Application of Stem Cells in Orthopedics

Stem cell research plays an important role in orthopedic regenerative medicine today. Current literature provides us with promising results from animal research in the fields of bone, tendon, and cartilage repair. While early clinical results are already published for bone and cartilage repair, the data about tendon repair is limited to animal studies. The success of these techniques remains inconsistent in all three mentioned areas. This may be due to different application techniques varying from simple mesenchymal stem cell injection up to complex tissue engineering. However, the ideal carrier for the stem cells still remains controversial. This paper aims to provide a better understanding of current basic research and clinical data concerning stem cell research in bone, tendon, and cartilage repair. Furthermore, a focus is set on different stem cell application techniques in tendon reconstruction, cartilage repair, and filling of bone defects

Septic arthritis as a severe complication of elective arthroscopy:clinical management strategies

Infection of a peripheral joint following arthroscopic surgery presents with an incidence of approximately 0.42% an extremely rare entity. However, septic arthritis is a serious situation possibly leading to an irreparable joint damage. Especially at delayed diagnosis patients' safety can be endangered severely. Only few precise statements regarding diagnosis and therapy have been published so far. Besides an accurate analysis of the patient's anamnesis and the assessment of the C-reactive protein especially arthrocentesis is required for diagnostic workup. For early stage infections arthroscopic therapy is proven to be of value. In addition a calculated and consecutive germ-adjusted antibiotic therapy is essential. In case of persisting signs of infection the indication for re-arthroscopy or conversion to open revision has to be stated in time. The number of necessary revisions is dependent on the initial stage of infection. For pain therapy postoperative immobilization of the affected joint is occasionally essential, if otherwise possibly early mobilization of the joint should be performed

Extent of posterolateral tibial plateau impaction fracture correlates with anterolateral complex injury and has an impact on functional outcome after ACL reconstruction

PURPOSE The impact of posterolateral tibial plateau impaction fractures (TPIF) on posttraumatic knee stability in the setting of primary anterior cruciate ligament (ACL) tear is unknown. The main objective was to determine whether increased bone loss of the posterolateral tibial plateau is associated with residual rotational instability and impaired functional outcome after ACL reconstruction. METHODS A cohort was identified in a prospective enrolled study of patients suffering acute ACL injury who underwent preoperative standard radiographic diagnostics and clinical evaluation. Patients were included when scheduled for isolated single-bundle hamstring autograft ACL reconstruction. Exclusion criteria were concurrent anterolateral complex (ALC) reconstruction (anterolateral tenodesis), previous surgery or symptoms in the affected knee, partial ACL tear, multi-ligament injury with an indication for additional surgical intervention, and extensive cartilage wear. On MRI, bony (TPIF, tibial plateau, and femoral condyle morphology) and ligament status (ALC, concomitant collateral ligament, and meniscus injuries) were assessed by a musculoskeletal radiologist. Clinical evaluation consisted of KT-1000, pivot-shift, and Lachman testing, as well as Tegner activity and IKDC scores. RESULTS Fifty-eight patients were included with a minimum follow-up of 12 months. TPIF was identified in 85% of ACL injuries (n = 49). The ALC was found to be injured in 31 of 58 (53.4%) cases. Pearson analysis showed a positive correlation between TPIF and the degree of concomitant ALC injury (p < 0.001). Multiple regression analysis revealed an increased association of high-grade TPIF with increased lateral tibial convexity (p = 0.010). The high-grade TPIF group showed worse postoperative Tegner scores 12 months postoperatively (p = 0.035). CONCLUSION Higher degrees of TPIFs are suggestive of a combined ACL/ALC injury. Moreover, patients with increased posterolateral tibial plateau bone loss showed lower Tegner activity scores 12 months after ACL reconstruction. LEVEL OF EVIDENCE III

Tibial tunnel enlargement is affected by the tunnel diameter-screw ratio in tibial hybrid fixation for hamstring ACL reconstruction

INTRODUCTION There is no evidence on screw diameter with regards to tunnel size in anterior cruciate ligament reconstruction (ACLR) using hybrid fixation devices. The hypothesis was that an undersized tunnel coverage by the tibial screw leads to subsequent tunnel enlargement in ACLR in hybrid fixation technique. METHODS In a retrospective case series, radiographs and clinical scores of 103 patients who underwent primary hamstring tendon ACLR with a hybrid fixation technique at the tibial site (interference screw and suspensory fixation) were obtained. Tunnel diameters in the frontal and sagittal planes were measured on radiographs 6 weeks and 12 months postoperatively. Tunnel enlargement of more than 10% between the two periods was defined as tunnel widening. Tunnel coverage ratio was calculated as the tunnel diameter covered by the screw in percentage. RESULTS Overall, tunnel widening 12 months postoperatively was 23.1 ± 17.1% and 24.2 ± 18.2% in the frontal and sagittal plane, respectively. Linear regression analysis revealed the tunnel coverage ratio to be a negative predicting risk factor for tunnel widening (p = 0.001). The ROC curve analysis provided an ideal cut-off for tunnel enlargement of > 10% at a tunnel coverage ratio of 70% (sensitivity 60%, specificity 81%, AUC 75%, p  10% in the frontal plane if the tunnel coverage ratio was < 70% (sagittal plane: OR 14.7, p = 0.001). Clinical scores did not correlate to tunnel widening. CONCLUSION Tibial tunnel widening was affected by the tunnel diameter coverage ratio. To minimize the likelihood of disadvantageous tunnel expansion-which is of importance in case of revision surgery-an interference screw should not undercut the tunnel diameter by more than 1 mm

Calcium Alginate Gels as Stem Cell Matrix - Making Paracrine Stem Cell Activity Available for Enhanced Healing after Surgery

Regeneration after surgery can be improved by the administration of anabolic growth factors. However, to locally maintain these factors at the site of regeneration is problematic. The aim of this study was to develop a matrix system containing human mesenchymal stem cells (MSCs) which can be applied to the surgical site and allows the secretion of endogenous healing factors from the cells. Calcium alginate gels were prepared by a combination of internal and external gelation. The gelling behaviour, mechanical stability, surface adhesive properties and injectability of the gels were investigated. The permeability of the gels for growth factors was analysed using bovine serum albumin and lysozyme as model proteins. Human MSCs were isolated, cultivated and seeded into the alginate gels. Cell viability was determined by AlamarBlue assay and fluorescence microscopy. The release of human VEGF and bFGF from the cells was determined using an enzyme-linked immunoassay. Gels with sufficient mechanical properties were prepared which remained injectable through a syringe and solidified in a sufficient time frame after application. Surface adhesion was improved by the addition of polyethylene glycol 300, 000 and hyaluronic acid. Humans MSCs remained viable for the duration of 6 weeks within the gels. Human VEGF and bFGF was found in quantifiable concentrations in cell culture supernatants of gels loaded with MSCs and incubated for a period of 6 weeks. This work shows that calcium alginate gels can function as immobilization matrices for human MSCs

Calcium Alginate Gels as Stem Cell Matrix - Making Paracrine Stem Cell Activity Available for Enhanced Healing after Surgery

Regeneration after surgery can be improved by the administration of anabolic growth factors. However, to locally maintain these factors at the site of regeneration is problematic. The aim of this study was to develop a matrix system containing human mesenchymal stem cells (MSCs) which can be applied to the surgical site and allows the secretion of endogenous healing factors from the cells. Calcium alginate gels were prepared by a combination of internal and external gelation. The gelling behaviour, mechanical stability, surface adhesive properties and injectability of the gels were investigated. The permeability of the gels for growth factors was analysed using bovine serum albumin and lysozyme as model proteins. Human MSCs were isolated, cultivated and seeded into the alginate gels. Cell viability was determined by AlamarBlue assay and fluorescence microscopy. The release of human VEGF and bFGF from the cells was determined using an enzyme-linked immunoassay. Gels with sufficient mechanical properties were prepared which remained injectable through a syringe and solidified in a sufficient time frame after application. Surface adhesion was improved by the addition of polyethylene glycol 300, 000 and hyaluronic acid. Humans MSCs remained viable for the duration of 6 weeks within the gels. Human VEGF and bFGF was found in quantifiable concentrations in cell culture supernatants of gels loaded with MSCs and incubated for a period of 6 weeks. This work shows that calcium alginate gels can function as immobilization matrices for human MSCs

All-suture anchors for distal biceps tendon repair: a preliminary outcome study

Introduction: The aim of this study was to retrospectively evaluate the clinical outcome of double intramedullary all-suture anchors’ fixation for distal biceps tendon ruptures. Materials and methods: A retrospective case series of patients who underwent primary distal biceps tendon repair with all-suture anchors was conducted. Functional outcome was assessed at a minimum follow-up of at 12 months based on the assessments of the Mayo Elbow Performance Score (MEPS), Andrews–Carson Score (ACS), Quick Disabilities of the Arm, Shoulder, and Hand questionnaire (QuickDASH), and the Visual Analog Scale (VAS) for pain. Maximum isometric strength test for flexion and supination as well as postoperative range of motion (ROM) were determined for both arms. Results: 23 patients treated with all-suture anchors were assessed at follow-up survey (mean age 56.5 ± 11.4 years, 96% male). The follow-up time was 20 months (range Q$_{0.25}$–Q$_{0.75}$, 15–23 months). The following outcome results were obtained: MEPS 100 (range Q$_{0.25}$–Q$_{0.75}$, 100–100); ACS 200 (range Q$_{0.25}$–Q$_{0.75}$, 195–200); QuickDASH 31 (range Q$_{0.25}$–Q$_{0.75}$, 30–31); VAS 0 (range Q$_{0.25}$–Q$_{0.75}$, 0–0). The mean strength compared to the uninjured side was 95.6% (range Q$_{0.25}$–Q$_{0.75}$, 80.9–104%) for flexion and 91.8 ± 11.6% for supination. There was no significant difference in ROM or strength compared to the uninjured side and no complications were observed in any patient. Conclusion: Distal biceps tendon refixation using all-suture anchors provides good-to-excellent results in terms of patient-reported and functional outcome. This repair technique appears to be a viable surgical option, although further long-term results are needed

Age and gender as determinants of the bone quality of the greater tuberosity: A HR-pQCT cadaver study

Background: Age-dependent trabecular changes of the humeral head might weaken the fixation of suture anchors used for rotator cuff (RC) repair. This might lead to suture anchor loosening and thus compromise the integrity of the repair. The aim of this study was to analyze whether the trabecular microstructure within the RC footprint is influenced by age, gender or handedness. Methods: Axial HR-pQCT scans (Scanco Medical) of 64 freshly frozen cadaveric human humeral head specimens (age 72.3 +/- 17.4 years) were analyzed to determine the bone volume-to-total volume ratio (BV/TV), trabecular thickness (Trab Th), trabecular number (Trab N) and connectivity density (Conn Dens). Within the RC footprint, 2 volumes of interest (VOI), posteromedial (PM) and anterolateral (AL) and one control VOI in the subarticular bone (SC) were set. Results: The highest BV/TV was found in SC: 0.22 +/- 0.06% vs. PM: 0.04 +/- 0.05% vs. AL: 0.02 +/- 0.04%; p &lt; 0.05. Trab Th accounted for 0.26 +/- 0.05 mu m in SC, 0.23 +/- 0.09 mu m in AL and 0.21 +/- 0.05 mu m in PM. In parallel, Trab N and Conn Dens were found to be the highest in SC. Gender analysis yielded higher values for BV/TV, Trab Th, Trab N and Conn Dens for PM in males compared to females (p &lt; 0.05). There were no significant findings when comparing both sides. We furthermore found a strong inverse correlation between age and BV/TV, which was more pronounced in the female specimens (r = -0.72, p &lt; 0.00001). Conclusions: The presented microarchitectural data allow for future subtle biomechanical testing comprising knowledge on age-and sex-related changes of the tuberosities of the humeral head. Furthermore, the insights on the trabecular structure of the humeral head of the elderly may lead to the development of new fixation materials in bone with inferior bone quality

Biomechanical comparison of menisci from different species and artificial constructs

Background: Loss of meniscal tissue is correlated with early osteoarthritis but few data exist regarding detailed biomechanical properties (e. g. viscoelastic behavior) of menisci in different species commonly used as animal models. The purpose of the current study was to biomechanically characterize bovine, ovine, and porcine menisci (each n = 6, midpart of the medial meniscus) and compare their properties to that of normal and degenerated human menisci (n = 6) and two commercially available artificial scaffolds (each n = 3). Methods: Samples were tested in a cyclic, minimally constraint compression-relaxation test with a universal testing machine allowing the characterization of the viscoelastic properties including stiffness, residual force and relative sample compression. T-tests were used to compare the biomechanical parameters of all samples. Significance level was set at p &lt; 0.05. Results: Throughout cyclic testing stiffness, residual force and relative sample compression increased significantly (p &lt; 0.05) in all tested meniscus samples. From the tested animal meniscus samples the ovine menisci showed the highest biomechanical similarity to human menisci in terms of stiffness (human: 8.54 N/mm +/- 1.87, cycle 1; ovine: 11.24 N/mm +/- 2.36, cycle 1, p = 0.0528), residual force (human: 2.99 N +/- 0.63, cycle 1 vs. ovine 3.24 N +/- 0.13, cycle 1, p = 0.364) and relative sample compression (human 19.92\% +/- 0.63, cycle 1 vs. 18.72\% +/- 1.84 in ovine samples at cycle 1, p = 0.162). The artificial constructs - as hypothesized- revealed statistically significant inferior biomechanical properties. Conclusions: For future research the use of ovine meniscus would be desirable showing the highest biomechanical similarities to human meniscus tissue. The significantly different biomechanical properties of the artificial scaffolds highlight the necessity of cellular ingrowth and formation of extracellular matrix to gain viscoelastic properties. As a consequence, a period of unloading (at least partial weight bearing) is necessary, until the remodeling process in the scaffold is sufficient to withstand forces during weight bearing