Results of Surgical Treatment of Occult Spinal Dysraphisms-A Single Centre Experience.

Occult spinal dysraphisms (OSDs) are caused by various defects in the embryogenesis of the spinal cord and represent an obstacle to the ascent of the conus, which allows the conus to pass from the lower levels of the spinal canal to the final position between L1 and L2 during normal foetal life. When an OSD tethers the spinal cord at the lower levels, it can lead to neurological symptoms, better known as tethered cord syndrome. Surgical treatment of OSD is primarily aimed at untethering the spinal cord. In asymptomatic patients, this can protect against the long-term development of neurological deficits. In symptomatic patients, this can halt or limit the progression of existing symptoms. The aim of this study is to examine all paediatric and adult patients diagnosed with OSD and treated in the Department of Neurosurgery at the University Medical Centre Ljubljana during the 5-year period of 2016-2021. All patients diagnosed with OSD during this period were included in the study. Patient characteristics, treatment modalities and outcomes were studied with the aim of describing the differences between the paediatric and adult population and defining the rationality of treating these pathological conditions. We included in the study 52 patients with 64 occult dysraphic lesions. Adults (>18 years old) represented 15/52 (28.8%) of all patients, while 37/52 (71.8%) were children. The most common OSDs were conus lipomas, followed by dermal sinus tracts, filum terminale lipomas and split cord malformations. Surgical treatment was performed in 35/52 (67.3%) cases, while conservative management was chosen in 17/52 (32.6%) cases. The preoperative presence of symptoms was statistically higher in adults than in children (p = 0.0098). Surgery on complex spinal cord lipomas was statistically related to a higher rate of postoperative neurological complications (p = 0.0002). The treatment of OSD is complex and must be based on knowledge of the developmental anomalies of the spine and spinal cord. Successful surgical treatment relies on microsurgical techniques and the use of neuromonitoring. Successful treatment can prevent or limit the occurrence of neurological problems.

Isolated Sagittal Craniosynostosis: A Comprehensive Review.

Sagittal craniosynostosis, a rare but fascinating craniofacial anomaly, presents a unique challenge for both diagnosis and treatment. This condition involves premature fusion of the sagittal suture, which alters the normal growth pattern of the skull and can affect neurological development. Sagittal craniosynostosis is characterised by a pronounced head shape, often referred to as scaphocephaly. Asymmetry of the face and head, protrusion of the fontanel, and increased intracranial pressure are common clinical manifestations. Early recognition of these features is crucial for early intervention, and understanding the aetiology is, therefore, essential. Although the exact cause remains unclear, genetic factors are thought to play an important role. Mutations in genes such as FGFR2 and FGFR3, which disrupt the normal development of the skull, are suspected. Environmental factors and various insults during pregnancy can also contribute to the occurrence of the disease. An accurate diagnosis is crucial for treatment. Imaging studies such as ultrasound, computed tomography, magnetic resonance imaging, and three-dimensional reconstructions play a crucial role in visualising the prematurely fused sagittal suture. Clinicians also rely on a physical examination and medical history to confirm the diagnosis. Early detection allows for quick intervention and better treatment outcomes. The treatment of sagittal craniosynostosis requires a multidisciplinary approach that includes neurosurgery, craniofacial surgery, and paediatric care. Traditional treatment consists of an open reconstruction of the cranial vault, where the fused suture is surgically released to allow normal growth of the skull. However, advances in minimally invasive techniques, such as endoscopic strip craniectomy, are becoming increasingly popular due to their lower morbidity and shorter recovery times. This review aims to provide a comprehensive overview of sagittal craniosynostosis, highlighting the aetiology, clinical presentation, diagnostic methods, and current treatment options.

Stem cell therapy for degenerative disc disease: Bridging the gap between preclinical promise and clinical potential.

Stem cell therapy has gained attention in the field of regenerative medicine due to its potential to restore damaged tissue. This article focuses on the application of stem cell therapy for treating spinal pathologies, particularly intervertebral disc degeneration. Disc degeneration is a major cause of low back pain and is characterized by changes in the matrix and inflammation. Animal studies have demonstrated that the implantation of mesenchymal stem cells (MSCs) yields promising results, including increased disc height, improved hydration, and reduced inflammation. However, the number of clinical trials remains limited, necessitating further research to optimize MSCs therapy. Although preclinical studies offer valuable insights, caution is needed when extrapolating these findings to clinical practice. Stem cell therapy still faces multiple challenges, such as the durability and survival of MSCs upon implantation, uncertain pathways to discogenic differentiation, and the adverse impact of a harsh microenvironment on cell survival. The avascular nature of the intervertebral disc and dynamic loading conditions also affect the adaptation of transplanted cells. Despite these obstacles, stem cell therapy holds promise as a potential treatment for disc degeneration, and ongoing research aims to fill the current gap in conclusive data.

Biparietal remodelling and total vault remodelling in scaphocephaly-a comparative study using 3d stereophotogrammetry.

PURPOSE: The aim of the study was to compare the results of two surgical techniques for the treatment of isolated sagittal synostosis (ISS) by means of 3D stereophotogrammetry. One technique, the Renier's "H" technique (RHT) comprised a biparietal expansion, the other, the total vault remodeling (TVR) included also a frontal remodeling. METHODS: The two groups of operated children were compared with a third control group of normocephalic children. The 3D scanning was performed in all children between 12 and 245 months of age. On each 3D image six measurements and indices have been made, with the aim of evaluating not only length and width of the head, but also the height. The cranial index (CI) was measured in a plane parallel to the nasion-tragus plane, at the intersection with the opisthocranion. RESULTS: Each of the three groups (RHT, TVR, control group) included 28 children. The measurements that were influenced by the correction of the frontal bossing, namely the CI and the sagittal length, were closer to normocephaly after TVR than after RHT. Lesser or no statistical difference was documented in the measurements evaluating the biparietal aspect and the height of the vertex, indicating that the biparietal expansion is effective in both procedures. CONCLUSION: Based on our results TVR results in a better esthetical outcome, particularly in relation to the direct surgical remodeling of the frontal bossing.

COVID-19 and Surgical Practice in Slovenia: Managing the Crisis in Neurosurgery during the COVID-19 Pandemic.

Worldwide, the novel coronavirus disease 2019 (COVID-19) has become a significant threat to global health. Worldwide, COVID-19 has affected the health service also in Slovenia. During this time, neurosurgery is facing difficulties in its service, both in emergency and elective surgeries. In the article, we describe the anti-COVID-19 measures taken at our neurosurgical department in a medical centre in Ljubljana, Slovenia, and analysed and compared the number of emergency and elective neurosurgical procedures during the time of the pandemic.

The Brainstem Cavernoma Case Series: A Formula for Surgery and Surgical Technique.

Background and Objectives: Cavernous malformations (CM) are vascular malformations with low blood flow. The removal of brainstem CMs (BS) is associated with high surgical morbidity, and there is no general consensus on when to treat deep-seated BS CMs. The aim of this study is to compare the surgical outcomes of a series of deep-seated BS CMs with the surgical outcomes of a series of superficially located BS CMs operated on at the Department of Neurosurgery, College of Tuebingen, Germany. Materials and Methods: A retrospective evaluation was performed using patient charts, surgical video recordings, and outpatient examinations. Factors were identified in which surgical intervention was performed in cases of BS CMs. Preoperative radiological examinations included MRI and diffusion tensor imaging (DTI). For deep-seated BS CMs, a voxel-based 3D neuronavigation system and electrophysiological mapping of the brainstem surface were used. Results: A total of 34 consecutive patients with primary superficial (n = 20/58.8%) and deep-seated (n = 14/41.2%) brainstem cavernomas (BS CM) were enrolled in this comparative study. Complete removal was achieved in 31 patients (91.2%). Deep-seated BS CMs: The mean diameter was 14.7 mm (range: 8.3 to 27.7 mm). All but one of these lesions were completely removed. The median follow-up time was 5.8 years. Two patients (5.9%) developed new neurologic deficits after surgery. Superficial BS CMs: The median diameter was 14.9 mm (range: 7.2 to 27.3 mm). All but two of the superficial BS CMs could be completely removed. New permanent neurologic deficits were observed in two patients (5.9%) after surgery. The median follow-up time in this group was 3.6 years. Conclusions: The treatment of BS CMs remains complex. However, the results of this study demonstrate that with less invasive posterior fossa approaches, brainstem mapping, and neuronavigation combined with the use of a blunt "spinal cord" dissection technique, deep-seated BS CMs can be completely removed in selected cases, with good functional outcomes comparable to those of superficial BS CM.

Clinical infections in neurosurgical oncology: An overview.

Central nervous system (CNS) infections are urgent conditions with high morbidity and mortality. Bacteria, viruses, parasites or fungi can cause them. Intracranial infections after craniotomies are an important complication of treatment, especially in oncological patients that are already immunologically compromised due to the disease and treatment. The consequence of CNS infections in oncological patients includes longer treatment with antibiotics, additional surgical procedures, higher treatment costs and poorer treatment outcomes. Additionally, the management of primary pathology may be prolonged or postponed as a result of the active infection. By introducing new and improved protocols, tightening controls on their implementation, constantly educating the entire team involved in patient treatment and educating both patients and relatives, the incidence of infections can be reduced effectively.

Astrocytes in the central nervous system and their functions in health and disease: A review.

Astrocytes are key cells in the central nervous system. They are involved in many important functions under physiological and pathological conditions. As part of neuroglia, they have been recognised as cellular elements in their own right. The name astrocyte was first proposed by Mihaly von Lenhossek in 1895 because of the finely branched processes and star-like appearance of these particular cells. As early as the late 19th and early 20th centuries, Ramon y Cajal and Camillo Golgi had noted that although astrocytes have stellate features, their morphology is extremely diverse. Modern research has confirmed the morphological diversity of astrocytes both in vitro and in vivo and their complex, specific, and important roles in the central nervous system. In this review, the functions of astrocytes and their roles are described.

Awake craniotomy for operative treatment of brain gliomas - experience from University Medical Centre Ljubljana.

BACKGROUND: Awake craniotomy is a neurosurgical technique that allows neurophysiological testing with patient cooperation during the resection of brain tumour in regional anaesthesia. This allows identification of vital functional (i.e. eloquent) brain areas during surgery and avoidance of their injury. The aim of the study was to present clinical experience with awake craniotomy for the treatment of gliomas at the University Medical Centre Ljubljana from 2015 to 2019. PATIENTS AND METHODS: Awake craniotomy was considered in patients with a gliomas near or within the language brain areas, in all cases of insular lesions and selected patients with lesions near or within primary motor brain cortex. Each patient was assessed before and after surgery. RESULTS: During the 5-year period, 24 awake craniotomies were performed (18 male and 6 female patients; average age 41). The patient's cooperation, discomfort and perceived pain assessed during the awake craniotomy were in majority of the cases excellent, slight, and moderate, respectively. After surgery, mild neurological worsening was observed in 13% (3/24) of patients. Gross total resection, in cases of malignant gliomas, was feasible in 60% (6/10) and in cases of low-grade gliomas in 29% (4/14). The surgery did not have important negative impact on functional status or quality of life as assessed by Karnofsky score and Short-Form 36 health survey, respectively (p > 0.05). CONCLUSIONS: The results suggest that awake craniotomy for treatment of gliomas is feasible and safe neurosurgical technique. The proper selection of patients, preoperative preparation with planning, and cooperation of medical team members are necessary for best treatment outcome.

Endplate role in the degenerative disc disease: A brief review.

The degenerative disease of the intervertebral disc is nowadays an important health problem, which has still not been understood and solved adequately. The vertebral endplate is regarded as one of the vital elements in the structure of the intervertebral disc. Its constituent cells, the chondrocytes in the endplate, may also be involved in the process of the intervertebral disc degeneration and their role is central both under physiological and pathological conditions. They main functions include a role in homeostasis of the extracellular environment of the intervertebral disc, metabolic support and nutrition of the discal nucleus and annulus beneath and the preservation of the extracellular matrix. Therefore, it is understandable that the cells in the endplate have been in the centre of research from several viewpoints, such as development, degeneration and growth, reparation and remodelling, as well as treatment strategies. In this article, we briefly review the importance of vertebral endplate, which are often overlooked, in the intervertebral disc degeneration.

Problematics of neurosurgical service during the COVID-19 pandemic in Slovenia.

The novel coronavirus disease 2019 (COVID-19) is an ongoing disease caused by severe acute respiratory syndrome coronavirus-2 that still poses an important and urgent threat to global health. In Slovenia, the epidemic was declared on March 12th, 2020, and since then COVID-19 has had a great impact on our health system. The field of neurosurgery in particular has been experiencing difficulties in both elective and emergency service. In this article, we described epidemiologic protocols and the effect that the COVID-19 pandemic had on the surgical practice and workflow of the Department of Neurosurgery at the University Medical Centre Ljubljana. We analyzed and compared the number of elective and emergency neurosurgical procedures in a 2-year period before and during the pandemic. We recorded a drop in cases mostly on account of elective procedures whilst emergency service remained relatively unaffected.

A Review Pertaining to SARS-CoV-2 and Autoimmune Diseases: What Is the Connection?

Coronavirus disease 2019 (COVID-19) is an infectious viral disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It is known that infection with SARS-CoV-2 can lead to various autoimmune and autoinflammatory diseases. There are few reports in the literature on the association between SARS-CoV-2 and autoimmune diseases, and the number of reports has been increasing since 2020. Autoimmune diseases and SARS-CoV-2 infections are intertwined in several ways. Both conditions lead to immune-mediated tissue damage, the immune response is accompanied by the increased secretion of inflammatory cytokines and both conditions can be treated using immunomodulatory drugs. Patients with certain autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, cardiac sarcoidosis, idiopathic pulmonary fibrosis, autoimmune hepatitis, multiple sclerosis and others, are more susceptible to SARS-CoV-2 infection, either because of the active autoimmune disease or because of the medications used to treat it. Conversely, SARS-CoV-2 infection can also cause certain autoimmune diseases. In this paper, we describe the development of autoimmune diseases after COVID-19 and the recovery from COVID-19 in people with autoimmune diseases.

Clinical Applications of Poly-Methyl-Methacrylate in Neurosurgery: The In Vivo Cranial Bone Reconstruction.

BACKGROUND: Biomaterials and biotechnology are becoming increasingly important fields in modern medicine. For cranial bone defects of various aetiologies, artificial materials, such as poly-methyl-methacrylate, are often used. We report our clinical experience with poly-methyl-methacrylate for a novel in vivo bone defect closure and artificial bone flap development in various neurosurgical operations. METHODS: The experimental study included 12 patients at a single centre in 2018. They presented with cranial bone defects after various neurosurgical procedures, including tumour, traumatic brain injury and vascular pathologies. The patients underwent an in vivo bone reconstruction from poly-methyl-methacrylate, which was performed immediately after the tumour removal in the tumour group, whereas the trauma and vascular patients required a second surgery for cranial bone reconstruction due to the bone decompression. The artificial bone flap was modelled in vivo just before the skin closure. Clinical and surgical data were reviewed. RESULTS: All patients had significant bony destruction or unusable bone flap. The tumour group included five patients with meningiomas destruction and the trauma group comprised four patients, all with severe traumatic brain injury. In the vascular group, there were three patients. The average modelling time for the artificial flap modelling was approximately 10 min. The convenient location of the bone defect enabled a relatively straightforward and fast reconstruction procedure. No deformations of flaps or other complications were encountered, except in one patient, who suffered a postoperative infection. CONCLUSIONS: Poly-methyl-methacrylate can be used as a suitable material to deliver good cranioplasty cosmesis. It offers an optimal dural covering and brain protection and allows fast intraoperative reconstruction with excellent cosmetic effect during the one-stage procedure. The observations of our study support the use of poly-methyl-methacrylate for the ad hoc reconstruction of cranial bone defects.

Management of neurosurgical patients during coronavirus disease 2019 pandemics: The Ljubljana, Slovenia experience.

The novel coronavirus disease 2019 (COVID-19) is an emerging disease, caused by severe acute respiratory syndrome coronavirus-2. It bears unique biological characteristics, clinical symptoms and imaging manifestations, therefore presenting an important and urgent threat to global health. As a result, a new public health crisis arose, threatening the world with the spread of the 2019 novel coronavirus. Despite the maximal worldwide public health responses aimed at containing the disease and delaying its spread, many countries have been confronted with a critical care crisis, and even more, countries will almost certainly follow. In Slovenia, the COVID-19 has struck the health system immensely and among all the specialities, neurosurgery has also been experiencing difficulties in the service, not only in regular, elective surgeries but especially during emergencies. The management of these neurosurgical patients has become more difficult than ever. We describe our protocol in the management of neurosurgical patients in the University Medical Centre Ljubljana, Slovenia and how neurosurgical pathology was tackled during the pandemics.

Craniofacial reconstructions in children with craniosynostosis.

BACKGROUND: Craniosynostosis is a rare congenital disease of the skull. They arise when one or more cranial sutures ossify prematurely. This causes an obstruction to normal brain growth and leads to specific deformations of the skull, which may result in intracranial hypertension and cognitive delay. MATERIALS AND METHODS: We have retrospectively analysed all children treated at the Unit of paediatric neurosurgery of the University Medical Centre Ljubljana between June 2015 and September 2020. The following items have been recorded: affected suture, underlying syndromic condition, hydrocephalus, Chiari malformation, raised intracranial pressure, age at surgery, surgical technique, need for multiple operations and surgical complications. RESULTS: During the study period, 71 children have been treated for craniosynostosis. The median postoperative follow-up was 31 months. There were: 54.9% sagittal, 25.3% metopic, 14.0% unicoronal, 1.4% bicoronal and 1.4% unilateral lambdoid craniosynostosis. Multiple sutures were affected in 2.8% cases. 7.0% of the cases were syndromic. Overall, 74 surgical procedures have been performed: frontoorbital advancement represented 40.5% of them; biparietal remodelling 32.4%: total cranial vault remodelling 22.9%; posterior distraction 2.7%; posterior expansion 1.3%. Median age at surgery was 12.8 months. CONCLUSIONS: The treatment of craniosynostosis is surgical and requires a multidisciplinary approach, with expertise in plastic and reconstructive surgery, maxillofacial surgery and neurosurgery. The aim of surgical treatment is to release the constrictive and deformative effect that the synostosis has on skull growth. This requires a remodelling of the neurocranium and, if necessary, of the viscerocranium. Beyond aesthetic purposes, the primary aim of surgical treatment is to permit a normal development of the brain.

Selective dorsal rhizotomy: short-term results and early experiences with a newly established surgical treatment in Slovenia.

BACKGROUND: Spasticity is characterised by an atypical increase of muscle tone, affecting normal movements and interfering with the patient quality of life. The medicines may limit the effects of the disease and selective dorsal rhizotomy (SDR) can be used for selected cases or cases refractory to medicine. We present the surgical technique and the short-term results of this newly established surgical treatment in Slovenia. METHODS: A retrospective analysis was performed of all patients that underwent the SDR from 2017 to 2019. The median follow-up was of 10 months. The following data have been collected: aetiology of spasticity, age at SDR, number of sectioned lumbar rootlets L1-S2, intraoperative disappearance of the H-reflex and intraoperative preservation of the bulbocavernosus reflex. The motor functions of all children have been classified by the Gross Motor Function Classification System (GMFCS) and Gross Motor Function Measure (GMFM-88). Twelve children underwent SDR, the median age at surgery was 9.6 years (min 3.9-max 16 years). RESULTS: A mean of 57.8% of dorsal rootlets L2-S1 have been cut, while at level L1 50% of the dorsal roots have been routinely sectioned. The median amount of S2 rootlets cut was 14.3%. Postoperatively, we observed a sudden decrease in muscle tone. In all patients, there was an improvement of the muscle tone and of the gait pattern. The GMFM improved from 187.8 to 208.3 after a follow-up of 6 months. CONCLUSIONS: There was no complication in terms of wound healing, cerebrospinal fluid fistula of neurological dysfunctions. Despite the relatively short follow-up, our early results confirm the efficacy of the SDR.

The Endplate Role in Degenerative Disc Disease Research: The Isolation of Human Chondrocytes from Vertebral Endplate-An Optimised Protocol.

BACKGROUND: Degenerative disc disease is a progressive and chronic disorder with many open questions regarding its pathomorphological mechanisms. In related studies, in vitro organ culture systems are becoming increasingly essential as a replacement option for laboratory animals. Live disc cells are highly appealing to study the possible mechanisms of intervertebral disc (IVD) degeneration. To study the degenerative processes of the endplate chondrocytes in vitro, we established a relatively quick and easy protocol for isolating human chondrocytes from the vertebral endplates. METHODS: The fragments of human lumbar endplates following lumbar fusion were collected, cut, ground and partially digested with collagenase I in Advanced DMEM/F12 with 5% foetal bovine serum. The sediment was harvested, and cells were seeded in suspension, supplemented with special media containing high nutrient levels. Morphology was determined with phalloidin staining and the characterisation for collagen I, collagen II and aggrecan with immunostaining. RESULTS: The isolated cells retained viability in appropriate laboratory conditions and proliferated quickly. The confluent culture was obtained after 14 days. Six to 8 h after seeding, attachments were observed, and proliferation of the isolated cells followed after 12 h. The cartilaginous endplate chondrocytes were stable with a viability of up to 95%. Pheno- and geno-typic analysis showed chondrocyte-specific expression, which decreased with passages. CONCLUSIONS: The reported cell isolation process is simple, economical and quick, allowing establishment of a viable long-term cell culture. The availability of a vertebral endplate cell model will permit the study of cell properties, biochemical aspects, the potential of therapeutic candidates for the treatment of disc degeneration, and toxicology studies in a well-controlled environment.

Astrocytes and human artificial blood-brain barrier models.

The blood-brain barrier (BBB) functions as a highly selective border of endothelial cells, protecting the central nervous system from potentially harmful substances by selectively controlling the entry of cells and molecules, including components of the immune system. To study the BBB properties, find suitable therapies, and identify new drug targets, there is a need to develop representative in vitro BBB models. In this article, we describe the astrocyte roles in the BBB functioning and human in vitro BBB models.

Impact of a 12-month multifaceted neurological physiotherapy intervention on gross motor function in women with Rett syndrome.

BACKGROUND: Rett syndrome is a rare genetic neurological syndrome that affects mostly females. The syndrome leads to severe impairments impacting all areas of the affected persons' life, including speech, mobility, eating, and breathing impairments. The most distinct symptoms include stereotyped hand movements, ataxia, and atrophy of the lower limbs, and signs of autism. METHODS: According to the principle of convenience sampling, the quantitative research included five females diagnosed with Rett syndrome subject to their personalized goal oriented neurological physiotherapy. Changes in gross motor function were assessed by the Gross Motor Function Measure 88 and Rett syndrome Gross Motor Scale. RESULTS: It was found that the 12-month multifaceted neurological physiotherapy intervention had statistically significant improvements in both Gross Motor Function Measure 88 (p = 0.005) and Rett syndrome Gross Motor Scale (p = 0.012). Despite positive improvements, the absence of control group made it difficult for a comparative evaluation to determine what interventions had the best possible outcomes. CONCLUSIONS: The quantitative research demonstrates neuro-developmental treatment sessions, hippotherapy, hydrotherapy, physical therapy, a walking program, endurance exercises, active-assisted exercises, and coordination exercises, had a significant impact on improving gross motor function status. Current multifaceted intervention program leads to good improvement of gross motor skills above what can be expected from late motor deterioration.

Mesenchymal Stem Cells Isolated from Paediatric Paravertebral Adipose Tissue Show Strong Osteogenic Potential.

Mesenchymal stem cells (MSCs) represent the basis of novel clinical concepts in cellular therapy and tissue regeneration. Therefore, the isolation of MSCs from various tissues has become an important endeavour for stem cell biobanking and the development of regenerative therapies. Paravertebral adipose tissue is readily exposed during spinal procedures in children and could be a viable source of stem cells for therapeutic applications. Here, we describe the first case of MSCs isolated from paravertebral adipose tissue (PV-ADMSCs), obtained during a routine spinal surgery on a child. Using quantitative real-time PCR and flow cytometry, we show that PV-ADMSCs have different levels of stem marker expression compared to the MSCs from other sources while having the highest proliferation rate. Furthermore, we evaluate the multipotency of PV-ADMSCs by the three-lineage (adipogenic, osteogenic and chondrogenic) differentiation and compare it to the multipotency of MSCs from other sources. It was found that the PV-ADMSCs have a strong osteogenic potential in particular. Taken together, our data indicate that PV-ADMSCs meet the criteria for successful cell therapy, defined by the International Society for Cellular Therapy (ISCT), and thus, could provide a source of MSCs that is relatively easy to isolate and expand in culture. Due to their strong osteogenic potential, these cells provide a promising basis, especially for orthopaedic applications.