In vivo characterization of 3D-printed polycaprolactone-hydroxyapatite scaffolds with Voronoi design to advance the concept of scaffold-guided bone regeneration

Three-dimensional (3D)-printed medical-grade polycaprolactone (mPCL) composite scaffolds have been the first to enable the concept of scaffold-guided bone regeneration (SGBR) from bench to bedside. However, advances in 3D printing technologies now promise next-generation scaffolds such as those with Voronoi tessellation. We hypothesized that the combination of a Voronoi design, applied for the first time to 3D-printed mPCL and ceramic fillers (here hydroxyapatite, HA), would allow slow degradation and high osteogenicity needed to regenerate bone tissue and enhance regenerative properties when mixed with xenograft material. We tested this hypothesis in vitro and in vivo using 3D-printed composite mPCL-HA scaffolds (wt 96%:4%) with the Voronoi design using an ISO 13485 certified additive manufacturing platform. The resulting scaffold porosity was 73% and minimal in vitro degradation (mass loss <1%) was observed over the period of 6 months. After loading the scaffolds with different types of fresh sheep xenograft and ectopic implantation in rats for 8 weeks, highly vascularized tissue without extensive fibrous encapsulation was found in all mPCL-HA Voronoi scaffolds and endochondral bone formation was observed, with no adverse host-tissue reactions. This study supports the use of mPCL-HA Voronoi scaffolds for further testing in future large preclinical animal studies prior to clinical trials to ultimately successfully advance the SGBR concept

A surgical Implant: An Apparatus/Method for human long bone reconstruction using bioresorbable bone void fillers consisting of fixtures for modular assembly produced by fused deposition modelling.

The present disclose relates to modular surgical implants, which can be used in treating long bone defect. In particular, the disclosure relates to a surgical implant modular assembly comprising at least a first scaffold and a second scaffold, wherein the first and the second scaffolds are identical

Clinical translation of a patient-specific scaffold-guided bone regeneration concept in four cases with large long bone defects

Background: Bone defects after trauma, infection, or tumour resection present a challenge for patients and clinicians. To date, autologous bone graft (ABG) is the gold standard for bone regeneration. To address the limitations of ABG such as limited harvest volume as well as overly fast remodelling and resorption, a new treatment strategy of scaffold-guided bone regeneration (SGBR) was developed. In a well-characterized sheep model of large to extra-large tibial segmental defects, three-dimensional (3D) printed composite scaffolds have shown clinically relevant biocompatibility and osteoconductive capacity in SGBR strategies. Here, we report four challenging clinical cases with large complex posttraumatic long bone defects using patient-specific SGBR as a successful treatment. Methods: After giving informed consent computed tomography (CT) images were used to design patient-specific biodegradable medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP, 80:20 ​wt%) scaffolds. The CT scans were segmented using Materialise Mimics to produce a defect model and the scaffold parts were designed with Autodesk Meshmixer. Scaffold prototypes were 3D-printed to validate robust clinical handling and bone defect fit. The final scaffold design was additively manufactured under Food and Drug Administration (FDA) guidelines for patient-specific and custom-made implants by Osteopore International Pte Ltd. Results: Four patients (age: 23–42 years) with posttraumatic lower extremity large long bone defects (case 1: 4 ​cm distal femur, case 2: 10 ​cm tibia shaft, case 3: complex malunion femur, case 4: irregularly shaped defect distal tibia) are presented. After giving informed consent, the patients were treated surgically by implanting a custom-made mPCL-TCP scaffold loaded with ABG (case 2: additional application of recombinant human bone morphogenetic protein-2) harvested with the Reamer-Irrigator-Aspirator system (RIA, Synthes®). In all cases, the scaffolds matched the actual anatomical defect well and no perioperative adverse events were observed. Cases 1, 3 and 4 showed evidence of bony ingrowth into the large honeycomb pores (pores >2 ​mm) and fully interconnected scaffold architecture with indicative osseous bridges at the bony ends on the last radiographic follow-up (8–9 months after implantation). Comprehensive bone regeneration and full weight bearing were achieved in case 2 ​at follow-up 23 months after implantation. Conclusion: This study shows the bench to bedside translation of guided bone regeneration principles into scaffold-based bone tissue engineering. The scaffold design in SGBR should have a tissue-specific morphological signature which stimulates and directs the stages from the initial host response towards the full regeneration. Thereby, the scaffolds provide a physical niche with morphology and biomaterial properties that allow cell migration, proliferation, and formation of vascularized tissue in the first one to two months, followed by functional bone formation and the capacity for physiological bone remodelling. Great design flexibility of composite scaffolds to support the one to three-year bone regeneration was observed in four patients with complex long bone defects. The translational potential of this article: This study reports on the clinical efficacy of SGBR in the treatment of long bone defects. Moreover, it presents a comprehensive narrative of the rationale of this technology, highlighting its potential for bone regeneration treatment regimens in patients with any type of large and complex osseous defects.</p

The development of a modular design workflow for 3D printable bioresorbable patient-specific bone scaffolds to facilitate clinical translation

A streamlined design workflow that facilitates the efficient design and manufacture of patient-specific scaffolds independently applied by the surgical team has been recognised as a key step in a holistic approach towards the envisioned routine clinical translation of scaffold-guided bone regeneration (SGBR). A modular design workflow was developed to semi-automatically fill defect cavities, ensure patient specificity and ideal surgical scaffold insertion for a given surgical approach, add fixation points to secure the scaffolds to the host bone and generate scaffold based on Voronoi, periodic lattice and triply periodic minimal surface pore architectures. The adopted functional representation modelling technique produces models free from 3D printing mesh errors. It was applied to a clinical case of a complicated femoral bone defect. All models were free from mesh errors and the patient-specific fit and unobstructive insertion were validated via digital inspection and physical investigation by way of 3D printed prototypes. The real-time responsiveness of the workflow to user input allows the designer to receive real-time feedback from the surgeon, which is associated with reducing the time to finalise a patient-specific scaffold design. In summary, an efficient workflow was developed that substantially facilitates routine clinical implementation of SGBR through its ability to streamline the design of 3D printed scaffolds</p

Design and Development of a Novel Oral Care Simulator for the Training of Nurses

Objective: A Novel Oral Care Simulator was designed and developed to measure and visualise the facial and lingual forces exerted on teeth by the action of tooth brushing, considering the irregular geometry and structural composition of human dentition and the emulation of the realistic biomechanical deflection of the teeth. Method: FEA simulations were carried out on a central incisor under facial loading and an appropriate force sensing mechanism was designed. An anatomically accurate mandibular jaw and 16 teeth were 3D printed, on which 16 force sensing structures were embedded. The signals from the sensors were amplified using a multichannel signal amplifier built using instrumentation amplifiers which were then visualised through a GUI. Results: The developed simulator is capable of indicating the magnitude of a force upto 15 N exerted on to the facial and lingual surfaces of teeth at a frequency of 60 Hz and above and it is capable of alerting the user if the force exceeds a pre-specified threshold. Conclusion: The designed force sensing mechanism considers the irregular geometry and structural composition of human dentition in measuring the facial and lingual forces. It provides a reliable feedback by indicating the force and emulating the realistic biomechanical deflection of teeth. Significance: Nurses who care for the disabled, elderly and sick have explicitly stated the requirement for a simulator to train themselves on brushing the teeth of their subjects as their incorrect technique can cause longterm dental damage, for which a device has not been developed to date.</p

The development of a modular design workflow for 3D printable bioresorbable patient-specific bone scaffolds to facilitate clinical translation

A streamlined design workflow that facilitates the efficient design and manufacture of patient-specific scaffolds independently applied by the surgical team has been recognised as a key step in a holistic approach towards the envisioned routine clinical translation of scaffold-guided bone regeneration (SGBR). A modular design workflow was developed to semi-automatically fill defect cavities, ensure patient specificity and ideal surgical scaffold insertion for a given surgical approach, add fixation points to secure the scaffolds to the host bone and generate scaffold based on Voronoi, periodic lattice and triply periodic minimal surface pore architectures. The adopted functional representation modelling technique produces models free from 3D printing mesh errors. It was applied to a clinical case of a complicated femoral bone defect. All models were free from mesh errors and the patient-specific fit and unobstructive insertion were validated via digital inspection and physical investigation by way of 3D printed prototypes. The real-time responsiveness of the workflow to user input allows the designer to receive real-time feedback from the surgeon, which is associated with reducing the time to finalise a patient-specific scaffold design. In summary, an efficient workflow was developed that substantially facilitates routine clinical implementation of SGBR through its ability to streamline the design of 3D printed scaffolds

Mechanical and geometrical study of 3D printed Voronoi scaffold design for large bone defects

The Voronoi design was utilized for a biodegradable patient-specific bone scaffold with macro pores (>4 mm) for the surgical treatment of a critical-sized bone defect. We have focused on the relationship between scaffold design and mechanical properties. Through a combination of experiments and simulations and have presented morphological and mechanical property maps of scaffold designs based on the Voronoi tessellation. Fused filament fabrication (FFF) was explored as the method of fabrication and prototypes were printed in commercial grade Polylactic Acid (PLA). The subsequent in-silico morphology assessment revealed that the pore sizes ranged from 4.0 to 11.8 mm with a total porosity of 71%. The morphological maps capture the distinct geometry shift between as-designed and as-manufactured scaffolds with an average agreement of 76% where most of the deviations were caused by complications innate to 3D printing. Finite element method models were developed to evaluate mechanical properties and the failure locations of the scaffold were accurately predicted, which was validated by the subsequent quasi-static compression test. This study revealed the potential of the Voronoi tessellation to design patient specific bone scaffolds with macro pore sizes that mimic trabecular bone geometry and concluded that FFF is a suitable method of fabrication for it.</p

In vivo characterization of 3D-printed polycaprolactone-hydroxyapatite scaffolds with Voronoi design to advance the concept of scaffold-guided bone regeneration

Three-dimensional (3D)-printed medical-grade polycaprolactone (mPCL) composite scaffolds have been the first to enable the concept of scaffold-guided bone regeneration (SGBR) from bench to bedside. However, advances in 3D printing technologies now promise next-generation scaffolds such as those with Voronoi tessellation. We hypothesized that the combination of a Voronoi design, applied for the first time to 3D-printed mPCL and ceramic fillers (here hydroxyapatite, HA), would allow slow degradation and high osteogenicity needed to regenerate bone tissue and enhance regenerative properties when mixed with xenograft material. We tested this hypothesis in vitro and in vivo using 3D-printed composite mPCL-HA scaffolds (wt 96%:4%) with the Voronoi design using an ISO 13485 certified additive manufacturing platform. The resulting scaffold porosity was 73% and minimal in vitro degradation (mass loss <1%) was observed over the period of 6 months. After loading the scaffolds with different types of fresh sheep xenograft and ectopic implantation in rats for 8 weeks, highly vascularized tissue without extensive fibrous encapsulation was found in all mPCL-HA Voronoi scaffolds and endochondral bone formation was observed, with no adverse host-tissue reactions. This study supports the use of mPCL-HA Voronoi scaffolds for further testing in future large preclinical animal studies prior to clinical trials to ultimately successfully advance the SGBR concept.</p

Scaffold Design Workflow - A Complete Demonstration

Demonstration video of the complete scaffold design workflow in the paper "The Development of a Modular Design Workflow for 3D Printable Bioresorbable Patient-Specific Bone Scaffolds to Facilitate Clinical Translation". Please download the video file for higher quality. Complete publication can be found at https://doi.org/10.1080/17452759.2023.2246434</p