic genes. Both groups demonstrated significant gene upregulation compared to vertebral bone controls for all genes. Group 1 averaged 2.21-fold upregulation of RUNX2 gene, 3.20-fold upregulation of SPARC gene, and 3.67-fold upregulation of SPP1 gene. Depending on anatomical subgroup (cranial, mid, caudal scaffold portions), Group 2 had significantly higher average expression of all genes than both control and Group 1-RUNX2 (8.23-19.74 fold), SPARC (18.67-55.44 fold), and SPP1 (46.09-90.65 fold). Our data collectively demonstrate the osteoinductive nature of a nanostructured MHA/Coll scaffold, a beneficial effect of augmentation with autologous PRP, and an ability to achieve clinical fusion when applied together in an orthotopic model. This has implications both for future study and biomedical innovation of bone-forming therapeutics.

10.
Med Image Anal ; 74: 102221, 2021 12.
Article in English | MEDLINE | ID: mdl-34520960

ABSTRACT

Three-dimensional (3-D) reconstruction of the spine surface is of strong clinical relevance for the diagnosis and prognosis of spine disorders and intra-operative image guidance. In this paper, we report a new technique to reconstruct lumbar spine surfaces in 3-D from non-invasive ultrasound (US) images acquired in free-hand mode. US images randomly sampled from in vivo scans of 9 rabbits were used to train a U-net convolutional neural network (CNN). More specifically, a late fusion (LF)-based U-net trained jointly on B-mode and shadow-enhanced B-mode images was generated by fusing two individual U-nets and expanding the set of trainable parameters to around twice the capacity of a basic U-net. This U-net was then applied to predict spine surface labels in in vivo images obtained from another rabbit, which were then used for 3-D spine surface reconstruction. The underlying pose of the transducer during the scan was estimated by registering stacks of US images to a geometrical model derived from corresponding CT data and used to align detected surface points. Final performance of the reconstruction method was assessed by computing the mean absolute error (MAE) between pairs of spine surface points detected from US and CT and by counting the total number of surface points detected from US. Comparison was made between the LF-based U-net and a previously developed phase symmetry (PS)-based method. Using the LF-based U-net, the averaged number of US surface points across the lumbar region increased by 21.61% and MAE reduced by 26.28% relative to the PS-based method. The overall MAE (in mm) was 0.24±0.29. Based on these results, we conclude that: 1) the proposed U-net can detect the spine posterior arch with low MAE and large number of US surface points and 2) the newly proposed reconstruction framework may complement and, under certain circumstances, be used without the aid of an external tracking system in intra-operative spine applications.


Subject(s)
Image Processing, Computer-Assisted , Neural Networks, Computer , Animals , Lumbar Vertebrae/diagnostic imaging , Rabbits , Ultrasonography
11.
J Tissue Eng Regen Med ; 15(7): 634-647, 2021 07.
Article in English | MEDLINE | ID: mdl-33880858

ABSTRACT

Incisional hernia is a common complication of hernia repair despite the development of various synthetic and bio-synthetic repair materials. Poor long-term mechanical strength, leading to high recurrence rates, has limited the use of acellular dermal matrices (ADMs) in ventral hernia repair (VHR). Biologically derived meshes have been an area of increasing interest. Still these materials bring the risk of more aggressive immune response and fibrosis in addition to the mechanical failures suffered by the synthetic materials. Platelet-rich plasma (PRP), a growth-factor-rich autologous blood product, has been shown to improve early neovascularization, tissue deposition, and to decrease the rates of recurrence. Here, we demonstrate that PRP promotes the release of growth factors stromal derived factor (SDF)-1, transforming growth factor-beta, and platelet-derived growth factor in a dose-dependent manner. Additionally, we utilize an aortic ring angiogenesis assay to show that PRP promotes angiogenesis in vitro. A rat model of VHR using StratticeTM ADM demonstrates similar findings in vivo, corresponding with the increased expression of vascular endothelial growth factor and collagen type 1 alpha 1. Finally, we show that the molecular and cellular activity initiated by PRP results in an increased mechanical stiffness of the hernia repair mesh over time. Collectively, these data represent an essential step in demonstrating the utility and the mechanism of platelet-derived plasma in biomaterial-aided wound healing and provide promising preclinical data that suggest such materials may improve surgical outcomes.


Subject(s)
Hernia, Ventral/surgery , Herniorrhaphy , Platelet-Rich Plasma/chemistry , Animals , Biomechanical Phenomena , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cross-Linking Reagents/pharmacology , Dermis/drug effects , Disease Models, Animal , Intercellular Signaling Peptides and Proteins/pharmacology , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Microvessels/drug effects , Myofibroblasts/cytology , Myofibroblasts/drug effects , Rats, Inbred Lew , Swine , Wound Healing/drug effects
12.
J Tissue Eng Regen Med ; 15(1): 3-13, 2021 01.
Article in English | MEDLINE | ID: mdl-33197147

ABSTRACT

The recurrence of ventral hernias continues to be a problem faced by surgeons, in spite of efforts toward implementing novel repair techniques and utilizing different materials to promote healing. Cadaveric acellular dermal matrices (Alloderm) have shown some promise in numerous surgical subspecialties, but these meshes still suffer from subsequent failure and necessitation of re-intervention. Here, it is demonstrated that the addition of platelet rich plasma to Alloderm meshes temporally modulates both the innate and cytotoxic inflammatory responses to the implanted material. This results in decreased inflammatory cytokine production at early time points, decreased matrix metalloproteinase expression, and decreased CD8+ T cell infiltration. Collectively, these immune effects result in a healing phenotype that is free from mesh thinning and characterized by increased material stiffness.


Subject(s)
Acellular Dermis , Biocompatible Materials , Collagen , Platelet-Rich Plasma , Rats, Inbred Lew , Surgical Mesh , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Collagen/chemistry , Collagen/immunology , Hernia, Ventral/immunology , Hernia, Ventral/surgery , Male , Platelet-Rich Plasma/chemistry , Platelet-Rich Plasma/immunology , Rats
13.
Cureus ; 12(7): e9045, 2020 Jul 07.
Article in English | MEDLINE | ID: mdl-32782864

ABSTRACT

Current studies evaluating the outcomes of an intradiscal injection of bone marrow concentrate (BMC) for lumbar disc degeneration are limited. The purpose of this review was to determine if an intradiscal injection of BMC for lumbar disc degeneration results in a statistically significant improvement in clinical outcomes. A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Levels I-IV investigations of intradiscal BMC injections in symptomatic lumbar disc degeneration were included in the analysis. Modified Coleman Methodology Scores (MCMS) were used to analyze study methodological quality. Only outcome measurements used by more than 50% of included studies, with a minimum follow-up of 12 months, were eligible for final data analysis. Pre-injection and post-injection visual analog scale (VAS) and Oswestry disability index (ODI) were compared using two-sample Z-tests. Seven articles (97 subjects (47 males, 38 females, 12 unspecified), mean age 33.9 ± 14.3 years, mean follow-up 44.4 ± 25.4 months) were analyzed. Six articles were level IV evidence and one article was level II. Mean MCMS was 56.6 ± 9.1. All subjects received single injections into the nucleus pulposus of one or more affected discs. VAS (66.0 mm to 20.9 mm; p<0.001) and ODI (44.4 to 19.1; p<0.001) significantly improved following the intradiscal BMC injection. One patient (1.0%) experienced herniated nucleus pulposus (HNP) following treatment. No other complications or re-injections were reported. In conclusion, despite our skepticism regarding the efficacy of the procedure, intradiscal injection of BMC for lumbar disc degeneration resulted in statistically significant improvement in VAS and ODI with low re-injection and complication rates in the studies assessed. Given that this study is limited to level IV evidence, the findings suggest that further randomized controlled studies may be worthwhile to evaluate the true efficacy of this treatment.

14.
Cureus ; 12(6): e8831, 2020 Jun 25.
Article in English | MEDLINE | ID: mdl-32607308

ABSTRACT

Current studies evaluating the outcomes of intradiscal platelet-rich plasma (PRP) injections in degenerative disc disease (DDD) are limited. The purpose of this review was to determine if an intradiscal injection of PRP for degenerative discs results in a statistically significant improvement in clinical outcomes. A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Level I-IV investigations of intradiscal PRP injections in DDD were sought in multiple databases. The Modified Coleman Methodology Score (MCMS) was used to analyze the methodological quality of the study. Only the outcome measurements used by more than 50% of the studies were included in the data analysis. The study heterogeneity and nature of evidence (mostly retrospective, non-comparative) precluded meta-analysis. Pre and post-injection pain visual analog scales (VAS) were compared using two sample Z-tests. Five articles (90 subjects, mean age 43.6 ± 7.7 years, mean follow-up 8.0 ± 3.6 months) were analyzed. Four articles were level IV evidence and one article was level II. Mean MCMS was 56.0 ± 10.3. There were 43 males and 37 females (10 unidentified). Pain VAS significantly improved following lumbar intradiscal PRP injection (69.7 mm to 43.3 mm; p<0.01). Two patients (2.2%) experienced lower extremity paresthesia after treatment. One patient (1.1%) underwent re-injection. No other complications were reported. In conclusion, intradiscal injection of PRP for degenerative discs resulted in statistically significant improvement in VAS with low re-injection and complication rates in this systematic review. It is unclear whether the improvements were clinically significant given the available evidence. The low level of evidence available (level IV) does not allow for valid conclusions regarding efficacy; however, the positive results suggest that further higher-quality studies might be of value.

15.
Pharmaceutics ; 12(2)2020 Feb 01.
Article in English | MEDLINE | ID: mdl-32024134

ABSTRACT

Bone morphogenetic protein-2 (BMP-2) has been demonstrated to be one of the most vital osteogenic factors for bone augmentation. However, its uncontrolled administration has been associated with catastrophic side effects, which compromised its clinical use. To overcome these limitations, we aimed at developing a safer controlled and sustained release of BMP-2, utilizing poly(lactic-co-glycolic acid)-multistage vector composite microspheres (PLGA-MSV). The loading and release of BMP-2 from PLGA-MSV and its osteogenic potential in vitro and in vivo was evaluated. BMP-2 in vitro release kinetics was assessed by ELISA assay. It was found that PLGA-MSV achieved a longer and sustained release of BMP-2. Cell cytotoxicity and differentiation were evaluated in vitro by MTT and alkaline phosphatase (ALP) activity assays, respectively, with rat mesenchymal stem cells. The MTT results confirmed that PLGA-MSVs were not toxic to cells. ALP test demonstrated that the bioactivity of BMP-2 released from the PLGA-MSV was preserved, as it allowed for the osteogenic differentiation of rat mesenchymal stem cells, in vitro. The biocompatible, biodegradable, and osteogenic PLGA-MSVs system could be an ideal candidate for the safe use of BMP-2 in orthopedic tissue engineering applications.

16.
SAGE Open Med ; 6: 2050312118761674, 2018.
Article in English | MEDLINE | ID: mdl-29568524

ABSTRACT

Intervertebral disc degeneration is a disease of the discs connecting adjoining vertebrae in which structural damage leads to loss of disc integrity. Degeneration of the disc can be a normal process of ageing, but can also be precipitated by other factors. Literature has made substantial progress in understanding the biological basis of intervertebral disc, which is reviewed here. Current medical and surgical management strategies have shortcomings that do not lend promise to be effective solutions in the coming years. With advances in understanding the cell biology and characteristics of the intervertebral disc at the molecular and cellular level that have been made, alternative strategies for addressing disc pathology can be discovered. A brief overview of the anatomic, cellular, and molecular structure of the intervertebral disc is provided as well as cellular and molecular pathophysiology surrounding intervertebral disc degeneration. Potential therapeutic strategies involving stem cell, protein, and genetic therapy for intervertebral disc degeneration are further discussed.

17.
Sci Rep ; 7(1): 17030, 2017 12 05.
Article in English | MEDLINE | ID: mdl-29208986

ABSTRACT

In mammals, tissue regeneration is accomplished through a well-regulated, complex cascade of events. The disruption of the cellular and molecular processes involved in tissue healing might lead to scar formation. Most tissue engineering approaches have tried to improve the regenerative outcome following an injury, through the combination of biocompatible materials, stem cells and bioactive factors. However, implanted materials can cause further healing impairments due to the persistent inflammatory stimuli that trigger the onset of chronic inflammation. Here, it is described at the molecular, cellular and tissue level, the body response to a functionalized biomimetic collagen scaffold. The grafting of chondroitin sulfate on the surface of the scaffold is able to induce a pro-regenerative environment at the site of a subcutaneous implant. The early in situ recruitment, and sustained local retention of anti-inflammatory macrophages significantly reduced the pro-inflammatory environment and triggered a different healing cascade, ultimately leading to collagen fibril re-organization, blood vessel formation, and scaffold integration with the surrounding native tissue.


Subject(s)
Biocompatible Materials/chemistry , Chondroitin Sulfates/chemistry , Collagen/chemistry , Macrophages/immunology , Regeneration , Tissue Engineering/methods , Tissue Scaffolds , Animals , Cells, Cultured , Cytokines , Macrophages/cytology , Macrophages/physiology , Rats , Rats, Inbred Lew , Wound Healing
18.
J Pain Res ; 10: 2047-2055, 2017.
Article in English | MEDLINE | ID: mdl-28894388

ABSTRACT

PURPOSE: The purpose of this study was to evaluate perioperative complications of lumbar discectomy with or without bone-anchored annular closure device (ACD) implant in patients at high risk of recurrent disc herniation. METHODS: This was a post hoc analysis of a randomized controlled trial that compared outcomes of lumbar discectomy with or without additional placement of an ACD. Patients presented with imaging evidence of lumbar disc herniation and radicular pain that was unresponsive to conservative care. Randomization occurred intraoperatively following discectomy completion and confirmation of annular defect width ≥6 mm. Main outcomes included serious adverse events (SAEs) from any cause, device- or procedure-related SAEs, and reoperations at the index level. The perioperative period included all outcomes occurring between the day of surgery and 90 days following hospital discharge. RESULTS: Analyses were performed on a modified intention-to-treat population consisting of 272 patients treated with ACD and 278 patients treated with lumbar discectomy only (controls). Mean patient age was 44 years, 59% were men, and mean body mass index was 26 kg/m2. Baseline patient characteristics and operative outcomes were comparable between groups. The risks of all-cause SAE (9.7% vs 16.3%, p=0.056), device- or procedure-related SAE (4.5% vs 10.2%, p=0.02), and index-level reoperation (1.9% vs 5.4%, p=0.03) were lower with ACD vs controls. In multivariable logistic regression, control group assignment and female gender were independently associated with higher risk of device- or procedure-related SAE and index-level reoperation, respectively. CONCLUSION: In patients undergoing lumbar discectomy to treat symptomatic intervertebral disc herniation, adjunctive placement of an ACD reduces the risk for perioperative complications occurring through 90 days following hospital discharge.

19.
J Surg Res ; 210: 244-252, 2017 04.
Article in English | MEDLINE | ID: mdl-28457335

ABSTRACT

BACKGROUND: To assess the integrity of hernia repair, imaging modalities such as computed tomography or ultrasound (US) are commonly used. Neither modality has currently the capacity to simultaneously image the mesh and quantify a prosthetic and surrounding tissue stiffness. In this pilot study, we hypothesize that US shear wave elastography (SWE) can be used to identify a polyester mesh and a biologic graft and to assess their stiffness noninvasively in a rat model of bridging hernia repair. METHODS: Lewis rats underwent hernia creation and repair with Parietex or Strattice at 30 d. After 3 mo, the animals were euthanized, and the Young's Modulus was measured using SWE. Three-dimensional reconstructions of the hernia pre- and post-repair were performed using in-house image processing algorithms. RESULTS: SWE was capable of accurate and real-time assessment and diagnosis of the hernia defects in vivo. Young's Modulus of Parietex meshes and Strattice grafts as estimated from the shear wave elastograms were found to be statistically different from each other (P < 0.05). Accurate three-dimensional reconstructions of the hernia defects pre- and post-repair were generated. CONCLUSIONS: In this study, we demonstrate the feasibility of using US SWE to detect ventral hernias and evaluate mesh repair in vivo. Our results indicate that the presence of a hernia and repair can be reliably visualized by SWE and three dimensionally reconstructed. Thus, this technique may provide both structural and functional information regarding the hernia and the repair.


Subject(s)
Elasticity Imaging Techniques/methods , Hernia, Ventral/diagnostic imaging , Herniorrhaphy/instrumentation , Incisional Hernia/diagnostic imaging , Surgical Mesh , Animals , Feasibility Studies , Hernia, Ventral/surgery , Incisional Hernia/surgery , Pilot Projects , Random Allocation , Rats , Rats, Inbred Lew , Treatment Outcome
20.
Wound Repair Regen ; 25(1): 98-108, 2017 01.
Article in English | MEDLINE | ID: mdl-28076885

ABSTRACT

The degree of cross-linking within acellular dermal matrices (ADM) seems to correlate to neovascularization when used in ventral hernia repair (VHR). Platelet-rich plasma (PRP) enhances wound healing through several mechanisms including neovascularization, but research regarding its effect on soft tissue healing in VHR is lacking. We sought to study the effect of cross-linking on PRP-induced neovascularization in a rodent model of bridging VHR. We hypothesized that ADM cross-linking would negatively affect PRP-induced neovessel formation. PRP was extracted and characterized from pooled whole blood. Porcine cross-linked (cADM) and non-cross-linked ADMs (ncADM) were implanted in a rat model of chronic VHR after treatment with saline (control) or PRP. Neovascularization of samples at 2, 4, and 6 weeks was assessed by hematoxylin and eosin and immunohistochemical staining of CD 31. Adhesion severity at necropsy was compared using a previously validated scale. Addition of PRP increased neovascularization in both cADM and ncADM at 2- and 4-week time points but appeared to do so in a dependent fashion, with significantly greater neovascularization in the PRP-treated ncADMs compared to cADMs. Omental adhesions were increased in all PRP-treated groups. Results indicate that, for 2-week measurements when compared with the cADM group without PRP therapy, the mean change in neovascularization due to ncADM was 3.27 (Z = 2.75, p = 0.006), PRP was 17.56 (Z = 14.77, p < 0.001), and the combined effect of ncADM and PRP was 9.41 (Z = 5.6, p < 0.001). The 4-week data indicate that the average neovascularization change due to ncADM was 0.676 (Z = 0.7, p = 0.484), PRP was 7.69 (Z = 7.95, p < 0.001), and combined effect of ncADM and PRP was 5.28 (Z = 3.86, p < 0.001). These findings validate PRP as a clinical adjunct to enhance the native tissue response to implantable biomaterials and suggest that ncADM is more amenable than cADM to induced neovascularization. PRP use could be advantageous in patients undergoing VHR where poor incorporation is anticipated and early-enhanced neovascularization is desired.


Subject(s)
Acellular Dermis , Hernia, Ventral/surgery , Herniorrhaphy , Neovascularization, Physiologic/physiology , Platelet-Rich Plasma/physiology , Wound Healing/physiology , Animals , Biocompatible Materials , Hernia, Ventral/physiopathology , Rats , Swine
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