Objective. To analyze the short-term outcome after medial open-wedge high tibial osteotomy with a 3D-printing technology in early medial keen osteoarthritis and varus malalignment. Design and Method. 32 knees(28 cases) of mOWHTO (fixation with an angular-stable TomoFix implant(Synthes)) with a 3D-printing technology combined with arhtroscopy were prospectively surveyed with regard to functional outcome(Hospital for special knee score [HSS] score). Pre- and postoperative tibial bone varus angle (TBVA), mechanical medial proximal tibial angle (MPTA), and alignment were analyzed with regard to the result. Results. 32 knees were included (28 patients; mean age 46.5±9.3 years). The follow-up rate was 100% at 1.7±0.6 years (range, 1.2–3.2 years). Pre- and postoperative mechanical tibiofemoral axis were 6.8°±2°of varus and 1.2°± 3.4° of valgus, respectively. HSS score significantly improved from 46.0±18.3 preoperatively to 84±12 at one, 80±7 at two years (P<0.01). Conclusions. Medial open-wedge high tibial osteotomy with a 3D-printing technology combined with arthroscopy in medial keen osteoarthritis and varus malalignment is an accurate and good treatment option. High preoperative TBVA and appropriate corrected angle(0–3° of valgus)) was associated with better functional outcome at final follow-up

Reconstructing mandibular and maxillary bone defects with free vascularized bone flaps requires to take into account the aesthetic and functional requirements to consider subsequent placement of dental implants. It implies a three-dimensional conformation of the bone fragment. This is usually done by making osteotomies on the bone harvested. The aim of our study was to evaluate the interest of virtual planning and 3D printing using free software and a consumer printer in this indication.

Invesalius® software (Technology of Information Renato Archer Center, Campinas, Brazil) was used to build virtual models from the patients' CT scan imaging data. The surgical procedure was planned using Meshmixer® (Autodesk, San Rafael, United States). Meshlab® software (Visual Computing Lab, Pisa, Italy) was used to design cutting guides for the flap harvest and modelling. 3D printing of these guides with a consumer printer (Ultimaker 2® Ultimaker B.V., Geldermalsen, the Netherlands) allowed the transfer of the planning to the operating room.

Three patients requiring mandibular reconstruction underwent an iliac crest free flap, a fibula free flap and a scapula free flap, and could benefit from this technique. In each case, the bone resection was performed virtually and the positioning of the bone available at the donor site was simulated on screen. This allowed to anticipate the position and orientation of the cutting planes on the bone flap. From the anatomy of the donor site and the cutting planes, harvest templates and cutting guides could be designed by computer. Planning the conformation of the bone flap to the recipient site has allowed an anatomical, aesthetic and functional reconstruction of the bone defect.

Surgeon-made virtual planning and “low cost” 3D printing helps harvest the bone flap and position and orient the osteotomies to adapt it to the defect. They provide, both the patient and the surgeon, reduced operative time and better anticipation of the result, particularly in the context of the maxillofacial reconstruction. Compared to commercially available custom-made devices, this technique allows the manufacture of the guides without delay and at a cheap price.

Paediatric musculoskeletal (MSK) disorders often produce severe limb deformities, that may require surgical correction. This may be challenging, especially in case of multiplanar, multifocal and/or multilevel deformities. The increasing implementation of novel technologies, such as virtual surgical planning (VSP), computer aided surgical simulation (CASS) and 3D-printing is rapidly gaining traction for a range of surgical applications in paediatric orthopaedics, allowing for extreme personalization and accuracy of the correction, by also reducing operative times and complications. However, prompt availability and accessible costs of this technology remain a concern. Here, we report our experience using an in-hospital low-cost desk workstation for VSP and rapid prototyping in the field of paediatric orthopaedic surgery. From April 2018 to September 2022 20 children presenting with congenital or post-traumatic deformities of the limbs requiring corrective osteotomies were included in the study. A conversion procedure was applied to transform the CT scan into a 3D model. The surgery was planned using the 3D generated model. The simulation consisted of a virtual process of correction of the alignment, rotation, lengthening of the bones and choosing the level, shape and direction of the osteotomies. We also simulated and calculated the size and position of hardware and customized massive allografts that were shaped in clean room at the hospital bone bank. Sterilizable 3D models and PSI were printed in high-temperature poly-lactic acid (HTPLA), using a low-cost 3D-printer. Twenty-three operations in twenty patients were performed by using VSP and CASS. The sites of correction were: leg (9 cases) hip (5 cases) elbow/forearm (5 cases) foot (5 cases) The 3D printed sterilizable models were used in 21 cases while HTPLA-PSI were used in five cases. customized massive bone allografts were implanted in 4 cases. No complications related to the use of 3D printed models or cutting guides within the surgical field were observed. Post-operative good or excellent radiographic correction was achieved in 21 cases. In conclusion, the application of VSP, CASS and 3D-printing technology can improve the surgical correction of complex limb deformities in children, helping the surgeon to identify the correct landmarks for the osteotomy, to achieve the desired degree of correction, accurately modelling and positioning hardware and bone grafts when required. The implementation of in-hospital low-cost desk workstations for VSP, CASS and 3D-Printing is an effective and cost-advantageous solution for facilitating the use of these technologies in daily clinical and surgical practice

Intervertebral disc degeneration can lead to physical disability and significant pain, while the present therapeutics still fail to biochemically and biomechanically restore the tissue. Stem cell-based therapy in treating intervertebral disc (IVD) degeneration is promising while transplanting cells alone might not be adequate for effective regeneration. Recently, gene modification and 3D-printing strategies represent promising strategies to enhanced therapeutic efficacy of MSC therapy. In this regard, we hypothesized that the combination of thermosensitive chitosan hydrogel and adipose derived stem cells (ADSCs) engineered with modRNA encoding Interleukin − 4 (IL-4) can inhibit inflammation and promote the regeneration of the degenerative IVD. Rat ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IL-4 modRNA engineered ADSCs (named as IL-4-ADSCs) on nucleus pulposus cells. ModRNA transfected mouse ADSCs with high efficiency and the IL-4 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IL-4 protein. In vitro, IL-4-ADSCs induced increased anabolic markers expression of nucleus pulposus cells in inflammation environment compared to untreated ADSCs. These findings collectively supported the therapeutic potential of the combination of thermosensitive chitosan hydrogel and IL-4-ADSCs for intervertebral disc degeneration management. Histological and in vivo validation are now being conducted

In the field of tissue engineering (TE), mainly two approaches have been widely studied and utilised throughout the last two decades. Ovsianikov et al. proposed a third strategy for tissue engineering to combine the advantages of the scaffold-based and scaffold-free approach [1]. We utilise the third strategy for TE by fabrication of cell spheroids that are reinforced by microscaffolds, called tissue units (TUs). Aim of the presented study is to differentiate TUs towards a chondrogenic phenotype to show the self-assembly of a millimetre sized cartilage-like tissue in a bottom-up TE approach in vitro. Two-Photon polymerization (2PP) was utilised to fabricate highly porous microscaffolds with a diameter of 300 µm. The biocompatible and biodegradable, resin Degrad INX (supplied from Xpect INX, Ghent, Belgium) was used for 3D-printing. Each microscaffold was seeded with 4000 human adipose derived stem cells (hASCs) in low-adhesive 96-well plates to allow spheroid formation. TUs were differentiated towards the chondrogenic lineage by application of chondrogenic media, subsequently merged in a cylindrical agarose mold, to fuse into a connected tissue with a diameter of ~1.8 mm and a height of 8 mm. The characterization of TUs differentiated towards the chondrogenic phenotype included gene expression and protein analysis. Furthermore, immunohistochemically staining for Collagen II and Alcian blue staining were performed to investigate the matrix deposition and fusion of the self-assembled tissue. Our results suggest that the utilised method could be a promising approach for a variety of tissue engineering approaches, due to the good applicability to a defect side combined with the self-assembly properties of the TUs. Furthermore, the differentiation potential of hASCs is not limited to chondrogenic lineages only, which could pave the way to further TE applications in the future. Acknowledgements:. This research work was financially supported by the European Research Council (Consolidator Grant 772464 A.O.)

To design slow resorption patient-specific bone graft whose properties of bone regeneration are increased by its geometry and composition and to assess it in in-vitro and in-vivo models. A graft composed by hydroxyapatite (HA) and β-TCP was designed as a cylinder with 3D gyroid porosities and 7 mm medullary space based on swine's anatomy. It was produced using a stereolithography 3D-printing machine (V6000, Prodways). Sterile bone grafts impregnated with or without a 10µg/mL porcine BMP-2 (pBMP-2) solution were implanted into porcine femurs in a bone loss model. Bone defect was bi-weekly evaluated by X-ray during 3 months. After sacrifice, microscanner and non-decalcified histology analysis were conducted on biopsies. Finally, osteoblasts were cultured inside the bone graft or in monolayer underneath the bone graft. Cell viability, proliferation, and gene expression were assessed after 7 and 14 days of cell culture (n=3 patients). 3D scaffolds were successfully manufactured with a composition of 80% HA and 20% β-TCP ±5% with indentation compressive strength of 4.14 MPa and bending strength of 11.8MPa. In vivo study showed that bone regeneration was highly improved in presence of pBMP-2. Micro-CT shows a filling of the gyroid sinuses of the implant (Figure 1). In vitro, the presence of BMP2 did not influence the viability of the osteoblasts and the mortality remained below 3%. After 7 days, the presence of BMP2 in the scaffold significantly increased by 85 and 65% the COL1A1 expression and by 8 and 33-fold the TNAP expression by osteoblasts in the monolayer or in the scaffold, respectively. This BMP2 effect was transient in monolayer and did not modify gene expression at day 14. BMP2-impregnated bone graft is a promising patient-personalized 3D-printed solution for bone defect regeneration, by promoting neighboring host cells recruitment and solid new bone formation. For any figures and tables, please contact the authors directly

Since the development of biomimetic and ceramic bone reconstructive in the early 1970, these specialised bioreactors intended for bone or cartilage regeneration have come a long way in trying to design an alternative procedure other than autogenous bone grafting. However, all known biomaterials still fall short of inducing substantial bone formation in vitro or in vivo, especially when treating large bony defects. As such there is a necessity to develop novel bone-reconstructive biomaterials that can more appropriately be utilised and can induce substantial more bone formation than current scaffolds. Using the rapid prototyping technique (Friedrich-Baur BioMed Center, Bayreuth, Germany) to develop new and improved hydroxyapatite/β-tricalcium phosphate devices, which can be predesigned to any outer shape with controlled pore structure and exhibit a unique intrinsic porosity <150µm due to the 3D-printing process to fit any skeletal bone loss site, the aim of our laboratories was to test the osteoinductive capacity of these new bioreactors in an in vitro culture system utilising adipose-derived stem cells (ADSCs). Immunofluorescent staining revealed that beside the standard surface protein expression patterns typical for ADSCs, the cells also produced osteoblast specific proteins, specifically osteocalcin, osteopontin and dentin matrix acidic phosphoprotein 1. ADSCs seeded on the surface of the biomimetic scaffolds showed constant proliferation, maintained viability and differentiation throughout the scaffold, including the small intrinsic pores. Subsequent, qRT-PCR also revealed that alkaline phosphatase and osteocalcin expression was significantly increased upon addition of osteogenic medium but even more so when human recombinant morphogenetic protein 2 (hBMP-2) was included. Immunofluorescent data of protein expression was consistent with qRT-PCR data. Taken into account with previous results by our laboratories in respect to adipose tissue as a viable inductive medium that can form substantial new bone formation in vivo the present results demonstrated that the investigated bioceramic devices possess the necessary capacity that could, together with adipose tissue, provide the next leap necessary to finally and decisively induce substantial or total new bone formation in clinical bone defects of humans

Total ankle replacement (TAR) is the main surgical option in case of severe joint osteoarthritis. The high failure rate of current TAR is often associated to inappropriate prosthetic articulating surfaces designed according to old biomechanical concepts such the fixed axis of rotation, thus resulting in non-physiological joint motion. A recent image-based 3D morphological study of the normal ankle (Siegler et al. 2014) has demonstrated that the ankle joint surfaces can be approximated by a saddle-shaped cone with its apex located laterally (SSCL). We aimed at comparing the kinematic effects of this original solution both with the intact joint and with the traditional prosthetic articulating surfaces via in-silico models and in-vitro measurements. Native 3D morphology of ten normal cadaver ankle specimens was reconstructed via MRI and CT images. Three custom-fit ankle joint models were then developed, according to the most common TAR designs: cylindrical, symmetrically-truncated medial apex cone (as in Inman's pioneering measures), and the novel lateral apex cone, i.e. SSCL. Bone-to-bone motion, surface-to-surface distance maps, and ligament forces and deformations were evaluated via computer simulation. Prototypes of corresponding prosthesis components were designed and manufactured via 3D-printing, both in polymer-like-carbon and in cobalt-chromium-molybdenum powders, for in-vitro tests on the cadaver specimens. A custom testing rig was used for application of external moments to the ankle joint in the three anatomical planes; a motion tracking system with trackers pinned into the bone was used to measure tibial, talar and calcaneal motion (Franci et al. 2009), represented then as tibiotalar, subtalar and ankle complex 3D joint rotations. Each ankle specimen was tested in the intact joint configuration and after replacement of the articulating surfaces according with the three joint models: cylindrical, medial apex cone and SSCL. Results. Small intra-specimen data variability in cycle-to-cycle joint kinematics was found in all cadaver ankles, the maximum standard deviation of all rotation patterns being smaller than 2.0 deg. In-silico ligament strain/stress analysis and in-vitro joint kinematic and load transfer measurements revealed that the novel SSCL surfaces reproduce more natural joint patterns than those with the most common surfaces used in current TAR. TAR based on a saddle-shaped skewed truncated cone with lateral apex is expected to restore more normal joint function. Additional tests are undergoing for further biomechanical validation. The present study has also demonstrated the feasibility and the quality of the full process of custom TAR design and production for any specific subject. This implies a thorough procedure, from medical imaging to the production of artificial surfaces via 3D printing, which is allowing for personalised implants to become the future standard in total joint replacement

The management of maxillofacial injuries requires restoring the contours of the facial skeleton to achieve an aesthetic outcome. When fractures are simple, open reduction and rigid fixation with stock titanium osteosynthesis plates is usually sufficient. However, when the damage is more substantial (when the fracture is comminuted or in case of a bone defect) anatomical landmarks are lost and the reconstruction requires the use of titanium meshes. These meshes are usually modelled intraoperatively to restore the contours of the bone. This can be a tough and time consuming task in case of minimal invasive approach and intraoperative edema. When the injury is unilateral, printing a 3D anatomical model of the mirrored unaffected side is an easy way to accurately pre-bend the mesh preoperatively. With the emergence of “low cost” consumer 3D printers, the aim of our study was to evaluate the cost of this technique in a department of maxillofacial surgery. The first part of the study was to evaluate free software solutions available online to determine which of these could be used to create 3D virtual models from the patients' volume imaging data, mirror the model and export an STL file suitable for 3D-printing with a consumer 3D-printer. The second part was to identify the desktop 3D-printers commercially available according to the different technology used, their prices and that of consumables required. Five free software solutions were identified to create STL meshes of the patient's anatomy from thin slice CT scan DICOM data. Two more were available to repair, segment and mirror them to provide a clean STL file suitable for 3D printing with a desktop 3D printer. The prices of 2 different printers were then listed for each of the 3 additive manufacturing technologies available to date. Prices ranged from 2,299 € for the Ultimaker 2+© (Fuse Deposition Modeling, FDM), to 4,999 € for the Sintratec© printer (Selective Laser Sintering, SLS), the Formlabs 2© (stereolithography) being at an intermediate price of 3,299 €. Finally, the cost of the manufacture of a model was calculated for each of these printers. Considering a model of a supraorbital ridge printed to restore the anterior wall of the frontal sinus, the volume of the mesh is around 20 cm. 3. This represents a cost of less than 1 € with the FDM technology, 4.70 € with stereolithography and 1.50 € with the SLS printer. Since patents of additive manufacturing have become part of the public domain, the cost of 3D printing technology has fallen drastically. Desktop printers are now an investment accessible to a surgery department and the cost of the material is low. This allows the surgeons, by the mean of free software, to directly create 3D models of their patients' anatomy, mirror them if needed and manufacture a template to pre-bend titanium meshes that will be subsequently sterilized for the surgery. Having the printer in the department reduces manufacturing lead times and makes this technique possible even for urgent cases