The COMBO window: A chronic cranial implant for multiscale circuit interrogation in mice.

Neuroscientists studying the neural correlates of mouse behavior often lack access to the brain-wide activity patterns elicited during a specific task of interest. Fortunately, large-scale imaging is becoming increasingly accessible thanks to modalities such as Ca2+ imaging and functional ultrasound (fUS). However, these and other techniques often involve challenging cranial window procedures and are difficult to combine with other neuroscience tools. We address this need with an open-source 3D-printable cranial implant-the COMBO (ChrOnic Multimodal imaging and Behavioral Observation) window. The COMBO window enables chronic imaging of large portions of the brain in head-fixed mice while preserving orofacial movements. We validate the COMBO window stability using both brain-wide fUS and multisite two-photon imaging. Moreover, we demonstrate how the COMBO window facilitates the combination of optogenetics, fUS, and electrophysiology in the same animals to study the effects of circuit perturbations at both the brain-wide and single-neuron level. Overall, the COMBO window provides a versatile solution for performing multimodal brain recordings in head-fixed mice.

Occipital-synarcual joint mobility in ratfishes (Chimaeridae) and its possible adaptive role.

The neurocranial elevation generated by axial muscles is widespread among aquatic gnathostomes. The mechanism has two functions: first, it contributes to the orientation of the mouth gape, and second, it is involved in suction feeding. To provide such mobility, anatomical specialization of the anterior part of the vertebral column has evolved in many fish species. In modern chimaeras, the anterior part of the vertebral column develops into the synarcual. Possible biological roles of the occipital-synarcual joint have not been discussed before. Dissections of the head of two species of ratfishes (Chimaera monstrosa and Chimaera phantasma) confirmed the heterocoely of the articulation surface between the synarcual and the neurocranium, indicating the possibility of movements in the sagittal and frontal planes. Muscles capable of controlling the movements of the neurocranium were described. The m. epaxialis is capable of elevating the head, the m. coracomandibularis is capable of lowering it if the mandible is anchored by the adductor. Lateral flexion is performed by the m. lateroventralis, for which this function was proposed for the first time. The first description of the m. epaxialis profundus is given, its function is to be elucidated in the future. Manipulations with joint preparations revealed a pronounced amplitude of movement in the sagittal and frontal planes. Since chimaeras generate weak decrease in pressure in the oropharyngeal cavity when sucking in prey, we hypothesised the primary effect of neurocranial elevation, in addition to the evident lateral head mobility, is accurate prey targeting.

Using your head - cranial steering in pterosaurs.

The vast majority of pterosaurs are characterized by relatively large, elongate heads that are often adorned with large, elaborate crests. Projecting out in front of the body, these large heads and any crests must have had an aerodynamic effect. The working hypothesis of the present study is that these oversized heads were used to control the left-right motions of the body during flight. Using digital models of eight non-pterodactyloids ("rhamphorhyncoids") and ten pterodactyloids, the turning moments associated with the head + neck show a close and consistent correspondence with the rotational inertia of the whole body about a vertical axis in both groups, supporting the idea of a functional relationship. Turning moments come from calculating the lateral area of the head (plus any crests) and determining the associated lift (aerodynamic force) as a function of flight speed, with flight speeds being based on body mass. Rotational inertias were calculated from the three-dimensional mass distribution of the axial body, the limbs, and the flight membranes. The close correlation between turning moment and rotational inertia was used to revise the life restorations of two pterosaurs and to infer relatively lower flight speeds in another two.

Spatiotemporal Distributions of Acoustic Propagation in Skull During Ultrasound Neuromodulation.

There is widespread interest and concern about the evidence and hypothesis that the auditory system is involved in ultrasound neuromodulation. We have addressed this problem by performing acoustic shear wave simulations in mouse skull and behavioral experiments in deaf mice. The simulation results showed that shear waves propagating along the skull did not reach sufficient acoustic pressure in the auditory cortex to modulate neurons. Behavioral experiments were subsequently performed to awaken anesthetized mice with ultrasound targeting the motor cortex or ventral tegmental area (VTA). The experimental results showed that ultrasound stimulation (US) of the target areas significantly increased arousal scores even in deaf mice, whereas the loss of ultrasound gel abolished the effect. Immunofluorescence staining also showed that ultrasound can modulate neurons in the target area, whereas neurons in the auditory cortex required the involvement of the normal auditory system for activation. In summary, the shear waves propagating along the skull cannot reach the auditory cortex and induce neuronal activation. Ultrasound neuromodulation-induced arousal behavior needs direct action on functionally relevant stimulation targets in the absence of auditory system participation.

tFUSFormer: Physics-Guided Super-Resolution Transformer for Simulation of Transcranial Focused Ultrasound Propagation in Brain Stimulation.

Transcranial focused ultrasound (tFUS) has emerged as a new mode of non-invasive brain stimulation (NIBS), with its exquisite spatial precision and capacity to reach the deep regions of the brain. The placement of the acoustic focus onto the desired part of the brain is critical for successful tFUS procedures; however, acoustic wave propagation is severely affected by the skull, distorting the focal location/shape and the pressure level. High-resolution (HR) numerical simulation allows for monitoring of acoustic pressure within the skull but with a considerable computational burden. To address this challenge, we employed a 4× super-resolution (SR) Swin Transformer method to improve the precision of estimating tFUS acoustic pressure field, targeting operator-defined brain areas. The training datasets were obtained through numerical simulations at both ultra-low (2.0 [Formula: see text]) and high (0.5 [Formula: see text]) resolutions, conducted on in vivo CT images of 12 human skulls. Our multivariable datasets, which incorporate physical properties of the acoustic pressure field, wave velocity, and skull CT images, were utilized to train three-dimensional SR models. We found that our method yielded 87.99 ± 4.28% accuracy in terms of focal volume conformity under foreseen skull data, and accuracy of 82.32 ± 5.83% for unforeseen skulls, respectively. Moreover, a significant improvement of 99.4% in computational efficiency compared to the traditional 0.5 [Formula: see text] HR numerical simulation was shown. The presented technique, when adopted in guiding the placement of the FUS transducer to engage specific brain targets, holds great potential in enhancing the safety and effectiveness of tFUS therapy.

Influence of the Intracranial Contents on the Head Motion under Bone Conduction.

INTRODUCTION: The mechanism of non-osseous bone conduction pathways, involving the intracranial contents (ICC) of the skull, is still not well understood. This study aimed to investigate the influence of the ICC on the skull bone wave propagation, including dependence on stimulation location and coupling. METHODS: Three Thiel-embalmed whole-head cadaver specimens were studied before and after the removal of the ICC. Stimulation was via the electromagnetic actuators from commercial bone conduction hearing aids. Osseous pathways were sequentially activated by mastoid, forehead, and bone-anchored hearing aid location stimulation via a 5-Newton steel headband or percutaneously implanted screw. Non-osseous pathways were activated by stimulation on the eye and dura via a 5-Newton steel headband and a custom-made pneumatic holder, respectively. Under each test condition, the 3D motion of the superior skull bone was monitored at ∼200 points. RESULTS: The averaged response of the skull surface showed limited differences due to the removal of the ICC. In some isolated cases, the modal pattern on the skull surface showed a trend for an upshift (∼1/2 octave) in the observed natural frequencies for drained heads. This was also consistent with an observed trend for an upshift in the transition frequency in the estimated deformation across the lateral surfaces of the temporal bones. Such changes were consistent with the expected reduction in mass and damping due to the absence of the ICC. CONCLUSION: Overall, the ICC affect to a limited extent the motion of the skull bone, with a limited trend for a reduction of its natural frequencies.

Biomechanical Response of Head Surrogate With and Without the Helmet.

Measurements of brain deformations under injurious loading scenarios are actively sought. In this work, we report experimentally measured head kinematics and corresponding dynamic, two-dimensional brain simulant deformations in head surrogates under a blunt impact, with and without a helmet. Head surrogates used in this work consisted of skin, skull, dura, falx, tentorium, and brain stimulants. The head surrogate geometry was based on the global human body models consortium's head model. A base head surrogate consisting of skin-skull-brain was considered. In addition, the response of two other head surrogates, skin-skull-dura-brain, and skin-skull-dura-brain-falx-tentorium, was investigated. Head surrogate response was studied for sagittal and coronal plane rotations for impactor velocities of 1 and 3 m/s. Response of head surrogates was compared against strain measurements in PMHS. The strain pattern in the brain simulant was heterogenous, and peak strains were established within ∼30 ms. The choice of head surrogate affect the spatiotemporal evolution of strain. For no helmet case, peak MPS of ∼50-60% and peak MSS of ∼35-50% were seen in brain simulant corresponding to peak rotational accelerations of ∼5000-7000 rad/s2. Peak head kinematics and peak MPS have been reduced by up to 75% and 45%, respectively, with the conventional helmet and by up to 90% and 85%, respectively, with the helmet with antirotational pads. Overall, these results provide important, new data on brain simulant strains under a variety of loading scenarios-with and without the helmets.

Measurements of bone-conducted sound in the chinchilla external ear.

We measure bone-conduction (BC) induced skull velocity, sound pressure at the tympanic membrane (TM) and inner-ear compound-action potentials (CAP) before and after manipulating the ear canal, ossicles, and the jaw to investigate the generation of BC induced ear-canal sound pressures and their contribution to inner-ear BC response in the ears of chinchillas. These measurements suggest that in chinchilla: i.) Vibrations of the bony ear canal walls contribute significantly to BC-induced ear canal sound pressures, as occluding the ear canal at the bone-cartilaginous border causes a 10 dB increase in sound pressure at the TM (PTM) at frequencies below 2 kHz. ii.) The contributions to PTM of ossicular and TM motions when driven in reverse by BC-induced inner-ear sound pressures are small. iii.) The contribution of relative motions of the jaw and ear canal to PTM is small. iv.) Comparison of the effect of canal occlusion on PTM and CAP thresholds point out that BC-induced ear canal sound pressures contribute significantly to bone-conduction stimulation of the inner ear when the ear canal is occluded.

Effect of Direction and Frequency of Skull Motion on Mechanical Vulnerability of the Human Brain.

Strain energy and kinetic energy in the human brain were estimated by magnetic resonance elastography (MRE) during harmonic excitation of the head, and compared to characterize the effect of loading direction and frequency on brain deformation. In brain MRE, shear waves are induced by external vibration of the skull and imaged by a modified MR imaging sequence; the resulting harmonic displacement fields are typically "inverted" to estimate mechanical properties, like stiffness or damping. However, measurements of tissue motion from MRE also illuminate key features of the response of the brain to skull loading. In this study, harmonic excitation was applied in two different directions and at five different frequencies from 20 to 90 Hz. Lateral loading induced primarily left-right head motion and rotation in the axial plane; occipital loading induced anterior-posterior head motion and rotation in the sagittal plane. The ratio of strain energy to kinetic energy (SE/KE) depended strongly on both direction and frequency. The ratio of SE/KE was approximately four times larger for lateral excitation than for occipital excitation and was largest at the lowest excitation frequencies studied. These results are consistent with clinical observations that suggest lateral impacts are more likely to cause injury than occipital or frontal impacts, and also with observations that the brain has low-frequency (∼10 Hz) natural modes of oscillation. The SE/KE ratio from brain MRE is potentially a simple and powerful dimensionless metric of brain vulnerability to deformation and injury.

Comparison of Deformation Patterns Excited in the Human Brain In Vivo by Harmonic and Impulsive Skull Motion.

Noninvasive measurements of brain deformation in human participants in vivo are needed to develop models of brain biomechanics and understand traumatic brain injury (TBI). Tagged magnetic resonance imaging (tagged MRI) and magnetic resonance elastography (MRE) are two techniques to study human brain deformation; these techniques differ in the type of motion and difficulty of implementation. In this study, oscillatory strain fields in the human brain caused by impulsive head acceleration and measured by tagged MRI were compared quantitatively to strain fields measured by MRE during harmonic head motion at 10 and 50 Hz. Strain fields were compared by registering to a common anatomical template, then computing correlations between the registered strain fields. Correlations were computed between tagged MRI strain fields in six participants and MRE strain fields at 10 Hz and 50 Hz in six different participants. Correlations among strain fields within the same experiment type were compared statistically to correlations from different experiment types. Strain fields from harmonic head motion at 10 Hz imaged by MRE were qualitatively and quantitatively similar to modes excited by impulsive head motion, imaged by tagged MRI. Notably, correlations between strain fields from 10 Hz MRE and tagged MRI did not differ significantly from correlations between strain fields from tagged MRI. These results suggest that low-frequency modes of oscillation dominate the response of the brain during impact. Thus, low-frequency MRE, which is simpler and more widely available than tagged MRI, can be used to illuminate the brain's response to head impact.

Validation of subjective manual palpation using objective physiological recordings of the cranial rhythmic impulse during osteopathic manipulative intervention.

Intermediate (IM) band physiology in skin blood flow exhibits parallels with the primary respiratory mechanism (PRM) or cranial rhythmic impulse (CRI), controversial concepts of osteopathy in the cranial field (OCF). Owing to inconsistent manual palpation results, validity of evidence of PRM/CRI activity has been questionable. We therefore tried to validate manual palpation combining instrumented tracking and algorithmic objectivation of frequencies, amplitudes, and phases. Using a standard OCF intervention, cranial vault hold (CVH), two OCF experts palpated and digitally marked CRI frequencies in 25 healthy adults. Autonomic nervous system (ANS) activity in low frequency (LF) and IM band in photoplethysmographic (PPG) forehead skin recordings was probed with momentary frequency of highest amplitude (MFHA) and wavelet amplitude spectra (WAS) in examiners and participants. Palpation errors and frequency expectation bias during CVH were analyzed for phases of MFHA and CRI. Palpated CRI frequencies (0.05-0.08 Hz) correlated highly with mean MFHA frequencies with 1:1 ratio in 77% of participants (LF-responders; 0.072 Hz) and with 2:1 ratio in 23% of participants (IM-responders; 0.147 Hz). WAS analysis in both groups revealed integer number (harmonic) waves in (very) low and IM bands in > 98% of palpated intervals. Phase analyses in participants and examiners suggested synchronization between MFHA and CRI in a subset of LF-responders. IM band physiology in forehead PPG may offer a sensible physiological correlate of palpated CRI activity. Possible coordination or synchronization effects with additional physiological signals and between examiners and participants should be investigated in future studies.

Computational conjugate adaptive optics microscopy for longitudinal through-skull imaging of cortical myelin.

Myelination processes are closely related to higher brain functions such as learning and memory. While their longitudinal observation has been crucial to understanding myelin-related physiology and various brain disorders, skull opening or thinning has been required to secure clear optical access. Here we present a high-speed reflection matrix microscope using a light source with a wavelength of 1.3 µm to reduce tissue scattering and aberration. Furthermore, we develop a computational conjugate adaptive optics algorithm designed for the recorded reflection matrix to optimally compensate for the skull aberrations. These developments allow us to realize label-free longitudinal imaging of cortical myelin through an intact mouse skull. The myelination processes of the same mice were observed from 3 to 10 postnatal weeks to the depth of cortical layer 4 with a spatial resolution of 0.79 µm. Our system will expedite the investigations on the role of myelination in learning, memory, and brain disorders.

Cranial suture morphometry and mechanical response to loading: 2D vs. 3D assumptions and characterization.

Cranial sutures are complex soft tissue structures whose mechanics are often studied due to their link with bone growth in the skull. Researchers will often use a cross-sectional two-dimensional slice to define suture geometry when studying morphometry and/or mechanical response to loading. However, using a single cross section neglects the full suture complexity and may introduce significant errors when defining their form. This study aims to determine trends in suture path variability through skull thickness in a swine model and the implications of using a 'representative' cross section on mechanical modeling. To explore these questions, a mixture of quantitative analysis of computed tomography images and finite element models was used. The linear interdigitation and width of coronal and sagittal sutures were analyzed on offset transverse planes through the skull thickness. It was found that sagittal suture width and interdigitation were largely consistent through the skull thickness, whereas the coronal suture showed significant variation in both. The finite element study found that average values of displacement and strain were similar between the two-dimensionally variable and three-dimensionally variable models. Larger ranges and more complex distributions of strain were found in the three-dimensionally variable model. Outcomes of this study indicate that the appropriateness of using a representative cross section to describe suture morphometry and predict mechanical response should depend on specific research questions and goals. Two-dimensional approximations can be sufficient for less-interdigitated sutures and when bulk site mechanics are of interest, while taking the true three-dimensional geometry into account is necessary when considering spatial variability and local mechanical response.

Measurement and modeling of the mechanical impedance of human mastoid and condyle.

Bone conduction devices are used in audiometric tests, hearing rehabilitation, and communication systems. The mechanical impedance of the stimulated skull location affects the performance of the bone conduction devices. In the present study, the mechanical impedances of the mastoid and condyle were measured in 100 Chinese subjects aged from 22 to 67 years. The results show that the mastoid and condyle impedances within the same subject differ significantly and the impedance differences between subjects at the same stimulation position are mainly below the resonance frequency. The mechanical impedance of the mastoid is significantly influenced by age, and not related to gender or body mass index (BMI). While the mechanical impedance of the condyle is significantly affected by BMI, followed by gender, and not related to age. There are some differences in mastoid impedance between the Chinese and Western subjects. An analogy model predicts that the difference in mechanical impedance between the mastoid and condyle leads to a significant difference in the output force of the bone conduction devices. The results can be used to develop improved condyle and mastoid stimulators for the Chinese.

Wave propagation across the skull under bone conduction: Dependence on coupling methods.

This study is aimed at the quantitative investigation of wave propagation through the skull bone and its dependence on different coupling methods of the bone conduction hearing aid (BCHA). Experiments were conducted on five Thiel embalmed whole head cadaver specimens. An electromagnetic actuator from a commercial BCHA was mounted on a 5-Newton steel headband, at the mastoid, on a percutaneously implanted screw (Baha® Connect), and transcutaneously with a Baha® Attract (Cochlear Limited, Sydney, Australia), at the clinical bone anchored hearing aid (BAHA) location. Surface motion was quantified by sequentially measuring ∼200 points on the skull surface via a three-dimensional laser Doppler vibrometer (3D LDV) system. The experimental procedure was repeated virtually, using a modified LiUHead finite element model (FEM). Both experiential and FEM methods showed an onset of deformations; first near the stimulation area, at 250-500 Hz, which then extended to the inferior ipsilateral skull surface, at 0.5-2 kHz, and spread across the whole skull above 3-4 kHz. Overall, stiffer coupling (Connect versus Headband), applied at a location with lower mechanical stiffness (the BAHA location versus mastoid), led to a faster transition and lower transition frequency to local deformations and wave motion. This behaviour was more evident at the BAHA location, as the mastoid was more agnostic to coupling condition.

Simulation of soft tissue stimulation-Indication of a skull bone vibration mechanism in bone conduction hearing.

Soft tissue conduction has been proposed as an alternative to bone conduction (BC) for hearing vibrations applied at soft tissue positions at the human head. Arguments for soft tissue conduction originate primarily from experimental studies with stimulation applied to different positions such as the neck, the eye, and directly to the dura. To investigate the mechanism for hearing when stimulations are at soft tissue positions, experimental studies were replicated using the finite element model for BC research, the LiUHead. The vibrations at the cochlear promontory and the sound pressure in the cerebrospinal fluid (CSF) close to the inner ear were extracted from simulations in the LiUHead. The LiUHead simulations were able to replicate data in the literature of cochlear promontory vibration levels and CSF sound pressures with stimulation applied at the soft tissue positions and at the skin covered mastoid. It was shown that the mechanical point impedance of the soft tissue positions affected the output of the BC transducer at frequencies below 1 kHz. The LiUHead simulated cochlear promontory velocities predicted the soft tissue position's hearing thresholds reported in the literature within the inter-study range. This indicates that the hearing mechanism for stimulation at soft tissue positions equals the hearing mechanism for conventional BC hearing, and that soft tissue conduction is not an alternative hearing mechanism. Moreover, the simulations indicated that the CSF sound pressure is not an important pathway for BC hearing and that the CSF pressure is generated by the local skull bone vibrations.

Modeling implanted metals in electrical stimulation applications.

Objective. Metal implants impact the dosimetry assessment in electrical stimulation techniques. Therefore, they need to be included in numerical models. While currents in the body are ionic, metals only allow electron transport. In fact, charge transfer between tissues and metals requires electric fields to drive electrochemical reactions at the interface. Thus, metal implants may act as insulators or as conductors depending on the scenario. The aim of this paper is to provide a theoretical argument that guides the choice of the correct representation of metal implants in electrical models while considering the electrochemical nature of the problemApproach.We built a simple model of a metal implant exposed to a homogeneous electric field of various magnitudes. The same geometry was solved using two different models: a purely electric one (with different conductivities for the implant), and an electrochemical one. As an example of application, we also modeled a transcranial electrical stimulation (tES) treatment in a realistic head model with a skull plate using a high and low conductivity value for the plate.Main results. Metal implants generally act as electric insulators when exposed to electric fields up to around 100 V m-1and they only resemble a perfect conductor for fields in the order of 1000 V m-1and above. The results are independent of the implant's metal, but they depend on its geometry. tES modeling with implants incorrectly treated as conductors can lead to errors of 50% or more in the estimation of the induced fieldsSignificance.Metal implants can be accurately represented by a simple electrical model of constant conductivity, but an incorrect model choice can lead to large errors in the dosimetry assessment. Our results can be used to guide the selection of the most appropriate model in each scenario.

Developmentally interdependent stretcher-compressor relationship between the embryonic brain and the surrounding scalp in the preosteogenic head.

BACKGROUND: How developing brains mechanically interact with the surrounding embryonic scalp layers (ie, epidermal and mesenchymal) in the preosteogenic head remains unknown. Between embryonic day (E) 11 and E13 in mice, before ossification starts in the skull vault, the angle between the pons and the medulla decreases, raising the possibility that when the elastic scalp is directly pushed outward by the growing brain and thus stretched, it recoils inward in response, thereby confining and folding the brain. RESULTS: Stress-release tests showed that the E11-13 scalp recoiled and that the in vivo prestretch prerequisite for this recoil was physically dependent on the brain (pressurization at 77-93 Pa) and on actomyosin and elastin within the scalp. In scalp-removed heads, brainstem folding was reduced, and the spreading of ink from the lateral ventricle to the spinal cord that occurred in scalp-intact embryos (with >5 µL injection) was lost, suggesting roles of the embryonic scalp in brain morphogenesis and cerebrospinal fluid homeostasis. Under nonstretched conditions, scalp cell proliferation declined, while the restretching of the shrunken scalp rescued scalp cell proliferation. CONCLUSIONS: In the embryonic mouse head before ossification, a stretcher-compressor relationship elastically develops between the brain and the scalp, underlying their mechanically interdependent development.

Protocol for controlled cortical impact in human cerebral organoids to model traumatic brain injury.

Modeling traumatic brain injury (TBI) has been a challenge. Rodent and cellular models have provided relevant contributions despite their limitations. Here, we present a protocol for a TBI model based on the controlled cortical impact (CCI) performed on human cerebral organoids (COs), self-assembled 3D cultures that recapitulate features of the human brain. Here, we generate COs from iPSCs obtained from reprogrammed fibroblasts. For complete details on the use and execution of this protocol, please refer to Ramirez et al. (2021).

In Vivo Efficacy of Neutrophil-Mediated Bone Regeneration Using a Rabbit Calvarial Defect Model.

Reconstruction of bone due to surgical removal or disease-related bony defects is a clinical challenge. It is known that the immune system exerts positive immunomodulatory effects on tissue repair and regeneration. In this study, we evaluated the in vivo efficacy of autologous neutrophils on bone regeneration using a rabbit calvarial defect model. Methods: Twelve rabbits, each with two surgically created calvarial bone defects (10 mm diameter), were randomly divided into two groups; (i) single application of neutrophils (SA-NP) vs. SA-NP control, and (ii) repetitive application of neutrophils (RA-NP) vs. RA-NP control. The animals were euthanized at 4 and 8 weeks post-operatively and the treatment outcomes were evaluated by micro-computed tomography, histology, and histomorphometric analyses. Results: The micro-CT analysis showed a significantly higher bone volume fraction (bone volume/total volume) in the neutrophil-treated groups, i.e., median interquartile range (IQR) SA-NP (18) and RA-NP (24), compared with the untreated controls, i.e., SA-NP (7) and RA-NP (14) at 4 weeks (p < 0.05). Similarly, new bone area fraction (bone area/total area) was significantly higher in neutrophil-treated groups at 4 weeks (p < 0.05). Both SA-NP and RA-NP had a considerably higher bone volume and bone area at 8 weeks, although the difference was not statistically significant. In addition, immunohistochemical analysis at 8 weeks revealed a higher expression of osteocalcin in both SA-NP and RA-NP groups. Conclusions: The present study provides first hand evidence that autologous neutrophils may have a positive effect on promoting new bone formation. Future studies should be performed with a larger sample size in non-human primate models. If proven feasible, this new promising strategy could bring clinical benefits for bone defects to the field of oral and maxillofacial surgery.