Contact osteogenesis by biodegradable 3D-printed poly(lactide-co-trimethylene carbonate).

BACKGROUND: To support bone regeneration, 3D-printed templates function as temporary guides. The preferred materials are synthetic polymers, due to their ease of processing and biological inertness. Poly(lactide-co-trimethylene carbonate) (PLATMC) has good biological compatibility and currently used in soft tissue regeneration. The aim of this study was to evaluate the osteoconductivity of 3D-printed PLATMC templates for bone tissue engineering, in comparison with the widely used 3D-printed polycaprolactone (PCL) templates. METHODS: The printability and physical properties of 3D-printed templates were assessed, including wettability, tensile properties and the degradation profile. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were used to evaluate osteoconductivity and extracellular matrix secretion in vitro. In addition, 3D-printed templates were implanted in subcutaneous and calvarial bone defect models in rabbits. RESULTS: Compared to PCL, PLATMC exhibited greater wettability, strength, degradation, and promoted osteogenic differentiation of hBMSCs, with superior osteoconductivity. However, the higher ALP activity disclosed by PCL group at 7 and 21 days did not dictate better osteoconductivity. This was confirmed in vivo in the calvarial defect model, where PCL disclosed distant osteogenesis, while PLATMC disclosed greater areas of new bone and obvious contact osteogenesis on surface. CONCLUSIONS: This study shows for the first time the contact osteogenesis formed on a degradable synthetic co-polymer. 3D-printed PLATMC templates disclosed unique contact osteogenesis and significant higher amount of new bone regeneration, thus could be used to advantage in bone tissue engineering.

Local treatment of experimental mandibular osteomyelitis with an injectable biomimetic gentamicin hydrogel using a new rabbit model.

Mandibular osteomyelitis (OM) is a challenging disease. Our objective was to assess a new OM model in rabbits induced by arsenic trioxide and to assess the efficacy of local treatment of OM using injectable gentamicin-collagen hydrogels (GNT-COLL). OM was induced unilaterally by controlled confinement of arsenic trioxide paste to the root canal of lower incisors of rabbits, while OM progression was characterized for 16 weeks. On the other hand, two injectable COLL hydrogels functionalized with GNT were prepared and characterized for physicochemical properties; a simple GNT-COLL and a nanohydroxyapatite (nHA)- loaded hydrogel (GNT-COLL/nHA). The two hydrogels were evaluated to treat OM model, while a multidose intramuscular GNT solution served as positive control. Outcomes were assessed by standard methods at 4 and 12 weeks post-surgery. The clinical, radiographical, and histopathological findings provided evidence for the validity of the arsenic-induced OM. The results demonstrated that a single intra-lesional injection of the two hydrogels was more suppressive to OM compared to multidose systemic GNT. The composite GNT-COLL/nHA hydrogel proved to induce early preservation of alveolar bone (ridge) length and higher amount of bone area\total area at 4 weeks (40.53% ± 2.34) followed by GNT-COLL (32.21% ± 0.72). On the other hand, the positive control group revealed the least ridge length and bone area\total area (26.22% ± 1.32) at 4 weeks. Both hydrogels successfully arrested OM with no signs of recurrence for up to 12 weeks. Therefore, results support the greater advantages of the composite hydrogel as an osteogenic/antibiotic delivery system in OM treatment.

Corrigendum: Ectopic Bone Tissue Engineering in Mice Using Human Gingiva or Bone Marrow-Derived Stromal/Progenitor Cells in Scaffold-Hydrogel Constructs.

[This corrects the article DOI: 10.3389/fbioe.2021.783468.].

The bone regeneration capacity of 3D-printed templates in calvarial defect models: A systematic review and meta-analysis.

3D-printed templates are being used for bone tissue regeneration (BTR) as temporary guides. In the current review, we analyze the factors considered in producing potentially bioresorbable/degradable 3D-printed templates and their influence on BTR in calvarial bone defect (CBD) animal models. In addition, a meta-analysis was done to compare the achieved BTR for each type of template material (polymer, ceramic or composites). Database collection was completed by January 2018, and the inclusion criteria were all titles and keywords combining 3D printing and BTR in CBD models. Clinical trials and poorly-documented in vivo studies were excluded from this study. A total of 45 relevant studies were finally included and reviewed, and an additional check list was followed before inclusion in the meta-analysis, where material type, porosity %, and the regenerated bone area were collected and analyzed statistically. Overall, the capacity of the printed templates to support BTR was found to depend in large part on the amount of available space (porosity %) provided by the printed templates. Printed ceramic and composite templates showed the best BTR capacity, and the optimum printed template structure was found to have total porosity >50% with a pore diameter between 300 and 400 µm. Additional features and engineered macro-channels within the printed templates increased BTR capacity at long time points (12 weeks). Although the size of bone defects in rabbits was larger than in rats, BTR was greater in rabbits (almost double) at all time points and for all materials used. STATEMENT OF SIGNIFICANCE: In the present study, we reviewed the factors considered in producing degradable 3D-printed templates and their influence on bone tissue regeneration (BTR) in calvarial bone defects through the last 15 years. A meta-analysis was applied on the collected data to quantify and analyze BTR related to each type of template material. The concluded data states the importance of 3D-printed templates for BTR and indicates the ideal design required for an effective clinical translation. The evidence-based guidelines for the best BTR capacity endorse the use of printed composite and ceramic templates with total porosity >50%, pore diameter between 300 and 400 µm, and added engineered macro-channels within the printed templates.