The biomechanics of chewing and suckling in the infant: A potential mechanism for physiologic metopic suture closure.

Craniosynostosis is a condition with neurologic and aesthetic sequelae requiring invasive surgery. Understanding its pathobiology requires familiarity with the processes underlying physiologic suture closure. Animal studies have shown that cyclical strain from chewing and suckling influences the closure of cranial vault sutures, especially the metopic, an important locus of craniosynostosis. However, there are no human data correlating strain patterns during chewing and suckling with the physiologically early closure pattern of the metopic suture. Furthermore, differences in craniofacial morphology make it challenging to directly extrapolate animal findings to humans. Eight finite-element analysis (FEA) models were built from craniofacial computer tomography (CT) scans at varying stages of metopic suture closure, including two with isolated non-syndromic metopic craniosynostosis. Muscle forces acting on the cranium during chewing and suckling were simulated using subject-specific jaw muscle cross-sectional areas. Chewing and suckling induced tension at the metopic and sagittal sutures, and compressed the coronal, lambdoid, and squamous sutures. Relative to other cranial vault sutures, the metopic suture experienced larger magnitudes of axial strain across the suture and a lower magnitude of shear strain. Strain across the metopic suture decreased during suture closure, but other sutures were unaffected. Strain patterns along the metopic suture mirrored the anterior to posterior sequence of closure: strain magnitudes were highest at the glabella and decreased posteriorly, with minima at the nasion and the anterior fontanelle. In models of physiologic suture closure, increased degree of metopic suture closure correlated with higher maximum principal strains across the frontal bone and mid-face, a strain regime not observed in models of severe metopic craniosynostosis. In summary, our work provides human evidence that bone strain patterns from chewing and suckling correlate with the physiologically early closure pattern of the metopic suture, and that deviations from physiologic strain regimes may contribute to clinically observed craniofacial dysmorphism.

Simultaneous Coronoid Bone Grafting in Ballistic Facial Trauma Patients Undergoing Coronoidectomy.

Ballistic facial trauma can cause complex fractures and overlying soft tissue damage, with a zone of injury that extends beyond the bullet tract. Early skeletal fixation is indicated, and previous large case series describe the use of debrided bone fragments as 'spare part' grafts. This series presents the indications and techniques for simultaneous coronoid bone grafting in 2 patients who sustained a gunshot wound to the right midface and required coronoidectomy. The coronoid process was used as (1) an interposition graft in the lateral buttress of the right maxilla for stability, and (2) an onlay graft on the right inferior orbital rim for contour. Both patients did not have graft infection, extrusion, or malposition at the 1-month clinic follow-up. The coronoid process of the mandible is a viable, safe spare-part option, despite the possible location of the coronoid process within the zone of injury in the reconstruction of complex ballistic facial trauma.

The Role of Digital Surgical Planning and Surgical Guides in the Treatment of Unilateral Condylar Hyperplasia.

Unilateral condylar hyperplasia (UCH) results in facial asymmetry, malocclusion, and temporomandibular joint dysfunction. Treatment consists of both surgical and orthodontic intervention. A review was performed for 4 patients with UCH who underwent digital surgical planning (DSP)-assisted condylectomy. All patients were female, aged 14 to 35 years at the time of operation with facial asymmetry and class III malocclusion. None of the patients had prior treatment and all had perioperative orthodontic appliances to provide fixation and postoperative elastic therapy. All patients underwent DSP-guided condylectomy, and intraoperative surgical cutting guides were used for 3 of the patients. All had significant improvement in facial symmetry and occlusion. None had recurrence, and additional intervention has not been required. If UCH is recognized before marked secondary changes in the maxilla, mandible, and occlusion, future orthognathic surgery may be potentially obviated. Craniomaxillofacial surgeons should consider using DSP and surgical guides in the treatment of UCH.

Impact of Cleft Palate on Tongue-Based Upper Airway Obstruction in Pierre Robin Sequence: Implications for Mandibular Distraction Osteogenesis and Timing of Cleft Palate Repair.

INTRODUCTION: The objectives of this study are to analyze the impact of cleft palate (CP) on upper airway obstruction using polysomnography in patients with Pierre Robin Sequence (PRS) undergoing mandibular distraction osteogenesis (MDO) and subsequent CP repair. METHODS: A single-surgeon, retrospective chart review was performed of all patients with nonsyndromic PRS treated with MDO. Severity of upper airway obstruction was evaluated pre- and post-distraction via polysomnography. Details of MDO and CP repair were collected and any complications recorded. RESULTS: Twenty-one nonsyndromic PRS patients with CP and 6 patients without CP met inclusion criteria. There was no significant difference in predistraction apnea-hypopnea index between the 2 groups (53.4 ±â€Š42.1 versus 34.4 ±â€Š18.9; P = 0.3). Patients with CP had significantly higher predistraction SpO2 saturation (94.5 ±â€Š1.6% versus 91.0% ±â€Š4.8%; P = 0.01), SpO2 nadir (74.5% ±â€Š9.1% versus 63.6% ±â€Š11.6%; P = 0.03) and lower percentage time spent below 90% SpO2 (6.0% ±â€Š7.2% versus 23.6% ±â€Š29.9%; P = 0.04). The rate of oronasal fistulas formation was 38%. The time between MDO and CP repair was shorter for patients with complications (250.8 ±â€Š3.3 versus 370.8 ±â€Š191.9 days; P = 0.08). Five patients experienced relapse of respiratory difficulties after CP repair. CONCLUSIONS: The presence of CP in nonsyndromic PRS patients decreases the severity of obstructive sleep apnea by oxygen parameters on PSG. Palatal fistulas and relapse of respiratory distress are common complications of CP repair following MDO. Delaying CP repair may help to decrease complication rates.

BMP9-initiated osteogenic/odontogenic differentiation of mouse tooth germ mesenchymal cells (TGMCS) requires Wnt/ß-catenin signalling activity.

Teeth arise from the tooth germ through sequential and reciprocal interactions between immature epithelium and mesenchyme during development. However, the detailed mechanism underlying tooth development from tooth germ mesenchymal cells (TGMCs) remains to be fully understood. Here, we investigate the role of Wnt/ß-catenin signalling in BMP9-induced osteogenic/odontogenic differentiation of TGMCs. We first established the reversibly immortalized TGMCs (iTGMCs) derived from young mouse mandibular molar tooth germs using a retroviral vector expressing SV40 T antigen flanked with the FRT sites. We demonstrated that BMP9 effectively induced expression of osteogenic markers alkaline phosphatase, collagen A1 and osteocalcin in iTGMCs, as well as in vitro matrix mineralization, which could be remarkably blunted by knocking down ß-catenin expression. In vivo implantation assay revealed that while BMP9-stimulated iTGMCs induced robust formation of ectopic bone, knocking down ß-catenin expression in iTGMCs remarkably diminished BMP9-initiated osteogenic/odontogenic differentiation potential of these cells. Taken together, these discoveries strongly demonstrate that reversibly immortalized iTGMCs retained osteogenic/odontogenic ability upon BMP9 stimulation, but this process required the participation of canonical Wnt signalling both in vitro and in vivo. Therefore, BMP9 has a potential to be applied as an efficacious bio-factor in osteo/odontogenic regeneration and tooth engineering. Furthermore, the iTGMCs may serve as an important resource for translational studies in tooth tissue engineering.

Predictors of Opioid Prescription After Orthognathic Surgery in Opioid Naive Adults From a Large Database.

BACKGROUND: Orthognathic surgery often requires postoperative opioid pain management. The goal of this study was to examine opioid prescribing patterns in adults after orthognathic surgery and to analyze factors associated with high-dose postoperative opioid administration and persistent opioid use. METHODS: We included opioid naive adults in the IBM MarketScan Databases who had undergone orthognathic surgery from 2003 to 2017. Three outcomes were examined: presence of a perioperative outpatient opioid claim; total oral morphine milliequivalents (MMEs) in the perioperative period; and persistent opioid use. Univariate analysis and multiple regression were used to determine associations between the outcomes and independent variables. RESULTS: Our study yielded a cohort of 8163 opioid naive adults, 45.6% of whom had an opioid claim in the perioperative period. The average prescribed MMEs in the perioperative period was 466 MMEs total, and 66 MMEs daily. Of patients with an opioid claim, 17.9% had persistent opioid use past 90 days. The presence of a complication was a predictor of having an opioid claim (P<0.001). Increasing age (P<0.001) and days hospitalized (P < 0.001) were associated with increased opioid usage. Persistent opioid use was associated with being prescribed more than 600 MMEs in the perioperative period (P < 0.001), as well as increasing age and days hospitalized. Interestingly, patients undergoing double-jaw surgery did not have significantly more opioids prescribed than those undergoing single-jaw surgery. CONCLUSIONS: Prescription opioids are relatively uncommon after jaw surgery, although 17.9% of patients continue to use opioids beyond 3 months after surgery. Predictors of persistent opioid use in this population include the number of days hospitalized, increasing age, and increasing amount of opioid prescribed postoperatively.

Custom Alloplastic Temporomandibular Joint Reconstruction: Expanding Reconstructive Horizons.

Custom alloplastic temporomandibular joint (TMJ) reconstruction has been well established for the management of end-stage TMJ disease. However, its use in congenital TMJ deformities is limited. Here, the authors present initial outcomes of skeletally mature patients who underwent custom alloplastic TMJ reconstruction and simultaneous orthognathic surgery.A retrospective case series of patients who underwent custom alloplastic TMJ reconstruction concurrent with orthognathic surgery between 2014 and 2019 was completed. Functional, aesthetic and orthodontic outcomes as well as complications were recorded.Seven TMJs in 5 skeletally mature patients (4 female, 1 male, ages 16-30) (2 bilateral, 3 unilateral) were replaced. All but 1 patient had previous attempts at reconstructive surgery with poor results. All cases were prepared using virtual surgical planning and underwent concomitant maxillomandibular orthognathic surgery. All patients demonstrated improved post-operative occlusions. Four of 5 patients achieved >30 millimeters of post-operative MIO. Complications included ear canal perforation and facial nerve dysfunction.There were no infections or other implant-related complications. Mean follow up was 2 years and 15 days. Alloplastic TMJ reconstruction at the time of skeletal maturity for patients with congenital mandibular TMJ defects is an alternative to existing management options. Further long-term prospective outcomes studies are ongoing.

Airway Morphological Changes in Pierre Robin Sequence: A Retrospective Study.

OBJECTIVE: To investigate airway morphology changes in patients with Pierre Robin sequence (PRS) pre-/post-mandibular distraction osteogenesis (MDO) and to compare morphologic changes to age-matched controls. DESIGN: Retrospective case-control study. SETTING: Urban, academic, tertiary medical center. PATIENTS, PARTICIPANTS: Fifteen patients with PRS after MDO to relieve upper airway obstruction (UAO) (2008-2018); age-matched controls for post-MDO patients. INTERVENTIONS: Mandibular distraction osteogenesis, curvilinear internal mandibular distractors. MAIN OUTCOME MEASURES: (1) Physiologic improvement after MDO (apnea-hypopnea index; minimum oxygen saturation); (2) airway size (volume, surface area, length, mean/minimum cross-sectional area), shape (lateral:anterior-posterior ratio, cross-sectional area ratios, uniformity, sphericity), and changes with MDO; and (3) post-MDO airway size, shape versus age-matched controls. RESULTS: Airway size increased after MDO (volume, P = .01; surface area, P = .02; length, P = .01), as did cross-sectional area (mean, P = .02; minimum, P = .02; minimum retropalatal, P = .05, mid-retroglossal, P = .02). Post-MDO PRS airways were larger than controls (volume, P < .01; surface area, P < .01; length, P < .01, cross-sectional area, P = .03). Airway shape remained nonuniform and flat post-MDO; control airways were round. Two syndromic patients required repeat MDO and had subphysiologic post-MDO airway cross-sectional area. Post-MDO PRS patients with supraphysiologic cross-sectional area along the entire airway had no UAO recurrence. CONCLUSIONS: In this small, heterogenous patient sample, MDO increases airway size, may preferentially affect the retropalatal airway, and often results in supraphysiologic airway dimensions. These retropalatal changes may be important in relieving severe UAO in patients with PRS. Generalizability of our results is limited by small cohort size and patient heterogeneity.

Does Mandibular Distraction Vector Influence Airway Volumes and Outcome?

PURPOSE: The goal of mandibular distraction in the Pierre-Robin sequence is to maximally expand the oropharyngeal airway. It has been hypothesized that a steep oblique distraction vector might allow greater airway enlargement compared with horizontal distraction. This study compared vector orientation in relation to airway volume and overall clinical outcome. MATERIALS AND METHODS: Micrognathic infants who underwent mandibular distraction with sufficient computed tomographic data were retrospectively reviewed. Demographic, diagnostic, perioperative, and distraction data were recorded. Groups were separated based on distraction vector (group 1, horizontal; group 2, oblique). Airway and mandibular volumes were measured using Mimics (Materialise, Leuven, Belgium). Morphologic and outcomes data were analyzed. Statistics involved 2-tailed t test, Pearson correlation, and analysis of covariance (ANCOVA). RESULTS: Mean age at distraction was 40 days, with devices maintained for 82 days on average. Fifty percent of patients were girls and 65% had cleft palate. Forty computed tomograms were analyzed. Airway (1,234 vs 3,501 mm3; P < .01) and mandibular (5,457 vs 11,827 mm3; P < .01) volumes, minimal airway area (12.5 vs 63.7 mm2; P < .01), and posterior airway space distance (2.3 vs 9.8 mm; P = .04) were significantly increased after distraction. Patients also had clinically improved sleep studies after distraction (apnea hypopnea index, 51.3 vs 5.5; P < .01). Vector analysis showed an average of 5.3° and 14.0° in groups 1 and 2, respectively (n = 10 each). Intergroup analysis showed a trend toward increased airway volume in horizontal vectors (548 vs 255% of preoperative volume; P = .058), with slightly longer distraction length (20.3 vs 16.6 mm; P = .17). However, ANCOVA regression analysis showed no difference in the relation between vector and length. Other morphologic data and sleep study outcomes (apnea hypopnea index, 7.0 vs 3.9; P = .09) also were not statistically different between groups. Longer lengths of distraction correlated with narrower anterior mandibular angle and longer mandibular body length. CONCLUSIONS: Substantial airway enlargement occurs after mandibular distraction. Final airway volumes were similar between groups regardless of vector, which was confirmed by multivariate ANCOVA regression. The 2 methods achieved airway stabilization, with clinical outcomes similar between the 2 groups.

The Pierre Robin Mandible is Hypoplastic and Morphologically Abnormal.

BACKGROUND: For Pierre Robin sequence (PRS) patients, there is incomplete characterization of 3D differences and effects of mandibular distraction osteogenesis (MDO) on the mandible compared to normal controls. METHODS: PRS infants who underwent MDO at 2 craniofacial referral centerals with pre- and postoperative computed tomography (CT) scans were identified. A group of age-matched control patients with CTs were identified in the PACS database. Demographic and perioperative data were recorded. Mandibular lengths, angles, and volumes were measured. Morphologic and outcomes data were analyzed in a case-control comparison. RESULTS: Sixty-three CT scans were analyzed. Fifteen pre-op PRS patient and 15 control CTs were well matched in terms of age and sex. Mandibular volume (78%), ramus length (87%), and body length (95%) were all decreased in the PRS patients. Anterior symphyseal angle (84%) was significantly reduced in PRS patients while mandibular angle (102%) was maintained. Eighteen post-op PRS patient and 15 control CTs were well matched in terms of age and gender. Mandibular volumes (106%) were normalized following distraction with shorter mandibular rami (88%) and longer mandibular bodies (109%). Postoperatively, mandibular angle (100%) and anterior symphyseal angle (99%) were ultimately indistinguishable from controls. CONCLUSIONS: The mandible in PRS is dysmorphic compared to age-matched controls. Overall, they have a smaller volume, shorter ramus, and an obtuse symphyseal angle. MDO improves mandibular volume and normalizes the symphyseal angle, but results in a longer mandibular body and shorter mandibular ramus.

Predictive Soft Tissue Airway Volume Analysis in Mandibular Distraction: Pushing The Envelope in Surgical Planning for Obstructive Sleep Apnea.

Three-dimensional computed tomography has been used in both preoperative planning of mandibular distraction osteogenesis and in the evaluation of postoperative resolution of tongue-based airway obstruction. The authors present a case report using software to predict postdistraction airway volume during virtual surgical planning (VSP) of mandibular distraction osteogenesis in a 7 year old. The predicted increase in airway volume derived from VSP was 33.57% (1716 mm(3) preoperatively to 2292 mm(3) postvirtual distraction). Based on the three-dimensional computed tomography, the actual airway volume increased to 2211 mm(3) postoperatively, a 28.85% increase.The implications of this advancing technology are far-reaching. An illustrative case is presented herein to demonstrate the efficacy of the airway prediction and its limitations. The authors believe that, with continued investigation, this novel approach may be a standard feature of all VSP sessions for the treatment of tongue-based airway obstruction.

Odontogenic myxoma of the face: mimicry of cherubism.

The present study is a case report of a 3-year-old girl who was referred to our clinic with the clinical features of cherubism. A locally aggressive tumor was diffusely infiltrating the maxilla and mandible. At 4 years after resection, our patient has not demonstrated any signs of recurrence, which might point to a role for adjunctive chemotherapy, in this case imatinib (Gleevec), for odontogenic myxoma.

In-House 3D Printing and Model Processing Technique for Creating High-Fidelity Transparent Craniofacial Models.

SUMMARY: The use of high-fidelity stereolithographic models that accurately reflect patient-specific pathology has become commonplace in craniofacial surgery. Multiple studies have reported the use of commercially available three-dimensional (3D) printers that allow medical centers with limited resources to reconstruct 3D models comparable to industry-made counterparts. However, most models are printed using only a single filament, which portrays the surface craniofacial anatomy, but fails to highlight relevant intraosseous structures. This presents a significant limitation when used for preoperative planning and intraoperative guidance in surgical procedures requiring osteotomies, where knowledge of the precise location of critical structures is paramount to avoid injury. The authors report a novel technique for creating transparent 3D models of relevant intraosseous craniofacial anatomy at a cost that mitigates the financial burden of industrial 3D model or industrial 3D printer acquisition. Cases are presented to demonstrate the diverse applications of this technique, with accurate display of the tooth roots, the inferior alveolar nerve, and the optic nerve, to aid in preoperative planning of osteotomies. This technique enables production of low-cost, high-fidelity transparent 3D models with applications in preoperative planning for craniofacial surgery.

Bone morphogenetic proteins in craniofacial surgery: current techniques, clinical experiences, and the future of personalized stem cell therapy.

Critical-size osseous defects cannot heal without surgical intervention and can pose a significant challenge to craniofacial reconstruction. Autologous bone grafting is the gold standard for repair but is limited by a donor site morbidity and a potentially inadequate supply of autologous bone. Alternatives to autologous bone grafting include the use of alloplastic and allogenic materials, mesenchymal stem cells, and bone morphogenetic proteins. Bone morphogenetic proteins (BMPs) are essential mediators of bone formation involved in the regulation of differentiation of osteoprogenitor cells into osteoblasts. Here we focus on the use of BMPs in experimental models of craniofacial surgery and clinical applications of BMPs in the reconstruction of the cranial vault, palate, and mandible and suggest a model for the use of BMPs in personalized stem cell therapies.

Fracture Fixation Technique and Chewing Side Impact Jaw Mechanics in Mandible Fracture Repair.

Lower jaw (mandible) fractures significantly impact patient health and well-being due to pain and difficulty eating, but the best technique for repairing the most common subtype-angle fractures-and rehabilitating mastication is unknown. Our study is the first to use realistic in silico simulation of chewing to quantify the effects of Champy and biplanar techniques of angle fracture fixation. We show that more rigid, biplanar fixation results in lower strain magnitudes in the miniplates, the bone around the screws, and in the fracture zone, and that the mandibular strain regime approximates the unfractured condition. Importantly, the strain regime in the fracture zone is affected by chewing laterality, suggesting that both fixation type and the patient's post-fixation masticatory pattern-ipsi- or contralateral to the fracture- impact the bone healing environment. Our study calls for further investigation of the impact of fixation technique on chewing behavior. Research that combines in vivo and in silico approaches can link jaw mechanics to bone healing and yield more definitive recommendations for fixation, hardware, and postoperative rehabilitation to improve outcomes. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Macaca mulatta is a good model for human mandibular fixation research.

Biomechanical and clinical studies have yet to converge on the optimal fixation technique for angle fractures, one of the most common and controversial fractures in terms of fixation approach. Prior pre-clinical studies have used a variety of animal models and shown abnormal strain environments exacerbated by less rigid (single-plate) Champy fixation and chewing on the side opposite the fracture (contralateral chewing). However, morphological differences between species warrant further investigation to ensure that these findings are translational. Here we present the first study to use realistically loaded finite-element models to compare the biomechanical behaviour of human and macaque mandibles pre- and post-fracture and fixation. Our results reveal only small differences in deformation and strain regimes between human and macaque mandibles. In the human model, more rigid biplanar fixation better approximated physiologically healthy global bone strains and moments around the mandible, and also resulted in less interfragmentary strain than less rigid Champy fixation. Contralateral chewing exacerbated deviations in strain, moments and interfragmentary strain, especially under Champy fixation. Our pre- and post-fracture fixation findings are congruent with those from macaques, confirming that rhesus macaques are excellent animal models for biomedical research into mandibular fixation. Furthermore, these findings strengthen the case for rigid biplanar fixation over less rigid one-plate fixation in the treatment of isolated mandibular angle fractures.

Use of resorbable implants for mandibular fixation: a systematic review.

Titanium plating is recognized as the criterion standard for the treatment of mandibular fractures and osteotomies. Use of resorbable implants is well documented in the literature for a range of craniofacial fractures. However, no clear review exists of the use of resorbable implants on the mandible. In this systematic review, we searched MEDLINE/PubMed and the Cochrane Database for studies of resorbable mandibular fixation. Two independent reviewers analyzed the search results using specific inclusion/exclusion criteria. Twenty-two articles detailing 19 studies, including 1 randomized controlled trial were analyzed in this study. These studies included fixation of mandibular fractures at various locations or fixation of bilateral sagittal split osteotomies. Overall, we found a total of 326 patients treated with resorbable plates and screws and 112 patients treated with resorbable screws alone. Analysis of these studies indicates that several material types are used in resorbable mandibular implants, including poly-L-lactic acid (PLLA) and 70% poly-L-lactic acid/30% poly-D,L-lactic acid (PLLA 70/PDLLA 30), coming from at least 10 different manufacturers. Mean follow-up ranged from 3 to 348 weeks. Based on the reported data, we found a total of 14 to 15 infections, 2 foreign body reactions, 7 malocclusions, 8 malunions, and 8 to 10 premature removals in the plate group and 1 foreign body reaction and 2 malocclusions in the screws-only group. These results should be interpreted in the context of the patient selection criteria in the studies. This systematic review demonstrates the need for further randomized controlled trials in this area and concludes with such a study design.

Design and fabrication of a generic 3D-printed silicone unilateral cleft lip and palate model.

The complexity of plastic surgery procedures often requires visualization of the anatomy in three dimensions and therefore demands the development of new and innovative teaching methods. This work describes the development and manufacture of a 3D silicone cleft lip and palate (CLP) model evaluated by surgical residents on its similarity to the biological model. Thirty unilateral CLP models were created and distributed to residents at two different institutions. The model was based on an adult CT scan that was manipulated to resemble an infant with a complete unilateral CLP. This digital model was directly printed in silicone elastomer pieces and later assembled. The residents rated the model based on its realistic value as well as whether or not they felt it improved their surgical technique. Twenty residents used the model to simulate a CLP repair. The structure of the model was rated as fairly realistic while both the material and assembly of the model require improvement in subsequent manufacturing. Post simulation, residents rated the model highly for how accurately it simulated the surgical procedure. An accurate 3D silicone unilateral cleft lip and palate replica was successfully created for educational purposes. This new approach combines a flexible generic design with automated manufacture.

A pH-Triggered, Self-Assembled, and Bioprintable Hybrid Hydrogel Scaffold for Mesenchymal Stem Cell Based Bone Tissue Engineering.

Effective bone tissue engineering can restore bone and skeletal functions that are impaired by traumas and/or certain medical conditions. Bone is a complex tissue and functions through orchestrated interactions between cells, biomechanical forces, and biofactors. To identify ideal scaffold materials for effective mesenchymal stem cell (MSC)-based bone tissue regeneration, here we develop and characterize a composite nanoparticle hydrogel by combining carboxymethyl chitosan (CMCh) and amorphous calcium phosphate (ACP) (designated as CMCh-ACP hydrogel). We demonstrate that the CMCh-ACP hydrogel is readily prepared by incorporating glucono δ-lactone (GDL) into an aqueous dispersion or rehydrating the acidic freeze-dried nanoparticles in a pH-triggered controlled-assembly fashion. The CMCh-ACP hydrogel exhibits excellent biocompatibility and effectively supports MSC proliferation and cell adhesion. Moreover, while augmenting BMP9-induced osteogenic differentiation, the CMCh-ACP hydrogel itself is osteoinductive and induces the expression of osteoblastic regulators and bone markers in MSCs in vitro. The CMCh-ACP scaffold markedly enhances the efficiency and maturity of BMP9-induced bone formation in vivo, while suppressing bone resorption occurred in long-term ectopic osteogenesis. Thus, these results suggest that the pH-responsive self-assembled CMCh-ACP injectable and bioprintable hydrogel may be further exploited as a novel scaffold for osteoprogenitor-cell-based bone tissue regeneration.