Alberto Di Martino

Nucleus pulposus replacement: basic science and indications for clinical use.

Study Design. A critical review of available and emerging nucleus pulposus replacement implants. Objectives. To review the biomechanics, design, and clinical data of currently available and developing nucleus pulposus replacement technologies. Summary of Background Data. The interest in minimally invasive treatment of degenerative disc disease has grown as the technology for intervertebral motion-sparing devices continues to improve. Replacement of nucleus pulposus without anular obliteration represents a tempting alternative to spinal fusion procedures. The aim in nucleus pulposus replacement is to slow adjacent level degeneration, restore normal loads to the diseased level, and restore segmental spinal biomechanics. Methods. A literature review of currently available biomaterials, biomechanics, and available preclinical and clinical data on nucleus pulposus replacement implants. Results. New synthetic biomaterials have recently been developed to closely mimic native biomechanics during compressive loading cycles of the intervertebral disc. This, in conjunction with improved understanding of global spine biomechanics, has allowed the development of novel nucleus replacement implants. These implants are currently at different stages of preclinical and clinical investigations. Conclusions. Although some of the newly designed prosthesis have shown some promising results in preclinical studies, rigorous short- and long-term clinical evaluations will be critical in evaluating their true efficacy.

Toward an optimum system for intervertebral disc organ culture : TGF-β3 enhances nucleus pulposus and anulus fibrosus survival and function through modulation of TGF-β-R expression and ERK signaling

Study Design. Rat lumbar discs comprising nucleus pulposus, annulus fibrosus, and cartilaginous endplates were cultured for 1 week in a specialized media containing either TGF-β1 or TGF-β3. Role of TGF-β isoforms on cell function was evaluated. Objective. To develop an in vitro organ culture of rat intervertebral disc and evaluate effects of TGF-β3 on disc cell function. Summary of Background Data. An in vitro model system is of considerable value in understanding the cell biology of the intervertebral disc. Development of a useful organ culture model would enhance understanding of disc function in health and disease. Materials and Methods. Rat lumbar intervertebral discs were maintained in organ culture in media supplemented with TGF-β3 or TGF-β1 for 1 week. Tissue morphology was studied using routine histologic, histochemical and immunohistochemical techniques. Cell function was assessed by gene expression, sulfate incorporation, and Western blot analysis. Results. After 1 week in culture with TGF-β3 and TGF-β1, the gross morphology and tissue architecture of the disc were preserved. TUNEL analysis indicated that there was no evidence of cell death in the nucleus pulposus or the anulus fibrosus. The level of Alcian blue staining in the nucleus pulposus was similar to that of the freshly isolated disc. However, when compared with TGF-β1, TGF-β3 elevated the expression of critical matrix genes, enhanced [35S] incorporation into proteoglycans, preserved the expression of TGF-β receptors, and decreased aggrecan turnover. There was also increased activation (phosphorylation) of ERK, a critical signaling protein. Moreover, inhibition of ERK activity, in the presence TGF-β3, resulted in suppression of collagen Type II, aggrecan, TGF-β-RI, TGF-β-RII and TGF-β-RIII mRNA expression. Conclusions. TGF-β3 maintains the phenotype of disc cells in organ culture. It exerts this effect, in part, by elevating the levels of activated ERK1/2, which in turn regulates the expression of TGF-β-RI and TGF-β-RII.

Osteogenic potential of adult human stem cells of the lumbar vertebral body and the iliac crest.

Study Design. Marrow was aspirated from the vertebral body (VB) and iliac crest (IC) of patients undergoing lumbar spinal surgery, following an approved protocol. Progenitor cells were isolated using standard culture conditions and their osteogenic potential evaluated. Objective. To evaluate the osteogenic potential of mesenchymal stem cells (MSCs) isolated from the bone marrow of the human VB. Summary of Background Data. IC marrow grafting during cervical discectomy and fusion procedure is associated with donor site morbidity. Since the VB contains marrow cells, it may be possible to circumvent this problem by using this tissue for osseous graft supplementation. However, there is paucity of information concerning the osteogenic potential of non-IC-derived progenitor cells. Herein, we address this issue. Methods. Marrow samples from VB of patients undergoing lumbar spinal surgery were collected; marrow was also harvested from the IC. Progenitor cells were isolated and the number of colony forming unit-fibroblastic (CFU-F) determined. The osteogenic potential of the cells was characterized using biochemical and molecular biology techniques. Results. Both the VB and IC marrow generated small, medium, and large sized CFU-F. Higher numbers of CFU-F were obtained from the VB marrow than the IC (P < 0.05). Progenitor cells from both anatomic sites expressed comparable levels of CD166, CD105, CD49a, and CD63. Moreover, progenitor cells from the VB exhibited an increased level of alkaline phosphatase activity. MSCs of the VB and the IC displayed similar levels of expression of Runx-2, collagen Type I, CD44, ALCAM, and ostecalcin. The level of expression of bone sialoprotein was higher in MSC from the IC than the VB. VB and IC cells mineralized their extracellular matrix to a similar extent. Conclusions. Our studies show that CFU-F frequency is higher in the marrow of the VB than the IC. Progenitor cells isolated from both sites respond in a similar manner to an osteogenic stimulus and express common immunophenotypes. Based on these findings, we propose that progenitor cells from the lumbar vertebral marrow would be suitable candidate for osseous graft supplementation in spinal fusion procedures. Studies must now be conducted using animal models to ascertain if cells of the VB are as effective as those of the IC for the fusion applications.

Fracture of Ceramic Bearing Surfaces following Total Hip Replacement: A Systematic Review

Ceramic bearing surfaces are increasingly used for total hip replacement, notwithstanding that concern is still related to ceramic brittleness and its possible mechanical failure. The aim of this systematic review is to answer three questions: (1) Are there risk factors for ceramic component fracture following total hip replacement? (2) Is it possible to perform an early diagnosis of ceramic component failure before catastrophic fracture occurs? (3) Is it possible to draw guidelines for revision surgery after ceramic components failure? A PubMed and Google Scholar search was performed and reference citations from publications identified in the literature search were reviewed. The use of 28 mm short-neck femoral head carries an increased risk of fracture. Acetabular component malposition might increase the risk of ceramic liner fractures. Synovial fluid microanalysis and CT scan are promising in early diagnosis of ceramic head and liner failure. Early revision is suggested in case of component failure; no consensus exists about the better coupling for revision surgery. Ceramic brittleness remains a major concern. Due to the increased number of ceramic on ceramic implants, more revision surgeries and reports on ceramic components failure are expected in the future. An algorithm of diagnosis and treatment for ceramic hip failure is proposed.

Electrospun scaffolds for bone tissue engineering.

Tissue engineering aims to regenerate native tissues and will represent the alternative choice of standard surgery for different kind of tissue damages. The fundamental basis of tissue engineering is the appropriate selection of scaffolds and their morphological, mechanical, chemical, and biomimetic properties, closely related to cell lines that will be seeded therein. The aim of this review is to summarize and report the innovative scientific contributions published in the field of orthopedic tissue engineering, in particular about bone tissue engineering. We have focused our attention on the electrospinning technique, as a scaffold fabrication method. Electrospun materials are being evaluated as scaffolds for bone tissue engineering, and the results of all these studies clearly indicate that they represent suitable potential substrates for cell-based technologies.

Intervertebral disc regeneration: from the degenerative cascade to molecular therapy and tissue engineering.

Low back pain is one of the major health problems in industrialized countries, as a leading source of disability in the working population. Intervertebral disc degeneration has been identified as its main cause, being a progressive process mainly characterized by alteration of extracellular matrix composition and water content. Many factors are involved in the degenerative cascade, such as anabolism/catabolism imbalance, reduction of nutrition supply and progressive cell loss. Currently available treatments are symptomatic, and surgical procedures consisting of disc removal are often necessary. Recent advances in our understanding of intervertebral disc biology led to an increased interest in the development of novel biological treatments aimed at disc regeneration. Growth factors, gene therapy, stem cell transplantation and biomaterials‐based tissue engineering might support intervertebral disc regeneration by overcoming the limitation of the self‐renewal mechanism. The aim of this paper is to overview the literature discussing the current status of our knowledge from the degenerative cascade of the intervertebral disc to the latest molecular, cell‐based therapies and tissue‐engineering strategies for disc regeneration. Copyright

Eosinophilic granuloma of the pediatric cervical spine.

Study Design. Retrospective case review of children with eosinophilic granuloma of the cervical spine. Objective. To present the clinical features, radiographic findings, management, and results of 7 pediatric patients with eosinophilic granuloma of the cervical spine. Summary of Background Data. Management of the eosinophilic granuloma of the pediatric cervical spine is challenging, and must be adapted according to the patient, as no level I evidences have been produced. The therapeutic goals in these children are spinal stability, preservation of neurologic function, and relief of pain, always keeping in mind that patients are still growing. The localization in the cervical spine of children is extremely rare, with less than 50 patients reported in literature between 1966 and 2008. Methods. We reviewed the 7 pediatric patients with a diagnosis of eosinophilic granuloma of the cervical spine who were managed between 1970 and 1990 by the senior author. All patients presented with isolated cervical spine involvement, and all of them had a histologic diagnosis of eosinophilic granuloma (EG). All had open physes. Results. There were 5 boys and 2 girls (mean age: 10 years; range 4–16). We followed-up patients for 19 years (range 8–29). The symptoms at presentation varied according to the localization of the tumor in the cervical spine. Conclusion. Management of pediatric patients with EG of the cervical spine is challenging, especially when there is neurologic involvement. Observation alone, prolonged immobilization, systemic chemotherapy, curettage with or without bone grafting, corticosteroid injection, and low dose radiation therapy have been proposed for the management of patients with EG. Surgery is required when the child presents neurologic involvement. Children who received a vertebral interbody fusion can show, at long period follow-up, normal shape of the neck, with maintenance of the normal motion of the adjacent segments.

Obesity as a Risk Factor for Tendinopathy: A Systematic Review

Purpose. In the last few years, evidence has emerged to support the possible association between increased BMI and susceptibility to some musculoskeletal diseases. We systematically review the literature to clarify whether obesity is a risk factor for the onset of tendinopathy. Methods. We searched PubMed, Cochrane Central, and Embase Biomedical databases using the keywords “obesity,” “overweight,” and “body mass index” linked in different combinations with the terms “tendinopathy,” “tendinitis,” “tendinosis,” “rotator cuff,” “epicondylitis,” “wrist,” “patellar,” “quadriceps,” “Achilles,” “Plantar Fascia,” and “tendon.” Results. Fifteen studies were included. No level I study on this subject was available, and the results provided are ambiguous. However, all the 5 level II studies report the association between obesity measured in terms of BMI and tendon conditions, with OR ranging between 1.9 (95% CI: 1.1–2.2) and 5.6 (1.9–16.6). Conclusions. The best evidence available to date indicates that obesity is a risk factor for tendinopathy. Nevertheless, further studies should be performed to establish the real strength of the association for each type of tendinopathy, especially because the design of the published studies does not allow identifying a precise cause-effect relationship and the specific role of obesity independently of other metabolic conditions.

Cervical Spine Surgery: An Historical Perspective

BackgroundContinued innovation in surgery requires a knowledge and understanding of historical advances with a recognition of successes and failures.Questions/purposesTo identify these successes and failures, we selectively reviewed historical literature on cervical spine surgery with respect to the development of (1) surgical approaches, (2) management of degenerative disc disease, and (3) methods to treat segmental instability.MethodsWe performed a nonsystematic review using the keywords “cervical spine surgery” and “history” and “instrumentation” and “fusion” in combination with “anterior approach” and “posterior approach,” with no limit regarding the year of publication. Used databases were PubMed and Google Scholar. In addition, the search was extended by screening the reference list of all articles.ResultsInnovative surgical approaches allowed direct access to symptomatic areas of the cervical spine. Over the years, we observed a trend from posterior to anterior surgical techniques. Management of the degenerative spine has evolved from decompressive surgery alone to the direct removal of the cause of neural impingement. Internal fixation of actual or potential spinal instability and the associated instrumentation have continuously evolved to allow more reliable fusion. More recently, surgeons have developed the basis for nonfusion surgical techniques and implants.ConclusionsThe most important advances appear to be (1) recognition of the need to directly address the causes of symptoms, (2) proper decompression of neural structures, and (3) more reliable fusion of unstable symptomatic segments.

Surgical management of cervical spine osteoblastomas.

The treatment of cervical spine osteoblastomas requires complex therapeutic and reconstructive strategies depending on the tumors location, local aggressiveness, and proximity to the surrounding neurovascular structures. Despite careful removal, lesions recur in as much as 10% of patients. Preoperative embolization is useful to minimize intraoperative bleeding and decrease the relapse of vascular tumors, but its role in osteoblastoma surgery is yet to be defined. We asked whether preoperative embolization with marginal resection would lead to osteoblastoma recurrence, and whether marginal excision with reconstruction would improve neurologic symptoms. We retrospectively analyzed a consecutive series of patients with cervical spine osteoblastoma, treated by one surgeon with a combined approach of preoperative embolization, marginal excision, and spinal reconstruction. One of nine patients presented with a monoradiculopathy, whereas only two patients presented with symptomatic spinal cord compression. At followup, all patients showed neurologic improvement, no tumor relapse, and adequate bony healing. Followup imaging studies showed cervical alignment was maintained. Although we report only a small uncontrolled cohort, the data suggest preoperative embolization and a tumor-free margin are consistent with a prolonged disease-free interval or complete tumor eradication.Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.