Pavel Šponer

The role of mesenchymal stem cells in bone repair and regeneration

Despite the undisputed modern development of synthetic biomaterials that range from bioactive unresorbable to restorable materials, clinically applied osteoconduction bone substitutes still have limitations in the treatment of bone defects. These are the result of the physical and chemical properties of the utilized materials and the biological interactions associated with both local and general reactions of the organism. Mesenchymal stem cells constitute a promising treatment alternative in orthopedics. Preclinical studies regarding the use of mesenchymal stem cells have shown good therapeutic results. However, it is still necessary to advance further in this area and enable the treatment of patients with critically large bone defects. The aim of this review is to describe the role of mesenchymal stem cells in bone repair and regeneration, describe the techniques used in the clinical application of mesenchymal stem cells and outline future research endeavors in this area.

TOTAL HIP ARTHROPLASTY IN PATIENTS WITH PARKINSON'S DISEASE

The aim of this study is to evaluate the results of total hip arthroplasty in patients with Parkinsons disease during a period of five years, focusing on the assessment of the risks and benefits of surgery. During this period we performed total hip arthroplasty in 14 patients (15 hips) with Parkinsons disease. Patients were evaluated by subjective symptoms and objective findings, with a focus on the use of support while walking and walking distance, severity of Parkinsons disease before surgery and at the time of the last follow-up. During the postoperative period, the following parameters were assessed: length of ICU stay, mobilization, complications, the total duration of hospitalization and follow-up care after discharge. Of the 11 patients (12 hips) followed-up 1-5 years with an average of 3 years after operation 8 cases showed progression of neurological disability. 5 patients (6 hips) showed an increased dependence on the use of support when walking and reduced distance that the patient was able to walk. Subjectively, 10 hip joints were completely painless and 2 patients complained of only occasional mild pain in the operated hip. Complications that were encountered were urinary tract infection (5 patients), cognitive impairment (3 patients) and pressure ulcer (2 patients). We did not observe any infection or dislocation of the prosthesis. Three patients fell and fractured the femur and 3 patients in our cohort died during follow up. Implantation of total replacement is possible with judicious indication after careful evaluation of neurological finding in patients with minimal or mild functional impairment of the locomotor system. Prerequisite for a good result is precise surgical technique and optimal implant position with balanced tension of the muscles and other soft tissues around the hip.

In vivo behaviour of low-temperature calcium-deficient hydroxyapatite: comparison with deproteinised bovine bone

This study aims to evaluate in detail the biological osteoconductive properties of the low-temperature synthetic porous calcium-deficient hydroxyapatite and to compare it with the biological apatite. Bone reactions to granules of similar sizes of the low-temperature hydroxyapatite and commercially available non-sintered deproteinized bovine bone were compared. Two different temperatures were used to fabricate two batches of newly developed porous hydroxyapatite with different carbonate groups content and specific surface area. The histological analysis of specimens with histomorphometry was performed at different time after in vivo implantation. Based on histological analysis, the level of bone formation in the spaces between the implanted granules and through the interconnected pores of all implanted materials within a cortical region (bone area ingrowth 72–85 %) was several-fold higher than within a cancellous bone site (bone area ingrowth 16–28 %) at three and six months after implantation. Within the cancellous bone site, bone coverage of the implanted material at six months was significantly higher in hydroxyapatite material fabricated using low-temperature synthesis and subsequent processing at 150°C than in hydroxyapatite scaffold developed using low-temperature synthesis with subsequent processing at 700°C or deproteinized bovine bone. According to our study, the bioactive properties of the low-temperature calcium-deficient hydroxyapatite are comparable with the biological apatite. The favourable influence of a high specific surface area of a low-temperature calcium-deficient hydroxyapatite on in vivo bone formation was emphasized.

Behavior of bioactive glass-ceramic implanted into long bone defects: a scintigraphic study.

The purpose of the study was to assess the long-term behavior and incorporation of the bioactive oxyhydroxyapatite glass-ceramic used to fill defects of long bones after curettage of bone cysts in 17 patients. The method of evaluation was a three-phase bone scintigraphy combined with radiographic and clinical evaluation. At a mean follow-up of 7 years, the glass-ceramic material had been completely incorporated. Mean uptake ratio was 1.31±0.25 after implantation of glass-ceramic in the metaphyseal region and 2.07±0.62 after implantation of glass-ceramic in the diaphyseal region (P<0.05). Mean uptake ratio was 1.40±0.30 in patients without persistent pain and 2.07±0.69 in patients who complained of pain in the area of synthetic filling (P<0.05). The bioactive glass-ceramic can be implanted into the metaphyseal defects of long bones, but this material is not suitable for filling the diaphyseal defects.

Charcot Neuropathic Arthropathy of the Foot: A Literature Review and Single-Center Experience

Charcot neuropathic osteoarthropathy of the foot is a relatively common complication of diabetic neuropathy. Incorrect diagnosis and improper treatment often result in the extremity having to be amputated. This paper summarises the current view on the etiology, diagnostics, and treatment of diabetic Charcot neuropathic osteoarthropathy, with particular focus on preserving the extremity through surgical intervention from our own experiences.

Utilizing Autologous Multipotent Mesenchymal Stromal Cells and β-Tricalcium Phosphate Scaffold in Human Bone Defects: A Prospective, Controlled Feasibility Trial

The purpose of this prospective controlled study was to compare healing quality following the implantation of ultraporous β-tricalcium phosphate, containing either expanded autologous mesenchymal stromal cells (trial group, 9 patients) or β-tricalcium phosphate alone (control group, 9 patients), into femoral defects during revision total hip arthroplasty. Both groups were assessed using the Harris Hip Score, radiography, and DEXA scanning at 6 weeks and 3, 6, and 12 months postoperatively. A significant difference in the bone defect healing was observed between both groups of patients (P < 0.05). In the trial group, trabecular remodeling was found in all nine patients and in the control group, in 1 patient only. Whereas, over the 12-month follow-up period, no significant difference was observed between both groups of patients in terms of the resorption of β-tricalcium phosphate, the significant differences were documented in the presence of radiolucency and bone trabeculation through the defect (P < 0.05). Using autologous mesenchymal stromal cells combined with a β-tricalcium phosphate scaffold is a feasible, safe, and effective approach for management of bone defects with compromised microenvironment. The clinical trial was registered at the EU Clinical Trials Register before patient recruitment has begun (EudraCT number 2012-005599-33).

Pyogenic sacroiliitis: diagnosis, management and clinical outcome

ObjectiveThe purpose of the present study was to evaluate the role of diagnostic tools and management options for patients with pyogenic sacroiliitis, including potential complications.Materials and methodsThis retrospective study included 16 patients with pyogenic sacroiliitis who were admitted to a single orthopaedic centre between 2007 and 2012. The following data were collected: demographics, history, radiography, magnetic resonance images (MRI), biological data, type of pathogenic agent, abscess formation, type of management, and clinical outcome.ResultsOur study demonstrated that only one-fifth of the patients with lumbogluteal or hip pain had established diagnoses of suspected pyogenic sacroiliitis upon admission. MRIs confirmed this diagnosis in all cases. MRI examinations revealed joint fluid in the sacroiliac joint and significant oedema of the adjacent bone and soft tissues. In 12 of the 16 cases, erosions of the subchondral bone were encountered. Contrast-enhanced MRI revealed that 9 patients had abscesses. All patients received antibiotic therapy. Antibiotic treatment was only successful in 9 cases. The other 7 patients underwent computed tomography (CT)-guided abscess drainage. Drainage was sufficient for 4 patients, but 3 patients required open surgery. One patient required sacroiliac arthrodesis. The clinical outcomes included minimal disability (n = 10), moderate disability (n = 5), and full disability (n = 1) of the spine.ConclusionsContrast-enhanced MRI is mandatory for a reliable diagnosis. Abscess formation was observed in approximately half of the MRI-diagnosed sacroiliitis cases and required minimally invasive drainage under CT guidance or frequently open surgery.

The peripheral chimerism of bone marrow–derived stem cells after transplantation: regeneration of gastrointestinal tissues in lethally irradiated mice

Bone marrow–derived cells represent a heterogeneous cell population containing haematopoietic stem and progenitor cells. These cells have been identified as potential candidates for use in cell therapy for the regeneration of damaged tissues caused by trauma, degenerative diseases, ischaemia and inflammation or cancer treatment. In our study, we examined a model using whole‐body irradiation and the transplantation of bone marrow (BM) or haematopoietic stem cells (HSCs) to study the repair of haematopoiesis, extramedullary haematopoiesis and the migration of green fluorescent protein (GFP+) transplanted cells into non‐haematopoietic tissues. We investigated the repair of damage to the BM, peripheral blood, spleen and thymus and assessed the ability of this treatment to induce the entry of BM cells or GFP+lin−Sca‐1+ cells into non‐haematopoietic tissues. The transplantation of BM cells or GFP+lin−Sca‐1+ cells from GFP transgenic mice successfully repopulated haematopoiesis and the haematopoietic niche in haematopoietic tissues, specifically the BM, spleen and thymus. The transplanted GFP+ cells also entered the gastrointestinal tract (GIT) following whole‐body irradiation. Our results demonstrate that whole‐body irradiation does not significantly alter the integrity of tissues such as those in the small intestine and liver. Whole‐body irradiation also induced myeloablation and chimerism in tissues, and induced the entry of transplanted cells into the small intestine and liver. This result demonstrates that grafted BM cells or GFP+lin−Sca‐1+ cells are not transient in the GIT. Thus, these transplanted cells could be used for the long‐term treatment of various pathologies or as a one‐time treatment option if myeloablation‐induced chimerism alone is not sufficient to induce the entry of transplanted cells into non‐haematopoietic tissues.

Our approach to the spastic hip subluxation and dislocation in children with cerebral palsy.

The purpose of this study was to evaluate the effectiveness of our approach to the spastic hip subluxation and dislocation in children with cerebral palsy. We evaluated 56 hips in our consecutive patients who had been operated on at our department between January 2003 and December 2005. There were done soft-tissue release procedures in 42 hips, osseous reconstructive surgery in 11 hips and osseous palliative surgery in 3 hips. The duration of follow-ups was 1-3 years after surgery. We achieved good result in 15 hips after soft-tissue release, fifteen hips had a fair result, nine a poor result and three a failure. No redislocation was observed after osseous surgery in our patients. Two patients observed no pain after osseous palliative surgery, transient pain in the hip was in one case. In all hips the range of motion (abduction) was increased. The personal hygiene and possibilities of rehabilitation were improved. Childhood is the optimal time to intervene to maximize the function of the patient with cerebral palsy. The musculoskeletal treatment of the child prevents future problems with pain and deformity.

THE MANAGEMENT OF CHARCOT MIDFOOT DEFORMITIES IN DIABETIC PATIENTS

Charcot foot neuropathic osteoarthropathy is a disorder affecting the soft tissues, joints, and bones of the foot and ankle. The disease is triggered in a susceptible individual through a process of uncontrolled inflammation leading to osteolysis, progressive fractures and articular malpositioning due to joint subluxations and dislocations. The progression of the chronic deformity with a collapsed plantar arch leads to plantar ulcerations because of increased pressure on the plantar osseous prominences and decreased plantar sensation. Subsequent deep soft tissue infection and osteomyelitis may result in amputation. The Charcot foot in diabetes represents an important diagnostic and therapeutic challenge in clinical practice. Conservative treatment remains the standard of the care for most patients with neuropathic disorder. Offloading the foot and immobilization based on individual merit are essential and are the most important recommendations in the active acute stage of the Charcot foot. Surgical realignment with stabilization is recommended in severe progressive neuropathic deformities consisting of a collapsed plantar arch with a rocker-bottom foot deformity.