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The aim of the present preclinical in vivo study was to evaluate whether a modified “drill-only” protocol, involving slight underpreparation of the implant site, may have an effect on aspects of osseointegration of a novel bone-level tapered implant, compared with the “standard drilling” protocol involving taping and profiling of the marginal aspect of the implant socket. In each side of the edentulated and completely healed mandible of 11 minipigs, 2 tapered implants (8 mm long × 4.1 mm Ø, BLT; Institut Straumann AG, Basel, Switzerland) were installed either with the drill-only or the standard drilling protocol. Significantly lower average insertion torque values were recorded for the standard drilling protocol group (52 ± 29 Ncm) compared with the drill-only group (70 ± 27 Ncm) (t test, P ≤ 0.05); no significant difference was observed between the 2 groups regarding implant stability, by means of resonance frequency analysis (75 ± 8 vs. 75 ± 6, respectively). Half of the implants were immediately loaded and the rest were submerged, providing observation times of 8 or 4 wk, respectively. Non-decalcified histological and histomorphometric analysis of the implants with surrounding tissues showed no significant differences between the 2 drilling protocols regarding the distance from the implant platform to the first coronal bone-to-implant contact (f-BIC), the total bone-to-implant contact (BIC) as a percentage of the total implant perimeter, and the bone density in an area extending 1 mm laterally from the implant (BATA) within 2 rectangular regions of interest (ROIs) 4 mm in height, representing the coronal (parallel-walled) and apical (tapered) aspect of the implant (ROI 1 and ROI 2, respectively) in non-submerged implants. In general, marginal peri-implant bone levels were at or slightly apical to the implant platform, and large amounts of bone-to-implant contact were observed. In contrast, immediately loaded implants placed with the drill-only protocol showed statistically significantly lower BIC values (66% ± 13.7%) compared with those installed with the standard drilling protocol (74.8% ± 11.2%) (P = 0.018). In addition, although marginal bone levels were in most of the immediately loaded implants at or slightly apical to the implant platform, some of the implants installed with the drill-only protocol showed marginal bone loss and crater formation. Thus, in this model system, even slight underpreparation of the implant socket appeared to compromise osseointegration of immediately loaded bone-level tapered implants. [ABSTRACT FROM AUTHOR]

Primary mechanical stability, as measured by maximum insertion torque and resonance frequency analysis, is generally considered to be positively associated with successful secondary stability and implant success. Primary implant stability can be affected by several factors, including the quality and quantity of available bone, the implant design, and the surgical procedure. The use of a tapered implant design, for instance, has been shown to result in good primary stability even in clinical scenarios where primary stability is otherwise difficult to achieve with traditional cylindrical implants—for example, in soft bone and for immediate placement in extraction sockets. In this study, bone-type specific drill procedures are presented for a novel Straumann bone level tapered implant that ensure maximum insertion torque values are kept within the range of 15 to 80 Ncm. The drill procedures are tested in vitro using polyurethane foam blocks of variable density, ex vivo on explanted porcine ribs (bone type 3), and finally in vivo on porcine mandibles (bone type 1). In each test site, adapted drill procedures are found to achieve a good primary stability. These results are further translated into a finite element analysis model capable of predicting primary stability of tapered implants. In conclusion, we have assessed the biomechanical behavior of a novel taper-walled implant in combination with a bone-type specific drill procedure in both synthetic and natural bone of various types, and we have developed an in silico model for predicting primary stability upon implantation. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present study was to compare a novel tapered, double-threaded self-tapping tissue-Level design implant (TLC) to a well-established parallel walled tissue-level (TL) implant in terms of primary and secondary stability over time., Materials and Methods: Test TLC (n = 10/per timepoint) and control TL (n = 10/per timepoint) implants were placed in the mandible of minipigs and left for submerged healing for 3, 6, and 12 weeks. Maximum insertion torque and implant stability quotient (ISQ) were measured for each implant at placement. Osseointegration and cortical bone maintenance were histologically evaluated by measuring total bone-to-implant contact (BIC) and first bone-to-implant contact (fBIC)., Results: A significantly higher maximum insertion torque was measured for the test implant TLC compared to the control TL implant (57.83 ± 24.73 Ncm and 22.62 ± 23.16 Ncm, respectively; p < .001). The mean ISQ values were comparable between the two implant types (75.00 ± 6.70 for TL compared to 75.40 ± 3.20 for TLC, p = .988). BIC was comparable between both implant types at each of the evaluated time points. The fBIC was found to be significantly more coronal at 12 weeks for the TLC implant compared to the TL implant (0.31 ± 0.83 mm for TLC compared to -0.22 ± 0.85 for TL, p = .027)., Conclusion: The novel tapered tissue level design implant showed improved primary stability and an overall improved crestal bone height maintenance compared to the parallel walled design at 12 weeks., (© 2024 The Author(s). Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Surface design plays a critical role in determining the integration of dental implants with bone tissue. Femtosecond laser-texturing has emerged as a breakthrough technology offering excellent uniformity and reproducibility in implant surface features. However, when compared to state-of-the-art sandblasted and acid-etched surfaces, laser-textured surface designs typically underperform in terms of osseointegration. This study investigates the capacity of a bio-inspired femtosecond laser-textured surface design to enhance osseointegration compared to state-of-the-art sandblasted & acid-etched surfaces. Laser-texturing facilitates the production of an organized trabeculae-like microarchitecture with superimposed nano-scale laser-induced periodic surface structures on both 2D and 3D samples of titanium-zirconium-alloy. Following a boiling treatment to modify the surface chemistry, improving wettability to a contact angle of 10°, laser-textured surfaces enhance fibrin network formation when in contact with human whole blood, comparable to state-of-the-art surfaces. In vitro experiments demonstrate that laser-textured surfaces significantly outperform state-of-the-art surfaces with a 2.5-fold higher level of mineralization by bone progenitor cells after 28 days of culture. Furthermore, in vivo evaluations reveal superior biomechanical integration of laser-textured surfaces after 28 days of implantation. Notably, during abiological pull-out tests, laser-textured surfaces exhibit comparable performance, suggesting that the observed enhanced osseointegration is primarily driven by the biological response to the surface., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Aims: To test whether titanium surface roughness disparity might be used to specifically guide the behavior of gingiva fibroblasts and keratinocytes, thereby improving the quality of soft tissue (ST) integration around abutments., Methods: Titanium discs resembling the roughness of enamel (M) or cementum (MA) were created with normal or increased hydrophilicity and used as substrates for human fibroblasts and keratinocytes. Adhesion and proliferation assays were performed to assess cell-type specific responses upon encountering the different surfaces. Additionally, immunofluorescence and qPCR analyses were performed to study more in depth the behavior of fibroblasts and keratinocytes on MA and M surfaces, respectively., Results: While enamel-like M surfaces supported adhesion, growth and a normal differentiation potential of keratinocytes, cementum-emulating MA surfaces specifically impaired the growth of keratinocytes. Vice versa, MA surfaces sustained regular adhesion and proliferation of fibroblasts. Yet, a more intimate adhesion between fibroblasts and titanium was achieved by an increased hydrophilicity of MA surfaces, which was associated with an increased expression of elastin., Conclusion: The optimal titanium implant abutment might be achieved by a bimodal roughness design, mimicking the roughness of enamel (M) and cementum with increased hydrophilicity (hMA), respectively. These surfaces can selectively elicit cell responses favoring proper ST barrier by impairing epithelial downgrowth and promoting firm adhesion of fibroblasts., (© 2024 The Author(s). Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Objectives: To investigate the impact of a Ti-Sr-O technology, applied to either a turned surface or an SLA surface, on the mechanical robustness of osseointegration, benchmarked against the SLActive surface., Material and Methods: Ti discs (6.25-mm-diameter and 2-mm-thick) with three different surfaces were inserted on the proximal-anterior part of the tibial plateau of adult Swedish loop rabbits: (I) turned surface modified with Ti-Sr-O (turned + Ti-Sr-O), (II) SLA surface modified with Ti-Sr-O (SLA + Ti-Sr-O), and (III) SLActive surface (SLActive). Following a healing period of 2 weeks and 4 weeks, the pull-out (PO) force needed to detach the discs from the bone was assessed, as a surrogate of osseointegration., Results: The SLActive surface exhibited statistically significant higher median PO forces, compared with the SLA + Ti-Sr-O surfaces at both 2- and 4 weeks post-op (p > .05). In this study, no single turned + Ti-Sr-O surface disk was integrated., Conclusions: The tested Ti-Sr-O technology failed to enhance osseointegration; however, this finding may be related to the inappropriateness of the rabbit tibia plateau model for assessing third-generation implant surface technologies, due to the limited diffusion and clearance at the disk-bone interface., (© 2023 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Objectives: To develop a new preclinical model to study early implant loss, where local infection conditions would impair the implant osseointegration., Materials and Methods: Forty-eight smooth, 2.9-mm diameter experimental implants were placed in the mandible of 8 beagle dogs (3 in each side). In half of the animals (test group, n = 24 implants), the implants received ligatures around the implant-abutment connection. In the other half, no ligatures were placed (control group, n = 24 implants). Four weeks later, implants were extracted in a flapless approach and standard 3.3-mm diameter SLActive implants were placed into the same osteotomy site without any further drilling. Eight weeks after the second implantation, animals were sacrificed and analyzed in terms of implant survival., Results: After 8 weeks of healing, 4 implants were lost in the control group and 14 in the test group. This corresponded to a 17.4% of early implant loss in the control group and 58.3% in the test. Most of the early failures occurred within the first 5 weeks of healing., Conclusions: Implants placed in a pre-contaminated site present higher early loss than those placed in a non-contaminated site. This study represents a valid and robust preclinical model to study mechanisms and reduction of early implant loss as new technologies become available., Clinical Relevance: Scientific rationale for the study: There is lack of animal models to study early implant loss. Thus, a proposal of a new model is presented. With the validation of this model, new technologies can be implemented to prevent early implant loss., (© 2022. The Author(s).)

Background: The goal of this study was to evaluate hard tissue response following guided bone regeneration using commercially available bovine bone grafts and collagen membranes; bilayer collagen membrane and porcine pericardium-based membrane, by means of a non-destructive three-dimensional (3D) computerized volumetric analysis following microtomography reconstruction., Material and Methods: Bone regenerative properties of various bovine bone graft materials were evaluated in the Göttingen minipig model. Two standardized intraosseous defects (15mm x 8mm x 8mm) were created bilaterally of the mandible of eighteen animals (n=72 defects). Groups were nested within the same subject and randomly distributed among the sites: (i) negative control (no graft and membrane), (ii) bovine bone graft/bilayer collagen membrane (BOB) (iii) Bio-Oss® bone graft/porcine pericardium-based membrane (BOJ) and (iv) cerabone® bone graft/porcine pericardium-based membrane (CJ). Samples were harvested at 4, 8, and 12-week time points (n=6 animal/time point). Segments were scanned using computerized microtomography (μCT) and three dimensionally reconstructed utilizing volumetric reconstruction software. Statistical analyses were performed using IBM SPSS with a significance level of 5%., Results: From a temporal perspective, tridimensional evaluation revealed gradual bone ingrowth with the presence of particulate bone grafts bridging the defect walls, and mandibular architecture preservation over time. Volumetric analysis demonstrated no significant difference between all groups at 4 weeks (p>0.127). At 8 and 12 weeks there was a higher percentage of new bone formation for control and CJ groups when compared to BOB and BOJ groups (p<0.039). The natural bovine bone graft group showed more potential for graft resorption over time relative to bovine bone graft, significantly different between 4 and 8 weeks (p<0.003)., Conclusions: Volumetric analysis yielded a favorable mandible shape with respect to time through the beneficial balance between graft resorption/bone regenerative capacity for the natural bovine bone graft.

Purpose: To determine the impact of experimentally preformed peri-implant crater-shaped bone defects on the evolution of in situ microbiota and development of bone defects compared to those induced over time by ligature placement only., Methods: Implants were installed in the mandibles of eight dogs. Standardized bone defects were preformed in four test animals but not in the other four control animals, prior to implant (3.3 mm × 8 mm) installation. After 2 months of healing, peri-implantitis was induced with silk ligatures in both groups for 2 months. Microbial samples were obtained from implants and teeth for analysis at three time points (qPCR), and the average depths of the bone defects were measured., Results: At the baseline, the total marker load of periodontal-pathogenic bacteria (TML) for teeth accounted for 5.2% (0-17.4%). After implant healing, TMLs for implants and teeth were comparable (7.1% [0.3-17.4%]). The TML of both groups was 3.5%, 2 months after ligature placement. Bone defects had a mean depth of 1.84 mm at preformed defects and 1.64 mm at control sites (P > 0.05)., Conclusion: Preformed defects in the test group showed comparable results to the control group in terms of TML, the incidence of periodontal-pathogenic bacteria, and bone defect depth.

Xenograft bone substitutes are commonly used to increase bone volume and height in the deficient posterior maxilla. The addition of enamel matrix derivate (Emdogain) could increase the efficiency of the bone healing process. The aim of this prospective randomized, controlled split-mouth design study was to compare the percentage of newly formed bone in sinus floor augmentation with deproteinized bovine bone mineral with or without the addition of enamel matrix derivative after 6 months of healing. Sixteen bilateral sinus floor augmentation procedures were performed. Deproteinized bovine bone mineral combined with enamel matrix derivative (test) and deproteinized bovine bone mineral alone (control) groups were randomly allocated within each patient. Six months after augmentation and concurrent to implant placement, bone biopsies were taken for histomorphometric analysis. Additionally, implant survival and peri-implant bone levels were radiographically assessed at baseline and 24 months after functional loading. Histomorphometric analysis revealed a significantly higher amount of newly formed bone in the test group compared with the control group (22.6% and 15.5%, respectively; P = .033). No significant differences in the amount of remaining graft or connective tissue was found. Enamel matrix derivative added to deproteinized bovine bone mineral particles significantly increased new bone formation in sinus lift procedures in edentulous or partially edentulous patients with deficient bilateral posterior alveolar ridges requiring augmentation for implant placement.

Objectives: The impact of the implant surface material and roughness on inflammatory processes in peri-implantitis is not entirely clear. Hence, we investigated how titanium and zirconia surfaces with different roughness influence the susceptibility of primary human gingival fibroblasts to different inflammatory stimuli., Methods: Primary human gingival fibroblasts were isolated from 8 healthy individuals and cultured on following surfaces: smooth titanium machined surface (TiM), smooth zirconia machined surface (ZrM), moderately rough titanium surface (SLA), or moderately rough zirconia surface (ZLA). Subsequently, stimulation with one of the following stimuli was performed: Porphyromonas gingivalis lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, interleukin (IL)-1β. The resulting production of IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1 was measured by qPCR and ELISA., Results: P. gingivalis LPS induced IL-6 and MCP-1 production was slightly higher on titanium surfaces compared to zirconia surfaces. IL-1β induced IL-6 production was not affected by any surface characteristic. The production of MCP-1 in response to IL-1β was higher on smooth compared to rough surfaces and was not affected by the material. The production of IL-6 and MCP-1 in response to TNF-α was most strongly affected by surface characteristics. Higher production of these cytokine was observed on smooth compared to rough surfaces and on titanium compared to zirconia surfaces. Surface characteristics had only minor effects on IL-8 production., Significance: The susceptibility of primary gingival fibroblasts to inflammation depends on various factors, such as surface material, surface roughness and the nature of inflammatory stimuli. All these factors might determine susceptibility to peri-implantitis., (Copyright © 2020 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Purpose: Only limited information on the effect of implant surface hydrophilicity in conjunction with simultaneous bone augmentation is available. In this study, new bone growth around implants with a superhydrophilic modSLA (SLActive) and hydrophobic SLA (SLA) surface were compared in circumferential defects when grafted in conjunction with mineralized cancellous bone allograft (MCBA, maxgraft) or sintered bovine bone mineral (SBBM, cerabone)., Materials and Methods: The osseointegration and bone formation in circumferential defects in minipig mandibles around Straumann Roxolid, Ø 3.3 mm, length 8 mm; either SLA or SLActive, were evaluated. Following implant placement, the 2-mm circumferential defects around the implants were filled with MCBA or SBBM. Distance from implant shoulder to first bone-to-implant contact (f-BIC), percentage of bone-to-implant contact (BIC), and bone aggregate percentage (amount of new bone and remaining graft) within the defect area were evaluated after 8 weeks of healing., Results: In the SBBM group, lingual fBIC and buccal BIC were significantly lower for SLA (mean -0.404 ± 0.579 mm for modSLA versus -1.191 ± 0.814 mm for SLA, P = .021 and mean 62.61% ± 9.49% for modSLA versus 34.67% ± 24.41% for SLA, P = .047, respectively). Bone aggregate percentage was significantly higher for modSLA versus SLA implants in SBBM (77.84% ± 6.93% versus 64.49% ± 13.12%; P = .045). The differences between implant surfaces in MCBA showed a similar trend but were less pronounced than in the SBBM group and did not reach a statistically significant level., Conclusion: The results suggest that implants with a superhydrophilic modSLA surface are more conducive to faster osseointegration even in conjunction with simultaneous bone grafting procedures.

Purpose: The increasing prevalence of obesity or metabolic syndrome (O/MS) and type 2 diabetes mellitus (DM) remains a global health concern. Clinically relevant and practical translational models mimicking human characteristics of these conditions are lacking. This study aimed to demonstrate proof of concept of the induction of stable O/MS and type 2 DM in a Göttingen minipig model and validate both of these disease-adjusted Göttingen minipig models as impaired healing models for the testing of dental implants., Materials and Methods: Nine minipigs were split into 3 groups-control (normal diet), obese (cafeteria diet), and diabetic (cafeteria diet plus low-dosage streptozotocin)-followed by placement of dental implants. Inflammatory markers including tumor necrosis factor α, C-reactive protein, and cortisol were recorded for each study group. Removal torque was measured, and histomorphometric analysis (bone-to-implant contact and bone area fraction occupancy) was performed., Results: O/MS pigs showed, on average, a 2-fold increase in plasma C-reactive protein (P < .05) and cortisol (P < .09) concentrations compared with controls; DM pigs showed, on average approximately, a 40-fold increase in plasma tumor necrosis factor α levels (P < .05) and a 2-fold increase in cortisol concentrations (P < .05) compared with controls. The impact of O/MS and DM on implants was determined. The torque to interface failure was highest in the control group (200 N-cm) and significantly lower in the O/MS (90 N-cm) and DM (60 N-cm) groups (P < .01). Bone formation around implants was significantly greater in the control group than in the O/MS and DM groups (P < .02)., Conclusions: Both O/MS and DM minipigs express a human-like disease phenotype, and both presented bone-healing impairment around dental implants. Our finding of no significant difference between type 2 DM and O/MS in bone formation around implants provides evidence that further investigation of the impact of O/MS is warranted., (Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Dimensional changes of the alveolar bone following tooth extraction are a major challenge in daily dental practice. To limit bone loss, a variety of biomaterials including bone grafts, barrier membranes, and growth factors have been utilized either alone or in combination therapies to increase the speed and quality of new bone formation. The aim of the present in vitro study was to investigate the regenerative potential of Osteogain®, a new liquid carrier system of enamel matrix derivative (EMD) in combination with an absorbable collagen sponge (ACS) specifically designed for extraction socket healing., Materials and Methods: The potential of ACS was first investigated using ELISA to quantify total amelogenin adsorption and release from 0 to 10 days. Thereafter, the cellular effects of ST2 pre-osteoblasts were investigated for cellular attachment at 8 h and cell proliferation at 1, 3, and 5 days as well as osteoblast differentiation by real-time PCR and alizarin red staining for cells seeded on (1) tissue culture plastic, (2) ACS alone, and (3) ACS + Osteogain®., Results: ACS efficiently loaded nearly 100% of the amelogenin proteins found in Osteogain® which were gradually released up to a 10-day period. Osteogain® also significantly induced a 1.5-fold increase in cell attachment and resulted in a 2-6-fold increase in mRNA levels of osteoblast differentiation markers including runt-related transcription factor 2 (Runx2), collagen1a2, alkaline phosphatase, and bone sialoprotein as well as induced alizarin red staining when combined with ACS., Conclusions: In summary, these findings suggest that Osteogain® is capable of inducing osteoblast attachment and differentiation when combined with ACS. Future animal studies and randomized human clinical trials are necessary to further support these findings., Clinical Relevance: The use of Osteogain® in combination with ACS may provide a valuable means to limit dimensional changes following tooth extraction.

Purpose: Tapered implants are thought to result in equivalent long-term stability and marginal peri-implant bone height in comparison to cylindrical implants. The goal of this study was to compare the primary stability and osseointegration of a novel bone-level tapered-wall implant to a control bone-level cylindrical implant with exactly the same surface characteristics, in a direct side-by-side comparison in an animal model., Materials and Methods: Mandibular premolars and first molars were extracted in 11 G.ttingen minipigs, and healing was allowed for 3 months. Six implants were placed with a 4-week surgical lag time between hemimandibles (three per side), and either immediately loaded (first implantation time point) or submerged (second implantation time point). Eight-mm-long × 4.1-mm-diameter titanium screw-type bone-level implants with tapered (two per side) and cylindrical bodies (one per side) were used (Institut Straumann); insertion torque and implant stability were measured, and the soft tissue was closed. Standardized radiographs were taken at implant placement and at sacrifice. Following a healing period of 1 month from the last surgical intervention (8 weeks total healing time for loaded implants; 4 weeks total healing time for nonloaded implants), the animals were sacrificed and mandibular blocks were harvested for nondecalcified histologic and histomorphometric analysis., Results: All implants were integrated radiographically and osseointegrated histologically. Maximum insertion torque measurements and implant stability quotient values showed no significant difference between tapered and cylindrical implants. Histomorphometric analysis also resulted in comparable bone-to-implant contact values between the implant types and similarly limited marginal peri-implant bone resorption; no significant differences were observed regarding all the evaluated parameters between the groups, regardless of the loading regime., Conclusion: In a direct side-by-side comparison, in an intraoral minipig model, a novel bone-level tapered screw implant with an SLActive surface showed comparable clinical and histologic outcomes to a parallel-walled bone-level screw implant with an SLActive surface.

Purpose: The cellular component of subchondral bone is thought to be responsible for aberrant bone remodeling in osteoarthritis (OA). Direct phenotypical analysis of the cellular compartment is critical to better understand the OA disease process. This study provides proof-of-principle for flow cytometry-based phenotyping of isolated subchondral trabecular bone (STB) marrow cells without prior use of cell culture techniques., Methods: Tibial plateaus were obtained from OA patients undergoing total knee arthroplasty. Subchondral bone chips were digested with collagenase IA and single cell suspensions were directly phenotyped using flow cytometry. Cells were analyzed for the expression of alkaline phosphatase (ALP) as osteoblast/osteoprogenitor marker and monocyte/macrophage markers (CD14, CD68, HLA-DR, CD115)., Results: MTT staining revealed abundant viable cells in the bone marrow compartment of STB prior to digestion, which were efficiently released by collagenase. Within the CD45-negative cell fraction, approximately 20% of the cells were positive for the early osteoblast/osteoprogenitor marker ALP. Within the CD45+ hematopoietic cell fraction, the majority of cells were of monocytic origin (>80%) displaying strong surface expression of CD14. Discreet macrophage populations (CD14+/HLA-DR+/CD68+) and putative osteoclast progenitors (CD45+/HLA-DR-/CD115+) were unequivocally identified. Osteoblast, macrophage and osteoclast progenitor presence in the subchondral bone unit (SBU) was confirmed by (immuno)histochemical staining for osteocalcin, CD68 and tartrate-resistant acid phosphatase, respectively., Conclusions: Flow cytometric analysis is a valuable methodology to study the cellular compartment of STB marrow. This method provides a proof of principle that the whole resident cell population can be directly phenotypically characterized without the prior use of cell culture techniques., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

In embryonic models and stem cell systems, mesenchymal cells derived from the neuroectoderm can be distinguished from mesoderm-derived cells by their Hox-negative profile--a phenotype associated with enhanced capacity of tissue regeneration. We investigated whether developmental origin and Hox negativity correlated with self-renewal and environmental plasticity also in differentiated cells from adults. Using hyaline cartilage as a model, we showed that adult human neuroectoderm-derived nasal chondrocytes (NCs) can be constitutively distinguished from mesoderm-derived articular chondrocytes (ACs) by lack of expression of specific HOX genes, including HOXC4 and HOXD8. In contrast to ACs, serially cloned NCs could be continuously reverted from differentiated to dedifferentiated states, conserving the ability to form cartilage tissue in vitro and in vivo. NCs could also be reprogrammed to stably express Hox genes typical of ACs upon implantation into goat articular cartilage defects, directly contributing to cartilage repair. Our findings identify previously unrecognized regenerative properties of HOX-negative differentiated neuroectoderm cells in adults, implying a role for NCs in the unmet clinical challenge of articular cartilage repair. An ongoing phase 1 clinical trial preliminarily indicated the safety and feasibility of autologous NC-based engineered tissues for the treatment of traumatic articular cartilage lesions., (Copyright © 2014, American Association for the Advancement of Science.)

Developing tools to reproduce and manipulate the cell micro-environment, including the location and shape of cell patterns, is essential for tissue engineering. Parallel to inkjet printing and pressure-operated mechanical extruders, laser-assisted bioprinting (LAB) has emerged as an alternative technology to fabricate two- and three-dimensional tissue engineering products. The objective of this work was to determine laser printing parameters for patterning and assembling nano-hydroxyapatite (nHA) and human osteoprogenitors (HOPs) in two and three dimensions with LAB. The LAB workstation used in this study comprised an infrared laser focused on a quartz ribbon that was coated with a thin absorbing layer of titanium and a layer of bioink. The scanning system, quartz ribbon and substrate were piloted by dedicated software, allowing the sequential printing of different biological materials into two and/or three dimensions. nHA printing material (bioink) was synthesized by chemical precipitation and was characterized prior and following printing using transmission electron microscopy, Fourier transformed infrared spectroscopy and x-ray diffraction. HOP bioink was prepared using a 30 million cells ml(-1) suspension in culture medium and cells were characterized after printing using a Live/Dead assay and osteoblastic phenotype markers (alcaline phosphatase and osteocalcin). The results revealed that LAB allows printing and organizing nHA and HOPs in two and three dimensions. LAB did not alter the physico-chemical properties of nHA, nor the viability, proliferation and phenotype of HOPs over time (up to 15 days). This study has demonstrated that LAB is a relevant method for patterning nHA and osteoblastic cells in 2D, and is also adapted to the bio-fabrication of 3D composite materials.

Over this decade, cell printing strategy has emerged as one of the promising approaches to organize cells in two and three dimensional engineered tissues. High resolution and high speed organization of cells are some of the key requirements for the successful fabrication of cell-containing two or three dimensional constructs. So far, none of the available cell printing technologies has shown an ability to concomitantly print cells at a cell-level resolution and at a kHz range speed. We have studied the effect of the viscosity of the bioink, laser energy, and laser printing speed on the resolution of cell printing. Accordingly, we demonstrate that a laser assisted cell printer can deposit cells with a microscale resolution, at a speed of 5 kHz and with computer assisted geometric control. We have successfully implemented such a cell printing precision to print miniaturized tissue like layouts with de novo high cell density and micro scale organization.