Scaffold-guided bone regeneration is poised to revolutionize the management of critical-sized bone defects. However, translation into clinical practice has been hampered by the focus on bioresorbable scaffolds where the rate of degradation needs to match the rate of bone formation and metal plates are required to overcome their mechanical limitations. Metal plates are problematic because they cause stress shielding and X-ray perturbation, increasing the likelihood of hardware failure and interfering with post-operative radiotherapy and imaging. Segmental defects of the mandible are challenging due to high tensile and shear stresses encountered during mastication, with the ovine mandible especially vexing because of the high repetitive loads. Here we show long-term reconstruction of ovine segmental mandibulectomy defects using a permanent, patient-matched, numerically optimized, 3D-printed, thermally toughened, plasma-treated, and laser-sintered polyetherketone gyroid scaffold housing a resorbable ceramic lattice infused with a stem cell laden hydrogel serving as an osteoinductive reservoir of calcium. The durable clinical performance observed indicates a translatable alternative to traditional reconstruction using bone grafts with metal plate fixation.

Even with the best infection control protocols in place, the risk of a hospital-acquired infection of the surface of an implanted device remains significant. A bacterial biofilm can form and has the potential to escape the host immune system and develop resistance to conventional antibiotics, ultimately causing the implant to fail, seriously impacting patient well-being. Here, we demonstrate a 4 log reduction in the infection rate by the common pathogen S. aureus of 3D-printed polyaryl ether ketone (PAEK) polymeric surfaces by covalently binding the antimicrobial peptide Mel4 to the surface using plasma immersion ion implantation (PIII) treatment. The surfaces with added texture created by 3D-printed processes such as fused deposition-modelled polyether ether ketone (PEEK) and selective laser-sintered polyether ketone (PEK) can be equally well protected as conventionally manufactured materials. Unbound Mel4 in solution at relevant concentrations is non-cytotoxic to osteoblastic cell line Saos-2. Mel4 in combination with PIII aids Saos-2 cells to attach to the surface, increasing the adhesion by 88% compared to untreated materials without Mel4. A reduction in mineralisation on the Mel4-containing surfaces relative to surfaces without peptide was found, attributed to the acellular portion of mineral deposition.

Autologous bone replacement remains the preferred treatment for segmental defects of the mandible; however, it cannot replicate complex facial geometry and causes donor site morbidity. Bone tissue engineering has the potential to overcome these limitations. Various commercially available calcium phosphate-based bone substitutes (Novabone^®, BioOss^®, and Zengro^®) are commonly used in dentistry for small bone defects around teeth and implants. However, their role in ectopic bone formation, which can later be applied as vascularized graft in a bone defect, is yet to be explored. Here, we compare the above-mentioned bone substitutes with autologous bone with the aim of selecting one for future studies of segmental mandibular repair. Six female sheep, aged 7–8 years, were implanted with 40 mm long four-chambered polyether ether ketone (PEEK) bioreactors prepared using additive manufacturing followed by plasma immersion ion implantation (PIII) to improve hydrophilicity and bioactivity. Each bioreactor was wrapped with vascularized scapular periosteum and the chambers were filled with autologous bone graft, Novabone^®, BioOss^®, and Zengro^®, respectively. The bioreactors were implanted within a subscapular muscle pocket for either 8 weeks (two sheep), 10 weeks (two sheep), or 12 weeks (two sheep), after which they were removed and assessed by microCT and routine histology. Moderate bone formation was observed in autologous bone grafts, while low bone formation was observed in the BioOss^® and Zengro^® chambers. No bone formation was observed in the Novabone^® chambers. Although the BioOss^® and Zengro^® chambers contained relatively small amounts of bone, endochondral ossification and retained hydroxyapatite suggest their potential in new bone formation in an ectopic site if a consistent supply of progenitor cells and/or growth factors can be ensured over a longer duration.

Considerable research is being undertaken to develop novel biomaterials-based approaches for surgical reconstruction of bone defects. This extends to three-dimensional (3D) printed materials that provide stable, structural, and functional support in vivo . However, few preclinical models can simulate in vivo human biological conditions for clinically relevant testing. In this study we describe a novel ovine model that allows evaluation of in vivo osteogenesis via contact with bone and/or periosteum interfaced with printed polymer bioreactors loaded with biomaterial bone substitutes. The infraspinous scapular region of 14 Dorset cross sheep was exposed. Vascularized periosteum was elevated either attached to the infraspinatus muscle or separately. In both cases, the periosteum was supplied by the periosteal branch of the circumflex scapular vessels. In eight sheep, a 3D printed 4-chambered polyetheretherketone bioreactor was wrapped circumferentially in vascularized periosteum. In 6 sheep, 12 double-sided 3D printed 2-chambered polyetherketone bioreactors were secured to the underlying bone allowing direct contact with the bone on one side and periosteum on the other. Our model enabled simultaneous testing of up to 24 (12 double-sided) 10 × 10 × 5 mm bioreactors per scapula in the flat contact approach or a single 40 × 10 mm four-chambered bioreactor per scapula using the periosteal wrap. De novo bone growth was evaluated using histological and radiological analysis. Of importance, the experimental model was well tolerated by the animals and provides a versatile approach for comparing the osteogenic potential of cambium on the bone surface and elevated with periosteum. Furthermore, the periosteal flaps were sufficiently large for encasing bioreactors containing biomaterial bone substitutes for applications such as segmental mandibular reconstruction.

The additive manufacturing technology known as selective‐laser‐sintering is available for the poly‐aryl‐ether‐ketone (PAEK) family of high‐strength polymers, enabling the rapid production of personalized dental and mandibular reconstructions at or near the point‐of‐care. PAEK mandibular segmental replacements, bridges, and abutments are transitioning to clinical use. There remains a need for improved adhesion between PAEK polymers and dental adhesives including dental composite resin cements. Without surface modification, there is a weak bond to PAEK polymers, especially when the surface of the polymer is smooth. Plasma‐immersion‐ion‐implantation (PIII) is applied to demonstrate a significant increase in the bond strength between Polyether–ether–ketone (PEEK) and Poly–ether–ketone (PEK) polymers and a commonly used dental composite resin cement, for multiple levels of interface roughness. A validated predictive model for the bond strength as a function of surface roughness expressed as a surface area ratio is presented that demonstrates the relative effect of PIII and mechanical interlocking. The results show that the bond strength achieved using PIII is retained even when the primer step is omitted, an important advance as the primer has been associated with hydrolysis‐induced weakening. A long‐term water immersion test shows that the PIII‐assisted primer‐free bond retains its strength while all primer‐assisted bonds are weakened.