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Regenerative therapies in the musculoskeletal system are based on the suitable application of cells, biomaterials, and/or factors. For an effective approach, numerous aspects have to be taken into consideration, including age, disease, target tissue, and several environmental factors. Significant research efforts have been undertaken in the last decade to develop specific cell‐based therapies, and in particular adult multipotent mesenchymal stem cells hold great promise for such regenerative strategies. Clinical translation of such therapies, however, remains a work in progress. In the clinical arena, autologous cells have been harvested, processed, and readministered according to protocols distinct for the target application. As outlined in this review, such applications range from simple single‐step approaches, such as direct injection of unprocessed or concentrated blood or bone marrow aspirates, to fabrication of engineered constructs by seeding of natural or synthetic scaffolds with cells, which were released from autologous tissues and propagated under good manufacturing practice conditions (for example, autologous chondrocyte implantation). However, only relatively few of these cell‐based approaches have entered the clinic, and none of these treatments has become a “standard of care” treatment for an orthopaedic disease to date. The multifaceted reasons for the current status from the medical, research, and regulatory perspectives are discussed here. In summary, this review presents the scientific background, current state, and implications of clinical mesenchymal stem cell application in the musculoskeletal system and provides perspectives for future developments.

Background The presented prospective randomized controlled single-centre study compares the clinical outcome up to 12 months after total hip arthroplasty using a minimally invasive single-incision direct anterior (DAA) and a direct transgluteal lateral approach. Methods A total of 123 arthroplasties were evaluated utilizing the Harris Hip Score (HHS), the extra short musculoskeletal functional assessment questionnaire (XSFMA), the Short Form 36 (SF-36) health survey, a Stepwatch™ Activity Monitor (SAM), and a timed 25 m foot walk (T25-FW). Postoperative x-ray images after THA were reviewed to determine inclination and stem positioning. Results At final follow-up, the XSFMA functional index scores were 10.3 (anterior) and 15.08 (lateral) while the bother index summed up to a score of 15.8 (anterior) and 21.66 (lateral) respectively, thus only differing significantly for the functional index ( p  = 0.040 and p  = 0.056). The SF-36 physical component score (PCS) was 47.49 (anterior) and 42.91 (lateral) while the mental component score (MCS) summed up to 55.0 (anterior) and 56.23 (lateral) with a significant difference evident for the PCS ( p  = 0.017; p  = 0.714). Patients undergoing THA through a DAA undertook a mean of 6402 cycles per day while those who had undergone THA through a transgluteal approach undertook a mean of 5340 cycles per day ( p  = 0.012). Furthermore, the obtained outcome for the T25-FW with 18.4 s (anterior) and 19.75 s (lateral) and the maximum walking distance (5932 m and 5125 m) differed significantly ( p  = 0.046 and p  = 0.045). The average HHS showed no significant difference equaling 92.4 points in the anterior group and 91.43 in the lateral group ( p  = 0.477). The radiographic analysis revealed an average cup inclination of 38.6° (anterior) and 40.28° (lateral) without signs of migration. Conclusion In summary, our outcomes show that after 1 year THA through the direct anterior approach results in a higher patient activity compared to THA utilizing a transgluteal lateral approach while no differences regarding hip function are evident. Trial registration DRKS00014808 (German Clinical Trial Register DRKS); date of registration: 31.05.2018.

Purpose The development of minimal-incision techniques for total hip replacement with preservation of soft tissue is generally associated with faster rehabilitation, reduction of postoperative pain and increased patient comfort. The aim of this study was to compare a minimal-incision anterior approach with a transgluteal lateral technique for hip replacement surgery with respect to postoperative pain, consumption of rescue medication, length of hospital stay and time to reach a defined range of motion. Methods In this retrospective cohort study we investigated 100 patients with a minimal-incision anterior approach (group I) and 100 patients with a transgluteal lateral approach (group II) retrospectively undergoing unilateral hip replacement. The study variables were pain at rest and during physiotherapy, amount of rescue medication, the time to reach a defined flexion and time in hospital. Results The patients of group I consumed less rescue medication (19.6 ± 6.9 mg vs. 23.6 ± 11.3 mg;   p  = 0.005) and experienced less pain on the day of surgery (1.3 ± 1 vs. 2.3 ± 1.3, p  = 0.0001) and the first postoperative day (0.41 ± 0.8 vs. 0.66 ± 1.1, p = 0.036). The time to reach the defined range of motion (6.4 ± 2 days vs. 7.4 ± 2.1 days; p  = 0.001) and the length of hospital stay were shorter (10.2 ± 1.9 days vs. 13.4 ± 1.6 days; p  = 0.0001) for group I. However, pain during physiotherapy was higher on the third and sixth through ninth days after surgery in comparison to group II ( p  = 0.001–0.013). Conclusion The implantation of a hip prosthesis through a minimal-incision anterior approach is successful in reducing postoperative pain and consumption of pain medication. Time to recovery and length of hospital stay are also influenced positively. Pain increases during physiotherapy, and may be mitigated by adopting limited weight bearing during the early postoperative period.

Purpose The aim of the present study was to compare the daily activity and functionality in a patient cohort 12 months after total hip arthroplasty (THA) using a direct anterior approach with a healthy non-operated control population. Methods Sixty-four patients who underwent THA and 59 healthy individuals (control) were assessed regarding their daily activity and joint functionality utilizing the Harris hip score (HHS), the extra short musculoskeletal functional assessment questionnaire (XSFMA), the Short Form 36 (SF-36) health survey and a Stepwatch™ Activity Monitor (SAM). Post-operative x-ray images after THA were analysed regarding inclination and stem positioning. Results Twelve months after surgery, the average HHS showed no significant difference between both groups equalling 90.7 points in the THA patient group and 90.8 in the healthy volunteer group. The XSFMA functional index scores were 11.0 (THA) and 5.0 (control) while the bother index summed up to a score of 15.3 (THA) and 7.6 (control) respectively thus differing significantly ( p  < 0.001). Daily activity equalled 4227 (THA) and 4687 (control) load cycles per day ( p  = 0.327) while a number of 5658 (THA) and 6417 (control) steps per day ( p  = 0.011) was recorded. The SF-36 physical component scores were 47.3 (THA) and 50.6 (control) points while the psychometric properties added up to a score of 56.1 (THA) and 55.9 (control). The physical component was determined to be significantly different ( p  < 0.001) whereas no statistically significant difference could be shown for the psychometric properties ( p  = 0.511). The radiographic analysis revealed an average cup inclination of 39.9° without signs of migration. Stem positioning was neutral in 53% of all cases while 36% were graded varus and 11% valgus. Conclusion In summary, our short-term results show an activity, functionality and quality of life for patients one year after THA comparable to healthy control individuals.

When ruptured, the anterior cruciate ligament (ACL) of the human knee has limited regenerative potential. However, the goal of this report was to show that the cells that migrate out of the human ACL constitute a rich population of progenitor cells and we hypothesize that they display mesenchymal stem cell (MSC) characteristics when compared with adherent cells derived from bone marrow or collagenase digests from ACL. We show that ACL outgrowth cells are adherent, fibroblastic cells with a surface immunophenotype strongly positive for cluster of differentiation (CD)29, CD44, CD49c, CD73, CD90, CD97, CD105, CD146, and CD166, weakly positive for CD106 and CD14, but negative for CD11c, CD31, CD34, CD40, CD45, CD53, CD74, CD133, CD144, and CD163. Staining for STRO-1 was seen by immunohistochemistry but not flow cytometry. Under suitable culture conditions, the ACL outgrowth-derived MSCs differentiated into chondrocytes, osteoblasts, and adipocytes and showed capacity to self-renew in an in vitro assay of ligamentogenesis. MSCs derived from collagenase digests of ACL tissue and human bone marrow were analyzed in parallel and displayed similar, but not identical, properties. In situ staining of the ACL suggests that the MSCs reside both aligned with the collagenous matrix of the ligament and adjacent to small blood vessels. We conclude that the cells that emigrate from damaged ACLs are MSCs and that they have the potential to provide the basis for a superior, biological repair of this ligament.

Introduction The bursa subacromialis (BS) provides the gliding mechanism of the shoulder and regenerates itself after surgical removal. Therefore, we explored the presence of mesenchymal stem cells (MSCs) within the human adult BS tissue and characterized the BS cells compared to MSCs from bone marrow (BMSCs) on a molecular level. Methods BS cells were isolated by collagenase digest from BS tissues derived from patients with degenerative rotator cuff tears, and BMSCs were recovered by adherent culture from bone-marrow of patients with osteoarthritis of the hip. BS cells and BMSCs were compared upon their potential to proliferate and differentiate along chondrogenic, osteogenic and adipogenic lineages under specific culture conditions. Expression profiles of markers associated with mesenchymal phenotypes were comparatively evaluated by flow cytometry, immunohistochemistry, and whole genome array analyses. Results BS cells and BMSCs appeared mainly fibroblastic and revealed almost similar surface antigen expression profiles, which was CD44 + , CD73 + , CD90 + , CD105 + , CD106 + , STRO-1 + , CD14 − , CD31 − , CD34 − , CD45 − , CD144 − . Array analyses revealed 1969 genes upregulated and 1184 genes downregulated in BS cells vs. BMSCs, indicating a high level of transcriptome similarity. After 3 weeks of differentiation culture, BS cells and BMSCs showed a similar strong chondrogenic, adipogenic and osteogenic potential, as shown by histological, immunohistochemical and RT-PCR analyses in contrast to the respective negative controls. Conclusions Our in vitro characterizations show that BS cells fulfill all characteristics of mesenchymal stem cells, and therefore merit further attention for the development of improved therapies for various shoulder pathologies.

Background To prevent bone loss in hip arthroplasty, several short stem systems have been developed, including the Mayo conservative hip system. While there is a plethora of data confirming inherent advantages of these systems, only little is known about potential complications, especially when surgeons start to use these systems. Methods In this study, we present a retrospective analysis of the patients’ outcome, complications and the complication management of the first 41 Mayo conservative hips performed in 37 patients. For this reason, functional scores, radiographic analyses, peri- and postoperative complications were assessed at an average follow-up of 35 months. Results The overall HHS improved from 61.2 pre-operatively to 85.6 post-operatively. The German Extra Short Musculoskeletal Function Assessment Questionnaire (XSFMA-D) improved from 30.3 pre-operatively to 12.2 post-operatively. The most common complication was an intraoperative non-displaced fracture of the proximal femur observed in 5 cases (12.1%). Diabetes, higher BMI and older ages were shown to be risk factors for these intra-operative periprosthetic fractures ( p  < 0.01). Radiographic analysis revealed a good offset reconstruction in all cases. Conclusion In our series, a high complication rate with 12.1% of non-displaced proximal femoral fractures was observed using the Mayo conservative hip. This may be attributed to the flat learning curve of the system or the inherent patient characteristics of the presented cohort.

Orthopaedic and trauma research is a gateway to better health and mobility, reflecting the ever-increasing and complex burden of musculoskeletal diseases and injuries in Germany, Europe and worldwide. Basic science in orthopaedics and traumatology addresses the complete organism down to the molecule among an entire life of musculoskeletal mobility. Reflecting the complex and intertwined underlying mechanisms, cooperative research in this field has discovered important mechanisms on the molecular, cellular and organ levels, which subsequently led to innovative diagnostic and therapeutic strategies that reduced individual suffering as well as the burden on the society. However, research efforts are considerably threatened by economical pressures on clinicians and scientists, growing obstacles for urgently needed translational animal research, and insufficient funding. Although sophisticated science is feasible and realized in ever more individual research groups, a main goal of the multidisciplinary members of the Basic Science Section of the German Society for Orthopaedics and Trauma Surgery is to generate overarching structures and networks to answer to the growing clinical needs. The future of basic science in orthopaedics and traumatology can only be managed by an even more intensified exchange between basic scientists and clinicians while fuelling enthusiasm of talented junior scientists and clinicians. Prioritized future projects will master a broad range of opportunities from artificial intelligence, gene- and nano-technologies to large-scale, multi-centre clinical studies. Like Prometheus in the ancient Greek myth, transferring the elucidating knowledge from basic science to the real (clinical) world will reduce the individual suffering from orthopaedic diseases and trauma as well as their socio-economic impact.

Explant cultures of adult human trabecular bone fragments give rise to osteoblastic cells, that are known to express osteoblast-related genes and mineralize extracellular matrix. These osteoblastic cells have also been shown to undergo adipogenesis in vitro and chondrogenesis in vivo. Here we report the in vitro developmental potential of adult human osteoblastic cells (hOB) derived from explant cultures of collagenase-pretreated trabecular bone fragments. In addition to osteogenic and adipogenic differentiation, these cells are capable of chondrogenic differentiation in vitro in a manner similar to adult human bone marrow-derived mesenchymal progenitor cells. High-density pellet cultures of hOB maintained in chemically defined serum-free medium, supplemented with transforming growth factor-β1, were composed of morphologically distinct, chondrocyte-like cells expressing mRNA transcripts of collagen types II, IX and X, and aggrecan. The cells within the high-density pellet cultures were surrounded by a sulfated proteoglycan-rich extracellular matrix that immunostained for collagen type II and proteoglycan link protein. Osteogenic differentiation of hOB was verified by an increased number of alkaline phosphatase-positive cells, that expressed osteoblast-related transcripts such as alkaline phosphatase, collagen type I, osteopontin and osteocalcin, and formed mineralized matrix in monolayer cultures treated with ascorbate, β-glycerophosphate, and bone morphogenetic protein-2. Adipogenic differentiation of hOB was determined by the appearance of intracellular lipid droplets, and expression of adipocyte-specific genes, such as lipoprotein lipase and peroxisome proliferator-activated receptor γ2, in monolayer cultures treated with dexamethasone, indomethacin, insulin and 3-isobutyl-1-methylxanthine. Taken together, these results show that cells derived from collagenase-treated adult human trabecular bone fragments have the potential to differentiate into multiple mesenchymal lineages in vitro, indicating their developmental plasticity and suggesting their mesenchymal progenitor nature.

Current approaches for segmental bone defect reconstruction are restricted to autografts and allografts which possess osteoconductive, osteoinductive and osteogenic properties, but face significant disadvantages. The objective of this study was to compare the regenerative potential of scaffolds with different material composition but similar mechanical properties to autologous bone graft from the iliac crest in an ovine segmental defect model. After 12 weeks, in vivo specimens were analysed by X-ray imaging, torsion testing, micro-computed tomography and histology to assess amount, strength and structure of the newly formed bone. The highest amounts of bone neoformation with highest torsional moment values were observed in the autograft group and the lowest in the medical grade polycaprolactone and tricalcium phosphate composite group. The study results suggest that scaffolds based on aliphatic polyesters and ceramics, which are considered biologically inactive materials, induce only limited new bone formation but could be an equivalent alternative to autologous bone when combined with a biologically active stimulus such as bone morphogenetic proteins.