Complete Bone Regeneration Research Articles

The influence of connective tissue grafting on the reconstruction of a missing facial bone wall using immediate implant placement and simultaneous bone reconstruction: a retrospective long-term cohort study

PurposeThis retrospective cohort study evaluates the influence of connective tissue grafts (CTG) on bone regeneration at implant sites with total loss of the buccal bone wall treated with flapless immediate implant placement (IIP) and reconstruction with autogenous bone chips (AB) within a follow-up of up to 13 years.MethodsSixty implants were inserted in 55 patients in sites with total loss of the buccal bone wall between 2008 and 2021. The implants were inserted and the buccal gaps were grafted by AB. A subgroup of 34 sites was grafted additionally with CTG using tunnel technique. Primary outcome was the vertical bone regeneration in height and thickness. Secondary outcome parameters were interproximal marginal bone level, recession, soft tissue esthetics (PES), width of keratinized mucosa (KMW) and probing depths (PPD).ResultsMean follow-up period was 60.8 months. In 55 sites a complete vertical bone regeneration was documented. The mean buccal bone level increased by 10.6 mm significantly. The thickness of the buccal bone wall ranged between 1.7 and 1.9 mm, and was significantly thicker in sites without CTG. Interproximal marginal bone level was at implant shoulder level. The mean recession improved significantly by 1.2 mm. In sites with CTG, recessions and PES improved significantly more.ConclusionsAdditional CTG in extraction sites with total buccal bone loss followed by IIP with simultaneous AB grafting led to improved PES and recession, but also to a thinner buccal bone wall compared to sites grafted just with AB.Graphical

Research on the model of mandibular alveolar bone defect in rabbits

Objectives: The purpose of this study was to create an animal model of a mandibular alveolar bone defect without compromising the animal’s well-being. Materials and methods: A total of 24 New Zealand white rabbits underwent surgery to create mandibular alveolar bone defects. The animals were sacrificed at 2, 4, 6, 8, 10, and 12 weeks post-surgery. To assess bone regeneration at the surgical site, radiography, dental cone-beam computed tomography (CT), and histological examination using Hematoxylin and Eosin staining were performed on the skull. Results: A straightforward and easily executable method was devised to create the rabbit mandibular alveolar defect model. After 10 weeks, complete soft tissue and bone regeneration were observed. X-ray and cone-beam CT evaluations demonstrated a progressive increase in bone density from weeks 2 to 12. Histological examination revealed that the alveolar bone structure was formed incrementally at the surgical site. The bone and connective tissue had filled the defect after 8 weeks. Conclusion: The creation of a model of mandibular alveolar bone defects in rabbits is a straightforward process that can be used to assess the regeneration of alveolar bone at the defect site. This animal model can serve as the foundation for tests to evaluate the capacity of biomaterials to regenerate the alveolar bone Key words: mandibular alveolar bone, Alveolar bone defects, animal models, bone regenerative medicine, tissue engineering.

Electrospun photocrosslinkable hydrogel fibrous membrane with metal ion trapping capability as an artificial periosteum to promote bone regeneration

The periosteum plays a crucial role in both bone development and the healing process of bone fractures. However, few studies have focused on developing artificial periosteum due to the complexity of its construction and the biological risks for clinical practice. To address this issue, we proposed a strategy for the fabrication of a photocrosslinkable natural hydrogel nanofibrous membrane (SFMA-Lap@AcBP) based on methacrylated silk fibroin (SFMA), photoinitiator (Lap), acrylate bisphosphonate (AcBP) through combining electrospinning technology with hydrogel, mimicking the structure and function of periosteum to promote bone regeneration. AcBP were covalently attached to the SFMA hydrogel nanofibrous membrane via conjugation. With the degradation of SFMA-Lap@AcBP hydrogel nanofibrous membrane, the released BP-grafted derivates could promote bone regeneration. Moreover, SFMA-Lap@AcBP hydrogel membranes were found to be able to trap metal ions such as Mg2+ and Ca2+in vivo, which might play a synergistic role in inducing complete bone regeneration. Furthermore, the hydrogel membranes had excellent cytocompatibility. They could imitate the microenvironment of the extracellular matrix, thereby offering structural and biochemical cues for the adhesion, proliferation, and differentiation of cells, without the need of exogenous cells or inductive growth factors, resulting in a facilitated osteogenesis. After implanting membranes into a cranial periosteal and bone defect in rats, both the amount and quality of new bone in the SFMA-Lap@AcBP group were found to be higher than those in the other groups. Therefore, the hydrogel membrane bionic periosteum was efficient and versatile in inducing bone regeneration, providing a potential strategy to address clinical issues.

Kaempferol-loaded bioactive glass-based scaffold for bone tissue engineering: in vitro and in vivo evaluation

Due to the increasing prevalence of bone disorders among people especially in average age, the future of treatments for osseous abnormalities has been illuminated by scaffold-based bone tissue engineering. In this study, in vitro and in vivo properties of 58S bioactive glass-based scaffolds for bone tissue engineering (bare (B.SC), Zein-coated (C.SC), and Zein-coated containing Kaempferol (KC.SC)) were evaluated. This is a follow-up study on our previously published paper, where we synthesized 58S bioactive glass-based scaffolds coated with Kaempferol-loaded Zein biopolymer, and characterized from mostly engineering points of view to find the optimum composition. For this aim, in vitro assessments were done to evaluate the osteogenic capacity and biological features of the scaffolds. In the in vivo section, all types of scaffolds with/without bone marrow-derived stem cells (BMSC) were implanted into rat calvaria bone defects, and potential of bone healing was assessed using imaging, staining, and histomorphometric analyses. It was shown that, Zein-coating covered surface cracks leading to better mechanical properties without negative effect on bioactivity and cell attachment. Also, BMSC differentiation proved that the presence of Kaempferol caused higher calcium deposition, increased alkaline phosphatase activity, bone-specific gene upregulation in vitro. Further, in vivo study confirmed positive effect of BMSC-loaded KC.SC on significant new bone formation resulting in complete bone regeneration. Combining physical properties of coated scaffolds with the osteogenic effect of Kaempferol and BMSCs could represent a new strategy for bone regeneration and provide a more effective approach to repairing critical-sized bone defects.

Biomimetic hematoma delivers an ultra-low dose of rhBMP-2 to successfully regenerate large femoral bone defects in rats.

Successful repair of large bone defects remains a clinical challenge. Following fractures, a bridging hematoma immediately forms as a crucial step that initiates bone healing. In larger bone defects the micro-architecture and biological properties of this hematoma are compromised, and spontaneous union cannot occur. To address this need, we developed an ex vivo Biomimetic Hematoma that resembles naturally healing fracture hematoma, using whole blood and the natural coagulants calcium and thrombin, as an autologous delivery vehicle for a very reduced dose of rhBMP-2. When implanted into a rat femoral large defect model, complete and consistent bone regeneration with superior bone quality was achieved with 10-20× less rhBMP-2 compared to that required with the collagen sponges currently used. Moreover, calcium and rhBMP-2 demonstrated a synergistic effect enhancing osteogenic differentiation, and fully restored mechanical strength 8weeks after surgery. Collectively, these findings suggest the Biomimetic Hematoma provides a natural reservoir for rhBMP-2, and that retention of the protein within the scaffold rather than its sustained release might be responsible for more robust and rapid bone healing. Clinically, this new implant, using FDA-approved components, would not only reduce the risk of adverse events associated with BMPs, but also decrease treatment costs and nonunion rates.

Osteoblast-Mediated Resorption of Porous Bioactive SCPC Granules Enhances Bone Regeneration in Human Extraction Sockets

Bone graft materials are widely used in orthopedic and maxillofacial surgeries. The controlled resorbability of the graft material is essential for bone regeneration. Hydroxyapatite and biphasic calcium phosphate bone grafts have poor resorption and limited bone conductive effects. Histology analyses of bone biopsy from SCPC grafted human extraction sockets showed complete bone regeneration and graft resorption in absence of osteoclasts and macrophages. The hypothesis of the present study is that bioactive SCPC inhibits osteoclast’s activity due to the presence of resorbable silica phase in the material. Our objective is to analyze the effect of SCPC dissolution products on the resorption activity of osteoclasts. The conditioned medium was prepared by immersion of SCPC resorbable bioactive SCPC porous granules (Shefabone, Inc, USA) in cell culture medium at various ratios at 37°C for 3 days. The concentration of Si ions released from the SCPC granules into cell culture medium was measured using ICP-OES. Osteoclast precursors derived from human bone marrow were seeded on bone slices and cultured in the conditioned medium containing 10% FBS and osteoclast induction factors. Osteoclast differentiation and resorption were evaluated by TRAP staining and measurement of the volume of resorption pits on the bone slices. Mature multinuclear giant TRAP-positive osteoclasts were observed on the bone substrates after 14 days incubation in control medium containing osteoclast induction factors. In conditioned medium, the number of multinuclear TRAP-positive cells was significantly decreased as the concentration of SCPC dissolved silica increased. The dissolution of silica from SCPC into the culture medium correlates well with down regulation of osteoclast differentiation and the rapid bone regeneration in human bone defects.

ODONTOGENIC KERATOCYST IN THE MAXILLA: CASE REPORT

A 32-year-old female patient was referred to the oral and maxillofacial surgery service with pain in the jaw for approximately 1 year. On extraoral and intraoral examination, there were no apparent changes or asymmetry. Cone beam computed tomography evidenced an extensive cystic lesion in the left maxillary bone, hypodense, with well-defined limits, extending to the maxillary sinus and involving the impacted tooth 28. Surgical treatment was performed under general anesthesia through enucleation followed by curettage of the entire lesion and removal of the involved impacted tooth. Histopathologic analysis of the specimen resulted in the diagnosis of odontogenic keratocyst. At 10-day follow-up, the surgical site showed adequate tissue repair process. In the postoperative clinical and radiographic follow-up at 1 year and 2 months, a complete bone regeneration was observed and there was no signs of lesion recurrence.

SYNCHRONOUS DENTIGEROUS CYST AND ODONTOGENIC KERATOCYST IN MANDIBLE: CASE REPORT

Odontogenic keratocyst and dentigerous cyst are noninflammatory odontogenic cysts and account for 10% to 20% and 20% of all odontogenic cysts, respectively. We report an uncommon synchronous occurrence of both lesions in a 46-year-old White man. The patient presented with bilateral asymptomatic unilocular well-demarcated radiolucent lesions of the mandible. The right lesion measured 2.5 cm and involved the crown of the third molar. The left lesion measured 4.0 cm, had scalloped margins, and extended apically along the root to the lower margin of the jaw. The left second molar root was reabsorbed. Large-needle aspirations showed yellow liquid on the right side and white liquid on the left. Lesions were enucleated and tooth extraction was performed. A titanium plate was placed on the left side. Histopathologic examination confirmed the diagnosis of dentigerous cyst on the right side and odontogenic keratocyst on the left side. After 9 months of follow-up, there was complete bone regeneration with no recurrence.

SURGICAL TREATMENT OF CALCIFYING ODONTOGENIC CYST—CASE REPORT

An 18-year-old male patient reporting swelling in the mouth was referred to the oral and maxillofacial surgery service. On intraoral examination, the presence of a bulge along the bottom of the posterior right mandibular vestibule was noted, with normal color and a smooth surface. Panoramic radiographic examination revealed a multilocular radiolucent intraosseous lesion, with well-defined limits and radiopaque structure inside. Cone beam computed tomography showed root apices resorption of teeth 45, 46, and 47; expansion of the buccal and lingual cortical bone; and close contact of the lesion with the inferior alveolar vasculature-nervous bundle. Incisional biopsy revealed a calcifying odontogenic cyst. Surgical treatment was performed through enucleation, followed by curettage of the intraosseous lesion, under general anesthesia. The 1-year postoperative follow-up showed complete bone regeneration and there were no signs of recurrence. An 18-year-old male patient reporting swelling in the mouth was referred to the oral and maxillofacial surgery service. On intraoral examination, the presence of a bulge along the bottom of the posterior right mandibular vestibule was noted, with normal color and a smooth surface. Panoramic radiographic examination revealed a multilocular radiolucent intraosseous lesion, with well-defined limits and radiopaque structure inside. Cone beam computed tomography showed root apices resorption of teeth 45, 46, and 47; expansion of the buccal and lingual cortical bone; and close contact of the lesion with the inferior alveolar vasculature-nervous bundle. Incisional biopsy revealed a calcifying odontogenic cyst. Surgical treatment was performed through enucleation, followed by curettage of the intraosseous lesion, under general anesthesia. The 1-year postoperative follow-up showed complete bone regeneration and there were no signs of recurrence.

In vitro and in vivo characterization of a novel tricalcium silicate-based ink for bone regeneration using laser-assisted bioprinting

Grafts aside, current strategies employed to overcome bone loss still fail to reproduce native tissue physiology. Among the emerging bioprinting strategies, laser-assisted bioprinting (LAB) offers very high resolution, allowing designing micrometric patterns in a contactless manner, providing a reproducible tool to test ink formulation. To this date, no LAB associated ink succeeded to provide a reproducible ad integrum bone regeneration on a murine calvaria critical size defect model. Using the Conformité Européenne (CE) approved BioRoot RCS® as a mineral addition to a collagen-enriched ink compatible with LAB, the present study describes the process of the development of a solidifying tricalcium silicate-based ink as a new bone repair promoting substrates in a LAB model. This ink formulation was mechanically characterized by rheology to adjust it for LAB. Printed aside stromal cells from apical papilla (SCAPs), this ink demonstrated a great cytocompatibility, with significant in vitro positive impact upon cell motility, and an early osteogenic differentiation response in the absence of another stimulus. Results indicated that the in vivo application of this new ink formulation to regenerate critical size bone defect tends to promote the formation of bone volume fraction without affecting the vascularization of the neo-formed tissue. The use of LAB techniques with this ink failed to demonstrate a complete bone repair, whether SCAPs were printed or not of at its direct proximity. The relevance of the properties of this specific ink formulation would therefore rely on the quantity applied in situ as a defect filler rather than its cell modulation properties observed in vitro. For the first time, a tricalcium silicate-based printed ink, based on rheological analysis, was characterized in vitro and in vivo, giving valuable information to reach complete bone regeneration through formulation updates. This LAB-based process could be generalized to normalize the characterization of candidate ink for bone regeneration.

Treatment of primary molar utilizing lesion sterilization and tissue repair: a case report

Aim: Non-instrumental endodontic therapy has stood out for being a minimal intervention approach that uses a mixture of antibiotics to disinfect the root canals. The purpose of this case report was to describe the treatment and 36-month follow-up of a deciduous necrotic molar using the modified technique of “Injury Sterilization and Tissue Repair” (LSTR). Methodology: A 5-year-old female patient sought dental care complaining of pain in the region of tooth 85 whose oral clinical examination revealed the presence of caries with pulp involvement. In the preoperative period (T1), the patient presented with fistula, abscess and edema. Endodontic treatment was performed using the LSTR technique with triple antibiotic paste. In the follow-up, due to radiographic aspects, a large interradicular lesion was observed in T1 and at the end of the follow-up (T4 / T5), complete bone regeneration was observed in the region. Conclusion: Due to the high antibacterial efficacy of the paste used, the LSTR technique showed satisfactory results in the pulpectomy of a deciduous necrotic molar. Clinical significance: This technique shows the potential to be used in cases to being performed in a shorter operative time, which can be useful in the treatment of children with negative behavior.

Periodontal Bifunctional Biomaterials: Progress and Perspectives.

Periodontitis is a chronic infectious disease that destroys periodontal supportive tissues and eventually causes tooth loss. It is attributed to microbial and immune factors. The goal of periodontal therapy is to achieve complete alveolar bone regeneration while keeping inflammation well-controlled. To reach this goal, many single or composite biomaterials that produce antibacterial and osteogenic effects on periodontal tissues have been developed, which are called bifunctional biomaterials. In this review, we summarize recent progress in periodontal bifunctional biomaterials including bioactive agents, guided tissue regeneration/guided bone regeneration (GTR/GBR) membranes, tissue engineering scaffolds and drug delivery systems and provide novel perspectives. In conclusion, composite biomaterials have been greatly developed and they should be chosen with care due to the risk of selection bias and the lack of evaluation of the validity of the included studies.

Preserving the vitality of teeth adjacent to a large radicular cyst in periapical microsurgery: a case report with 4-year follow-up

BackgroundRadicular cysts may enlarge considerably, cause extensive bone destruction, and jeopardize the integrity of the associated vital teeth. The different treatment approaches are aimed mainly at eliminating the cystic epithelial membrane while reducing the risk of injury to vital structures. Contrary to other treatment modalities, preapical surgery offers an unequivocal single occasion resolution for the patient. However, it has been associated with higher risk of collateral damages.Case presentationA patient presented with a large radicular cyst originating from a maxillary lateral incisor. The adjacent central and canine teeth initially failed to exhibit responses to sensibility tests but showed signs of vitality. Microsurgical management was aimed at enucleating the cystic membrane while maintaining adjacent teeth vitality. Upon careful and controlled cyst enucleation under the dental operating microscope, the neurovascular bundle of one of the involved teeth was visualized and its integrity was maintained throughout the procedure.ResultsThe procedure was successful and follow up recalls revealed recovery of normal sensibility of tooth 11 and 13 with complete bone regeneration around their apices.ConclusionWithin the limitation of the present case report, we demonstrated that complete excision of large periapical cyst can be performed without sacrificing the vitality of the adjacent teeth, by preserving the integrity of their neurovascular supply through controlled microsurgical enucleation, and by a potential apical vascular repair ensuing unintended injury. Diagnosing the pulp vitality of non-offending teeth whose apices protrude into the cystic lumen is a complex process and can be misleading. Pressure from the growing cyst can inhibit vital teeth responses to neural-based sensibility tests leading to false negative results. Thus, in such cases, the use of blood perfusion-based vitality testing is recommended for correct initial diagnosis.

Osteochondral Tissue Engineering: The Potential of Electrospinning and Additive Manufacturing.

The socioeconomic impact of osteochondral (OC) damage has been increasing steadily over time in the global population, and the promise of tissue engineering in generating biomimetic tissues replicating the physiological OC environment and architecture has been falling short of its projected potential. The most recent advances in OC tissue engineering are summarised in this work, with a focus on electrospun and 3D printed biomaterials combined with stem cells and biochemical stimuli, to identify what is causing this pitfall between the bench and the patients’ bedside. Even though significant progress has been achieved in electrospinning, 3D-(bio)printing, and induced pluripotent stem cell (iPSC) technologies, it is still challenging to artificially emulate the OC interface and achieve complete regeneration of bone and cartilage tissues. Their intricate architecture and the need for tight spatiotemporal control of cellular and biochemical cues hinder the attainment of long-term functional integration of tissue-engineered constructs. Moreover, this complexity and the high variability in experimental conditions used in different studies undermine the scalability and reproducibility of prospective regenerative medicine solutions. It is clear that further development of standardised, integrative, and economically viable methods regarding scaffold production, cell selection, and additional biochemical and biomechanical stimulation is likely to be the key to accelerate the clinical translation and fill the gap in OC treatment.

Additively Manufactured Absorbable Porous Metal Implants – Processing, Alloying and Corrosion Behavior

Treating large bone defects is still a clinical challenge without perfect solution, mainly due to the unavailability of suitable bone implants. Additively manufactured (AM) absorbable porous metals provide unparalleled opportunities to realize the challenging requirements for bone-mimetic implants. Firstly, multi-scale geometries of such implants can be customized to mimic the micro-architecture and mechanical properties of human bone. The interconnected porous structure additionally increases the surface area to facilitate adhesion and proliferation of bone cells. Finally, their absorption properties are tunable to maintain the structural integrity of the implant throughout the bone healing process, ensuring sufficient loadbearing when needed and full disintegration after their job is done. Such a combination of properties paves the way for complete bone regeneration and remodeling. It is important to thoroughly characterize the biodegradation behavior, mechanical properties, and bone regeneration ability when developing ideal porous absorbable metal implants. We review the state-of-the-art of absorbable porous metals manufactured by selective laser melting (SLM), with a focus on geometrical design, material type, processing, and post-treatment. The impact of the latter aspects on absorption behavior, resulting mechanical properties, and cytocompatibility will also be briefly discussed. In comparison to their solid inert counterparts, AM absorbable porous metals (APMs) have shown many unique properties and hold tremendous potential to further optimize their application-specific performance due to their flexible geometrical design. We further highlight challenges in adopting AM APMs for future Orthopedic solutions.

Fabrication and Usage of a Nanocomposite Scaffold in Segmental Bone Healing: An Animal Model Study

Objective- The loss of bone fragments, often due to trauma, infection, mass loss, or even complete bone regeneration after complicated fractures, is one of the constant challenges in medicine and veterinary medicine. The aim of this study was to fabricate and use a nanocomposite scaffold in segmental bone healing in rabbits.Design- Experimental StudyAnimals- Forty adult male New Zealand male rabbitsProcedures- The animals were randomly divided into four groups of 10 animals each. On femur of each rabbit a bilateral 6 mm diameter defect was created. In the first group (control), no substance was used, in the second group, hydroxyapatite, in the third group, nanocomposite tri-calcium phosphate (TCP) and in fourth group, autograft was used to fill the defect. Bone specimens were harvested for histopathological evaluations on days 15 and 60 for evaluation of four indices of union, spongiosa, cortex and bone marrow. Results- The results of using nanocomposite tricalcium phosphate in comparison with other groups were significantly different in all cases. Conclusion and Clinical Relevance- It could be admitted that nanocomposite tri-calcium phosphate scaffold had a positive effect on the healing process and showed satisfactory bone strength, therefore, it could be widely used in orthopedic surgery as well as tissue engineering.

Donorsite defect of medial femoral condyle corticoperiostal flap in the treatment of lower limb infected nonunions.

Chronic osteomyelitis is a major challenge in orthopaedic surgery; it is the result of open fracture, periprosthetic infection and septic arthritis. Osteomyelitis leads to fracture nonunion. The treatment of bone infection and infected nonunion consists primarily of the complete removal of infected and avascular bone and soft tissue from the surgical site, followed by local and systemic pathogen-specific antibiotic therapy and temporary stabilisation, but may lead to massive skeletal and soft tissue defects. The use of free or pedicled vascularised bone transfers and callus distraction techniques (bone transport) has been recommended for large bone defects. The aim of this study is to evaluate the results of patients affected by infected non-unions of the lower limbs, treated with a corticoperiosteal flap from the medial femoral condyle and to investigate the donor site morbidity of this flap. The patients were 11 males (average age of 45.6 years), who presented a nonunion of the tibial diaphysis in 7 cases and non-union of femoral diaphysis in 4 cases, treated with free or pedicled corticoperiosteal flap. In all patients, surgical debridement was performed before the flap of infected bone and soft tissues that would not contribute to wound healing. Clinical and radiographic evaluations of the recipient site were performed. Preoperative and postoperative X-ray and MRI scans after the 3-year follow-up of the donor site were performed, in order to observe possible bone restoration and any complications. The patients reported complete clinical and radiographic bone healing in 90.9 % of cases. As regards donor site, there were no differences between the medial femoral donor condyle compared to the contralateral site, due to complete regeneration of donor site bone. MRI investigation showed complete restoration of the donor site with vascularised bone in all patients. Our results suggest that the use of bone flaps for the treatment of infected non-unions is an effective procedure, that must be performed after accurate debridement of the non-union site. The corticoperiosteal flap seems to have few morbidities on the donor site and a high percentage of successful bone healing.

Antibacterial, anti-biofilm and angiogenic calcium sulfate-nano MgO composite bone void fillers for inhibiting Staphylococcus aureus infections

Antibiotic loaded calcium sulfate (CS) beads are widely reported to be used as bone void fillers. Application of these beads has been found effective in the inhibition of bacterial infections and enhanced bone regeneration, though lacking the ability to enhance angiogenesis. Thus, realizing the importance of angiogenesis for complete bone regeneration, magnesium oxide nanoparticles (MgO Nps) of ≤50 nm and tigecycline (Tg) incorporated CS based nanocomposite (Tg-NC) (Tigecycline-Nanocomposite) beads were prepared. N, O-carboxymethyl chitosan solution was chosen as a binder in the preparation of CS-based beads for the enhanced stability. The prepared Tg-NC beads were characterized using SEM, EDS and FTIR. The Tg-NC beads were cytocompatible showing pro-angiogenic property. The sustained drug release for 10 days from Tg-NC beads was found to be very effective in the inhibition of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). Also, Tg-NC beads effectively inhibited biofilms exhibited by Staphylococcus aureus. Thus prepared Tg-NC beads can be used as bone void fillers for inhibiting infections and promoting angiogenesis.

Mineralized Hydrogels Induce Bone Regeneration in Critical Size Cranial Defects.

Sequential mineralization enables the integration of minerals within the 3D structure of hydrogels. Hydrolyzed collagen-based hydrogels are sequentially mineralized over 10 cycles. One cycle is defined as an incubation period in calcium chloride dihydrate followed by incubation in sodium phosphate dibasic dihydrate. Separate cycles are completed at 30-minute and 24-hour intervals. For the gels mineralized for 30min and 24 h, the compressive moduli increases from 4.25 to 87.57kPa and from 4.25 to 125.47kPa, respectively, as the cycle number increases from 0 to 10. As indicated by X-ray diffraction (XRD) and Fourier transform infrared analysis (FTIR) analyses, the minerals in the scaffolds are mainly hydroxyapatite. In vitro experiments, which measure mechanical properties, porous structure, mineral content, and gene expression are performed to evaluate the physical properties and osteoinductivity of the scaffolds. Real time-quantitative polymerase chain reaction (RT-qPCR) demonstrates 4-10 fold increase in the expression of BMP-7 and osteocalcin. The in vivo subcutaneous implantation demonstrates that the scaffolds are biocompatible and 90% biodegradable. The critical size cranial defects in vivo exhibit nearly complete bone regeneration. Cycle 10 hydrogels mineralized for 24 h have a volume of 59.86 mm3 and a density of 1946.45 HU. These results demonstrate the suitability of sequentially mineralized hydrogel scaffolds for bone repair and regeneration.

An engineered cell-laden adhesive hydrogel promotes craniofacial bone tissue regeneration in rats.

Cell-laden hydrogels are widely used in tissue engineering and regenerative medicine. However, many of these hydrogels are not optimized for use in the oral environment, where they are exposed to blood and saliva. To address these challenges, we engineered an alginate-based adhesive, photocrosslinkable, and osteoconductive hydrogel biomaterial (AdhHG) with tunable mechanical properties. The engineered hydrogel was used as an injectable mesenchymal stem cell (MSC) delivery vehicle for craniofacial bone tissue engineering applications. Subcutaneous implantation in mice confirmed the biodegradability, biocompatibility, and osteoconductivity of the hydrogel. In a well-established rat peri-implantitis model, application of the adhesive hydrogel encapsulating gingival mesenchymal stem cells (GMSCs) resulted in complete bone regeneration around ailing dental implants with peri-implant bone loss. Together, we have developed a distinct bioinspired adhesive hydrogel with tunable mechanical properties and biodegradability that effectively delivers patient-derived dental-derived MSCs. The hydrogel is photocrosslinkable and, due to the presence of MSC aggregates and hydroxyapatite microparticles, promotes bone regeneration for craniofacial tissue engineering applications.