Introduction

Ink engineering can advance 3D-printability for better therapeutics, with optimized proprieties. Herein, we describe a methodology for yielding 3D-printable nanocomposite inks (NC) using low-viscous matrices, via the interaction between the organic and inorganic phases by chemical coupling.

Hip and knee joint arthroplasty wait list has been getting outrageously long in South Africa with some tertiary hospital reporting more than 5 years of waiting time. This has been further compounded by covid 19 pandemic. There is plateau of ideas on how best to address the backlogs in high volume tertiary centers, with catchup list, out reach program, private partnership seeming unsustainable. We sought to look for sustainable solution to the problem and we looked not far but inside the system.

Total Joint Arthroplasty (TJA) is a successful orthopaedic procedure allowing dramatic clinical and functional improvements. Globally, there's been an increase in demand and performed cases associated with an increase in complications. Subsequently, focus on the prevention of complications has become important worldwide. The incidence of venous-thrombolic events (VTE) despite great attention has not diminished despite much investigation. A balance between efficacy and safety from the available agents is essential. Low molecular weight heparin (LMWH) has been commonly used, but oral anti-coagulants have become more popular. The aim of this study was to assess the adherence LMWH and the effectiveness and safety of preventing VTE in post-operative arthroplasty patients in a South African setting.

We conducted a prospective cohort study that included hip and knee, primary and revision, arthroplasty patients who received thromboprophylaxis with one daily injection of LMWH for 14 days post discharge. Patients who omitted 1 or more doses during the follow up period were classified as “non adherent”. A questionnaire was used at follow up visits at least 6 weeks post-operatively.

100 consecutive patients were followed up. The mean age of patients was 63.45 years. There were 68 % female patients. There was a 92% compliance rate. 60 % of patients had the injection administered by a family member, 38 % administered it themselves and 2 % had the injection administered by health professionals. Venous thromboembolic events were confirmed in 5 % at 7.86 days after surgery. Three patients had persistent wound drainage after surgery, however, none required reoperation or readmission.

Compliance with LMWH is high and is comparable with oral agents. It is effective in preventing VTE and safe with regards to bleeding and wound complications in a South African setting. Patient education regarding medications may improve compliance of the medication.

Tendon-to-bone multi-tissue transition exhibits a hierarchical and continuous gradient of matrix composition and alignment, allowing for efficient transmission of mechanical loading between tendon and bone. Upon injury, main problems associated with tendon-to-bone regeneration include disorganized matrix deposition, with a gradual loss of mineral content resulting in poor mechanical properties, limiting tissue integration and the formation of a graded interface. Therefore, we propose to assembly two types of continuous microfibres with distinct topological and compositional features tailored to guide cell alignment and matrix deposition while matching the mechanical requirements of the native tissue.

Wet-spinning was used to produce textured composite microfibres using different flow rates and two polymer blends to replicate the anisotropic architecture of tendon (PCL/Gelatin, 22/9%, w/v) and the isotropic organization together with mineral composition of bone (PCL/Gelatin/Hydroxyapatite, 22/9% w/v and 7.7% w/w HAp). Obtained microfibres morphology, chemical and mechanical properties were evaluated. Biological performance was studied using human adipose-derived stem cells (hASCs). Cytoskeleton alignment, nuclei elongation and matrix mineralization were evaluated. Textile techniques were used to create a 3D fibrous scaffold. Morphological features were analyzed by micro-CT.

PCL/Gelatin fibers produced at 1 mL/h extrusion rate exhibited the highest anisotropic alignment, in opposition to PCL/Gelatin/HAp fibers produced under the same condition. Micro-CT analysis of PCL/Gelatin/HAp fibers demonstrated variations within pore diameter and particles size between the different flow rates. Herein, PCL/Gelatin fibers induced a higher cytoskeleton alignment and nuclei elongation (p < 0.0001) in seeded hASCs. In contrast, significantly higher mineralization was found in PCL/Gelatin/HAp fibres (day 7, p < 0.04; day 14, p < 0.0001) as observed by alizarin red staining and quantification, suggesting the induction of an osteogenic-like phenotype. As proof of concept, textile techniques were used to assemble the two types of fibers and create a 3D scaffold presenting a continuous gradient in HAp content, as well as topological cues. After 14 days of culture with hASCs, a gradient of collagen deposition and matrix mineralization was found (p < 0.014, p < 0.0001). Higher deposition of collagen type II was observed in the tendon and interface parts of the fibrous scaffold and collagen type X in the interface.

Overall, the wet-spinning method was efficiently used to engineer continuous textured composite microfibers. PCL/Gelatin fibers supported cell alignment mimicking tendon one, while PCL/Gelatin/HAp fibers induced mineral deposition and a possible phenotypic change without additional medium supplementation. Textile techniques allowed fibres assemblage and 3D scaffolds fabrication envisioning tendon-to-bone applications.

Tendon injuries constitute a major healthcare burden owing to the limited healing ability of these tissues and the poor clinical outcomes of surgical repair treatments. Recent advances in tendon tissue engineering (TTE) strategies, particularly through the use of biotextile technologies, hold great promise toward the generation of artificial living tendon constructs. We have previously developed a braided construct based on suture threads coated with gelMA:alginate hydrogel encapsulating human tendon cells. These cell-laden composite fibers enabled the replication of cell and tissue-level properties simultaneously. Based on this concept, in this study we explored the use of platelet lysate (PL), a pool of supra-physiological concentrations of growth factors (GFs), to generate a hydrogel layer, which is envisioned to act as a depot of therapeutic factors to induce tenogenic differentiation of encapsulated human adipose stem cells (hASCs). For this purpose, commercially available suture threads were first embedded in a thrombin solution and then incubated in PL containing hASCs. Herein, thrombin induces the gelation of PL and consequent hydrogel formation. After coating suture threads with the mixture of PL-ASCs, cells were found to be viable and homogeneously distributed along the fibers. Strikingly, hASCs encapsulated within the PL hydrogel layer around the suture thread were able to sense chemotactic factors present in PL and to establish connections between adjacent independent fibers, suggesting a tremendous potential of PL cell-laden hydrogel fibers as building blocks in the development of living constructs aimed at tendon repair applications.

Tendon detachment from its bony insertion is one of the most frequent injuries occurring in the musculoskeletal interface, constituting an unmet challenge in orthopaedics. Tendon-to-bone integration occurs at the enthesis, which is characterized by a complex structure organized in a gradient of cells and microenvironments. Hence, the maintenance of a heterotypic cellular niche is critical for tissue functionality and homeostasis. Replicating this unique complexity constitutes a challenge when addressing tendon-to-bone regeneration and interfacial tissue engineering strategies. Currently, mechanisms presiding to tendon-to-bone interface healing are not yet fully understood, particularly the interactions between tendon and bone cells in the orchestration of interfacial repair versus regeneration. Therefore, this study focused on the hypothesis that interactions between human tendon-derived cells (hTDCs) and pre-osteoblasts (pre-OB) can initiate a cascade of events, potentially leading to interfacial regeneration. Thus, hTDCs and pre-OB (pre-differentiated human adipose-derived stem cells) were used. Herein, five different ratios between basal and osteogenic media (100:0,75:25,50:50,25:75,0:100) were assessed to estimate their influence on cell behaviour and identify the ideal parameters for simultaneously supporting tenogenic and osteogenic differentiation before establishing a co-culture. Tenogenic and osteogenic differentiation were assessed through the expression of tendon and bone markers, mineralization (alizarin red, AZ) and alkaline phosphatase (ALP) quantification. Results showed that hTDCs exhibited osteogenic differentiation potential when cultured in the presence of osteogenic media, as demonstrated by an increase in ALP activity and mineralization. Pre-OB expressed osteogenic markers (OCN, OPN) in all media conditions confirming osteogenic commitment, which was simultaneously confirmed by ALP levels and AZ staining. Thus, three different conditions (100:0, 50:50, 0:100) were chosen for further studies in a direct contact co-culture system. Similarly to single cultures, a significant proliferation was observed in all conditions and mineralization was increased as soon as 7 days of culture. Additionally, osteogenic, tenogenic and interface-relevant markers will be assessed to study the effect of co-culture on phenotype maintenance. In summary, the present work addresses major limitations to clinical translation of cell-based therapies aiming at promoting interfacial regeneration. Particularly, we explored the influence of culture media on the maintenance of tenogenic and osteogenic niches, taking a basic and critical step towards the establishment of more complex cell-based systems.

Acknowledgements

Authors thank Fundação para a Ciência e Tecnologia in the framework of FCT-POPH-FSE, SFRH/BD/96593/2013 (RCA) and IF/00593/2015 (MEG); and to FCT/MCTES and the FSE/POCH, PD/59/2013 for PD/BD/128088/2016 (IC).

Pyogenic spondylodiscitis is an uncommon but clinically relevant infection that represents 3 to 5% of all cases or osteomyelitis. In Europe, it has an estimated incidence of 0.4 to 2.4/100.000 people/year. Mortality is less than 5%, increasing with a delay in diagnosis greater than 2 month. Patients with renal failure have greater predisposition to infections, consequence of the chronic uremic state. Infection rates in Polytetrafluoroethylene (PTFE) hemodialysis grafts in end-stage renal disease (ESRD) range from 3 to 35%. We present a rare case of concurrent spondylodiscitis and PTFE graft infection in a patient with ESRD and recurrent urinary tract infections (RUTI).

The authors present a case of an 80-year-old man with past medical history significant for abdominal aortic aneurysm, bilateral ureter-hydronephrosis, Pseudomonas aeruginosa RUTI and ESRD. Three months after a dialysis PTFE graft hemoaccess was performed a Pseudomonas graft infection was diagnosed and the PTFE graft was removed. One week later, the patient was observed in the author's Department due to an insidious dorsal-lumbar mechanic back pain without neurologic deficits, with progressive deterioration over the past 6 months. A T12-L1 and L1-L2 spondylodiscitis with dural compression was diagnosed and vertebral instability was documented on MRI and TC, demanding surgical treatment. Instrumented fusion with a screw and rod construct was performed from T9 to L5, along with somatic L1 and L2 debridement, and T12-L1 interbody fusion with autograft. Microbiology results were positive for Pseudomonas aeruginosa. Antibotic therapy with ceftazidime (6 weeks) and ciprofloxacin (12 weeks) was performed. Symptomatic relieve was achieved and C-reactive protein and white blood cell count returned to normal values.

No complications were documented. Four months post-surgery, the patient was asymptomatic (Visual Analogue Scale=0), with no significant limitation in his daily life activity (Disability Rating Index=85) and the vertebral body height was sustained, with imagiological signs of spinal fusion.

ESRD patients are more susceptive to infections. Failure in early diagnosis and treatment may lead to disease progression and subsequent functional limitations, deformity and increase in mortality. An aggressive approach, despite delay on diagnosis, is the key factor for a worthy outcome.

Despite the good results, recrudescence of spondylodiscitis is known to occur even years after the original offense is treated.

To report a rare case of successfully treated synchronous shoulder septic arthritis, total knee replacement infection and lumbar spondylodiscitis in a patient with rheumatoid arthritis.

Fifty-six year old woman, with a history of rheumatoid arthritis diagnosed at twenty-five year old, and total knee replacement at fifty-four. Recently treated with etanercept, presented with acute inflammatory signs of the right shoulder in addition to right knee and lumbar back pain for 6 months. After a shoulder and knee arthrocentesis the diagnosis suspicion of shoulder septic arthritis and total knee replacement infection was confirmed. Therefore it was performed shoulder arthroscopic irrigation and debridement and the first of two stages knee revision, with implantation of antibiotic cement on cement articulating spacer. It was also diagnosed a L1–L2 and L4–L5 spondylodiscitis with dural compression documented on MRI, which determined surgical treatment. By a posterior approach it was performed instrumentation from T11 to L5, followed by L1–L2 and L4–L5 discectomy and interbody fusion with autograft. Shoulder and knee synovial fluid cultures where positive for Methicillin Sensible Staphylococcus aureus narrowing the broad-spectrum combination therapy to levofloxacin for six weeks, with symptomatic relieve and C-reactive protein and white blood cell count returning to normal values.

Almost one year down the line the patient remained with no sign of infection, even under the influence of immunosuppressive therapeutic. She returned to her previous status concerning the rheumatologic disease and the second stage knee revision is being planned to happen on the short run.

Rheumatoid arthritis patients are a high-risk group for septic arthritis considering, among others, the immunosuppressive therapeutics and the frequent history of arthroplasty. The presented case illustrates three different type of septic complication in the same patient. The timely and aggressive approach was the key factor for a good outcome.