Characterization of ventral incisional hernia and repair using shear wave elastography.

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.

Platelet-rich plasma: a biomimetic approach to enhancement of surgical wound healing.

Platelets are small anucleate cytoplasmic cell bodies released by megakaryocytes in response to various physiologic triggers. Traditionally thought to be solely involved in the mechanisms of hemostasis, platelets have gained much attention due to their involvement wound healing, immunomodulation, and antiseptic properties. As the field of surgery continues to evolve so does the need for therapies to aid in treating the increasingly complex patients seen. With over 14 million obstetric, musculoskeletal, and urological and gastrointestinal surgeries performed annually, the healing of surgical wounds continues to be of upmost importance to the surgeon and patient. Platelet-rich plasma, or platelet concentrate, has emerged as a possible adjuvant therapy to aid in the healing of surgical wounds and injuries. In this review, we will discuss the wound healing properties of platelet-rich plasma and various surgical applications.

Cross-linking of porcine acellular dermal matrices negatively affects induced neovessel formation using platelet-rich plasma in a rat model of hernia repair.

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.

Increased use of surgical energy promotes methicillin-resistant Staphylococcus aureus colonization in rabbits following open ventral hernia mesh repair.

BACKGROUND: Surgical energy has been widely implemented because of ease of use, effective hemostasis, and surgical dissection. Studies demonstrate its use to be an independent risk factor for postoperative wound infection. Methicillin-resistant Staphylococcus aureus (MRSA) is the most common bacteria found in postoperative mesh infection. No reports are available on the sequelae of surgical energy use for open ventral hernia repair (oVHR) with mesh. We hypothesized that increasing amounts of surgical energy will result in higher infectious burden after oVHR with composite multifilament polyester mesh (Parietex™ PCO). METHODS: New Zealand rabbits underwent bridging oVHR with Parietex™ PCO and were divided into three surgical treatment groups: (1) scalpel alone, (2) 120 J of energy, and (3) 600 J of energy. The bioprosthesis was then inoculated with 105 colony-forming units of MRSA. Rabbits were survived for 7 days with daily physical examination. Complete blood count, basci metabolic panel, and blood cultures were performed on postoperative days one, four, and seven. Surviving rabbits were killed, and meshes explanted for MRSA colony counts. RESULTS: Rabbits receiving the most surgical energy developed signs and symptoms of severe sepsis and wound necrosis within 24 h. In comparison, rabbits receiving no surgical energy had significantly less MRSA recovered from explanted mesh, significantly less bacteremia, and fewer adhesions. CONCLUSIONS: Increased use of surgical energy promoted greater colonization, exaggerated septic response to bacterial contamination, and more severe adhesions. In the absence of devitalized tissue, rabbits can effectively limit bacterial contamination. These findings support the surgical principles of proper tissue handling and highlight the detrimental effects of indiscriminant surgical energy usage, thus emphasizing the importance of programs such as Fundamental Use of Surgical Energy.

Biomimetic Concealing of PLGA Microspheres in a 3D Scaffold to Prevent Macrophage Uptake.

Scaffolds functionalized with delivery systems for the release of growth factors is a robust strategy to enhance tissue regeneration. However, after implantation, macrophages infiltrate the scaffold, eventually initiating the degradation and clearance of the delivery systems. Herein, it is hypothesized that fully embedding the poly(d,l-lactide-co-glycolide acid) microspheres (MS) in a highly structured collagen-based scaffold (concealing) can prevent their detection, preserving the integrity of the payload. Confocal laser microscopy reveals that non-embedded MS are easily internalized; when concealed, J774 and bone marrow-derived macrophages (BMDM) cannot detect them. This is further demonstrated by flow cytometry, as a tenfold decrease is found in the number of MS engulfed by the cells, suggesting that collagen can cloak the MS. This correlates with the amount of nitric oxide and tumor necrosis factor-α produced by J774 and BMDM in response to the concealed MS, comparable to that found for non-functionalized collagen scaffolds. Finally, the release kinetics of a reporter protein is preserved in the presence of macrophages, only when MS are concealed. The data provide detailed strategies for fabricating three dimensional (3D) biomimetic scaffolds able to conceal delivery systems and preserve the therapeutic molecules for release.

Platelet rich plasma enhances tissue incorporation of biologic mesh.

BACKGROUND: High recurrence rates because of poor tissue incorporation limit the use of acellular dermal matrices (ADMs) in ventral hernia repair (VHR). Platelet rich plasma (PRP) is a growth factor-rich autologous blood product known to enhance tissue repair through cellular proliferation and neovascularization. We sought to study the effect of PRP on a porcine noncross-linked ADM in an in vivo model of VHR. We hypothesized that PRP would enhance ADM-tissue incorporation in a rat model of VHR. METHODS: Whole blood was extracted from Lewis rats followed by PRP isolation and characterization. Using a rat model of VHR, a noncross-linked ADM (Strattice) was implanted and activated PRP applied before closure. Rats were sacrificed at 2, 4, and 6 wk. Immunohistochemical staining of CD 31 on endothelial cells was used to quantify neovascularization. Hematoxylin eosin stained tissues were measured to quantify tissue deposition. RESULTS: Platelet concentration of PRP was standardized to 1 × 10(6) platelets/µL. Grossly, vessels were more evident in PRP-treated rats. Immunohistochemical analysis demonstrated neovascularization was significantly greater in the PRP-treated ADMs at all time points. This increase in neovascularization correlated with an increased thickness of tissue deposition at 4 and 6 wk. CONCLUSIONS: PRP enhanced neovascularization and incorporation in a rat model of VHR. Enhanced neovascularization was associated with earlier and greater tissue deposition on the ADM. This suggests that PRP could be used as an adjunct to VHR in clinical scenarios where poor wound healing is anticipated and enhanced neovascularization and early tissue deposition are desired.

Endplate changes following discectomy: natural history and associations between imaging and clinical data.

PURPOSE: Some patients will experience post-operative back pain following lumbar discectomy, and the potential sources for that pain are poorly understood. One potential source is the vertebral endplates. The goal of this study was to document the changes that occur in lumbar endplates following discectomies, and to assess associations between endplate changes and clinical outcomes. METHODS: Changes in lumbar endplates and discs were assessed from X-rays, CT and MRI exams by comparing preoperative imaging with imaging obtained at yearly intervals up to 5 years. 260 endplates in 137 patients with single-level herniation and discectomy were analyzed. The geometry of osseous defects in the endplates was measured from the CT exams, and marrow and disc changes adjacent to endplates were assessed from the MRI exams. Clinical outcome assessments were collected at each time point. Descriptive statistics were used to describe endplate defect sizes, and logistic regression and analysis of variance were used to identify potential associations between endplate and vertebral body changes and clinical outcomes. RESULTS: Approximately 14 % of the endplates had osseous defects prior to surgery. After surgery, 24 % of inferior and 43 % of superior endplates had defects. Change occurred within the first year and remained relatively constant over the next few years. Disc signal intensity worsened and disc height decreased following surgery. New Modic changes were also observed. None of these changes were associated with having achieved a clinically significant improvement in outcome scores. The follow-up rates were low at the later time points and significant associations cannot be ruled out. CONCLUSIONS: This study documents lesion characteristics in detail and supports that osseous defects in the endplates at the level of a lumbar discectomy may be a relatively common finding following surgery, along with disc height loss, loss of disc signal intensity, and Modic changes. The clinical significance of these imaging findings could not be conclusively determined in this study.

Multiscale patterning of a biomimetic scaffold integrated with composite microspheres.

The ideal scaffold for regenerative medicine should concurrently mimic the structure of the original tissue from the nano- up to the macroscale and recapitulate the biochemical composition of the extracellular matrix (ECM) in space and time. In this study, a multiscale approach is followed to selectively integrate different types of nanostructured composite microspheres loaded with reporter proteins, in a multi-compartment collagen scaffold. Through the preservation of the structural cues of the functionalized collagen scaffold at the nano- and microscale, its macroscopic features (pore size, porosity, and swelling) are not altered. Additionally, the spatial confinement of the microspheres allows the release of the reporter proteins in each of the layers of the scaffold. Finally, the staged and zero-order release kinetics enables the temporal biochemical patterning of the scaffold. The versatile manufacturing of each component of the scaffold results in the ability to customize it to better mimic the architecture and composition of the tissues and biological systems.

Publication Rates of Podium Presentations at an Annual Orthopedic Surgery Resident and Fellow Research Symposium.

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.

Instrumented Versus Noninstrumented Spinal Fusion for Degenerative Lumbar Spondylolisthesis: A Systematic Review.

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.

Comparison Between Cancellous Trabecular and Cortical Specimens from Human Lumbar Spine Samples as an Alternative Source of Mesenchymal Stromal Cells.

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.

Analysis of Current Orthopedic Surgery Residents and Their Prior Medical Education: Does Medical School Ranking Matter in Orthopedic Surgery Match?

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.

Quantitative high-resolution 7T MRI to assess longitudinal changes in articular cartilage after anterior cruciate ligament injury in a rabbit model of post-traumatic osteoarthritis.

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.

Improved Posterolateral Lumbar Spinal Fusion Using a Biomimetic, Nanocomposite Scaffold Augmented by Autologous Platelet-Rich Plasma.

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.

Platelet-rich plasma enhances mechanical strength of strattice in rat model of ventral hernia repair.

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.

Addition of platelet-rich plasma supports immune modulation and improved mechanical integrity in Alloderm mesh for ventral hernia repair in a rat model.

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.

Systematic Review: Is Intradiscal Injection of Bone Marrow Concentrate for Lumbar Disc Degeneration Effective?

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.

Systemic Review: Is an Intradiscal Injection of Platelet-Rich Plasma for Lumbar Disc Degeneration Effective?

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.

Biocompatible PLGA-Mesoporous Silicon Microspheres for the Controlled Release of BMP-2 for Bone Augmentation.

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.

Randomized trials and registries: a computer simulation to study the impact of surgeon/patient factors on outcomes.

BACKGROUND CONTEXT: Patient factors (diabetes, osteoporosis, cardiopulmonary problems, previous surgery, smoking, worker's compensation, litigation) and surgeon factors (operative experience, patient selection, technical skill, setting) are known to significantly impact outcomes of spinal surgery. The impact of these factors is difficult to assess clinically given the volume of patients required to obtain statistically significant information, the costs involved, and ethical/equipoise considerations. Computer simulation offers a viable and useful alternative. PURPOSE: To establish a computer simulation for randomized trials (randomized controlled clinical trials)/registries and to examine the impact of surgeon and patient factors on surgical outcomes. STUDY DESIGN: Computer simulation of randomized controlled trials and nonrandomized trials (registries). METHODS: On the basis of an extensive review of the literature regarding surgical outcomes (lumbar disectomy and decompression) and patient/surgeon factors affecting such outcomes, hazard functions were developed to model the distribution of relative outcome as a function of the risk profile of individual patients and surgeons. An iterative algorithm was used to randomly or nonrandomly pair patients and surgeons to create simulated randomized controlled clinical trials/registries encompassing 10,000 performed procedures per run. RESULTS: When fully randomized, outcomes were as expected with 80% of patients obtaining a satisfactory result. When the best surgeons were paired with the best patients, success rates approached 98%; and when the worst surgeons were paired with the worst patients, success rates dropped to 53%. Other nonrandom combinations were also assessed. CONCLUSIONS: The computer simulation obtains expected outcomes for randomized controlled clinical trials and closely mirrors the range of outcomes seen in available case-series/registry data--a very useful model allowing assessment of the impact of patient/surgeon factors on surgical outcomes. Multiple patient/surgeon combinations are assessed and the implications of findings discussed.