Nerve Growth Factor-Preconditioned Mesenchymal Stem Cell-Derived Exosome-Functionalized 3D-Printed Hierarchical Porous Scaffolds with Neuro-Promotive Properties for Enhancing Innervated Bone Regeneration.

The essential role of the neural network in enhancing bone regeneration has often been overlooked in biomaterial design, leading to delayed or compromised bone healing. Engineered mesenchymal stem cells (MSCs)-derived exosomes are becoming increasingly recognized as potent cell-free agents for manipulating cellular behavior and improving therapeutic effectiveness. Herein, MSCs are stimulated with nerve growth factor (NGF) to regulate exosomal cargoes to improve neuro-promotive potential and facilitate innervated bone regeneration. In vitro cell experiments showed that the NGF-stimulated MSCs-derived exosomes (N-Exos) obviously improved the cellular function and neurotrophic effects of the neural cells, and consequently, the osteogenic potential of the osteo-reparative cells. Bioinformatic analysis by miRNA sequencing and pathway enrichment revealed that the beneficial effects of N-Exos may partly be ascribed to the NGF-elicited multicomponent exosomal miRNAs and the subsequent regulation and activation of the MAPK and PI3K-Akt signaling pathways. On this basis, N-Exos were delivered on the micropores of the 3D-printed hierarchical porous scaffold to accomplish the sustained release profile and extended bioavailability. In a rat model with a distal femoral defect, the N-Exos-functionalized hierarchical porous scaffold significantly induced neurovascular structure formation and innervated bone regeneration. This study provided a feasible strategy to modulate the functional cargoes of MSCs-derived exosomes to acquire desirable neuro-promotive and osteogenic potential. Furthermore, the developed N-Exos-functionalized hierarchical porous scaffold may represent a promising neurovascular-promotive bone reparative scaffold for clinical translation.

[Research of implant accuracy using a digital registration method].

PURPOSE: The aim of this study was to introduce a new method to evaluate the clinical accuracy of implant position. The results were compared to traditional cone beam CT (CBCT) method. METHODS: A total of 36 implants from 24 patients with sufficient bone volume were enrolled into the study. CBCT method and digital registration method were compared to evaluate the accuracy of implant position. The measurement parameters were defined as deviations between ideal and postsurgical implant position at occlusal point(d1), apical point(d2) and axis(α). The deviations between two methods were analyzed with SPSS 19.0 software package. RESULTS: The deviations between ideal and postsurgical implant position using CBCT were (0.88±0.64) mm for occlusal point, (1.07±0.85) mm for apical point and (4.74±2.35)° for angle. In digital registration method, the deviations were (0.86±0.67) mm for occlusal point, (1.12±0.88) mm for apical point and (4.56±2.66)° for angle. No significant difference(P＞0.05) was found between the two methods. CONCLUSIONS: There was no significant difference between the two methods in evaluating the clinical accuracy of implant position. Digital registration method could be accepted in clinical application.

Electreted Sandwich Membranes with Persistent Electrical Stimulation for Enhanced Bone Regeneration.

Physiologically relevant electrical microenvironments play an indispensable role in manipulating bone metabolism. Although implanted biomaterials that simulate the electrical properties of natural tissues using conductive or piezoelectric materials have been introduced in the field of bone regeneration, the application of electret materials to provide stable and persistent electrical stimulation has rarely been studied in biomaterial design. In this study, a silicon dioxide electret-incorporated poly(dimethylsiloxane) (SiO2/PDMS) composite electroactive membrane was designed and fabricated to explore its bone regeneration efficacy. SiO2 electrets were homogeneously dispersed in the PDMS matrix, and sandwich-like composite membranes were fabricated using a facile layer-by-layer blade-coating method. Following the encapsulation, electret polarization was conducted to obtain the electreted composite membranes. The surface potential of the composite membrane could be adjusted to a bone-promotive biopotential by tuning the electret concentration, and the prepared membranes exhibited favorable electrical stability during an observation period of up to 42 days. In vitro biological experiments indicated that the electreted SiO2/PDMS membrane promoted cellular activity and osteogenic differentiation of mesenchymal stem cells. In vivo, the electreted composite membrane remarkably facilitated bone regeneration through persistent endogenous electrical stimulation. These findings suggest that the electreted sandwich-like membranes, which maintain a stable and physiological electrical microenvironment, are promising candidates for enhancing bone regeneration.

Effect of Pore Size on Cell Behavior Using Melt Electrowritten Scaffolds.

Tissue engineering technology has made major advances with respect to the repair of injured tissues, for which scaffolds and cells are key factors. However, there are still some issues with respect to the relationship between scaffold and cell growth parameters, especially that between the pore size and cells. In this study, we prepared scaffolds with different pore sizes by melt electrowritten (MEW) and used bone marrow mensenchymal stem cells (BMSCs), chondrocytes (CCs), and tendon stem cells (TCs) to study the effect of the scaffold pore size on cell adhesion, proliferation, and differentiation. It was evident that different cells demonstrated different adhesion and proliferation rates on the scaffold. Furthermore, different cell types showed differential preferences for scaffold pore sizes, as evidenced by variations in cell viability. The pore size also affected the differentiation and gene expression pattern of cells. Among the tested cells, BMSCs exhibited the greatest viability on the 200-µm-pore-size scaffold, CCs on the 200- and 100-µm scaffold, and TCs on the 300-µm scaffold. The scaffolds with 100- and 200-µm pore sizes induced a significantly higher proliferation, chondrogenic gene expression, and cartilage-like matrix deposition after in vitro culture relative to the scaffolds with smaller or large pore sizes (especially 50 and 400 µm). Taken together, these results show that the architecture of 10 layers of MEW scaffolds for different tissues should be different and that the pore size is critical for the development of advanced tissue engineering strategies for tissue repair.

A host-coupling bio-nanogenerator for electrically stimulated osteogenesis.

Implantable self-powered generators (ISPGs) have been extensively explored as energy supplies for driving electronics and electrically stimulated therapeutics in vivo. However, some drawbacks arise, such as complicated architectonics, inescapability of wire connection, energy instability, and consumption. In this study, a host-coupling bio-nanogenerator (HCBG) is developed to configure a self-powered regional electrical environment for powerful bone regeneration. An HCBG consists of a porous electret nanofiber mat coupled with interstitial fluid and stimulated objects of the host after implantation, forming a host coupling effect. This bio-nanogenerator not only overcomes the disadvantages of general ISPGs, but also accomplishes both biomechanical energy scavenging and electrical stimulation therapeutics. The enhancement of osteogenesis differentiation of bone marrow mesenchymal stem cells in vitro and bone regeneration in vivo are remarkably achieved. Moreover, osteogenic ability is systematically evaluated by regulating the electrical performance of HCBGs. Osteogenic differentiation is activated by upregulating more cytosolic calcium ion, following to activate the calcium ion-induced osteogenic signal pathway, while applying electrical stimulation. As an implantable medical technology, the HCBG provides an explorative insight to facilitate the development of ISPG-based electrical medical therapeutics.

A low-temperature-printed hierarchical porous sponge-like scaffold that promotes cell-material interaction and modulates paracrine activity of MSCs for vascularized bone regeneration.

Mesenchymal stem cells (MSCs) secrete paracrine trophic factors that are beneficial for tissue regeneration. In this study, a sponge-like scaffold with hierarchical and interconnected pores was developed using low-temperature deposition modeling (LDM) printing. Its effects on the cellular behavior, especially on the paracrine secretion patterns of MSCs, were comprehensively investigated. We found that compared with the scaffolds printed via the fused deposition modeling (FDM) technique, the LDM-printed sponges enhanced the adhesion, retention, survival, and ingrowth of MSCs and promoted cell-material interactions. Moreover, the paracrine functions of the cultured MSCs on the LDM-printed sponges were improved, with significant secretion of upregulated immunomodulatory, angiogenic, and osteogenic factors. MSCs on the LDM-printed sponges exert beneficial paracrine effects on multiple regenerative processes, including macrophage polarization, tube formation, and osteogenesis, verifying the enhanced immunomodulatory, angiogenic, and osteogenic potential. Further protein function assays indicated that focal adhesion kinase (FAK), downstream AKT, and yes-associated-protein (YAP) signaling might participate in the required mechanotransductive pathways, through which the hierarchical porous structures stimulated the paracrine effects of MSCs. In a rat distal femoral defect model, the MSC-laden LDM-printed sponges significantly promoted vascularized bone regeneration. The results of the present study demonstrate that the hierarchical porous biomimetic sponges prepared via LDM printing have potential applications in tissue engineering based on their cell-material interaction promotion and MSC paracrine function modulation effects. Furthermore, our findings suggest that the optimization of biomaterial properties to direct the paracrine signaling of MSCs would enhance tissue regeneration.

High-precision, gelatin-based, hybrid, bilayer scaffolds using melt electro-writing to repair cartilage injury.

Articular cartilage injury is a common disease in the field of orthopedics. Because cartilage has poor self-repairing ability, medical intervention is needed. Using melt electro-writing (MEW) technology, tissue engineering scaffolds with high porosity and high precision can be prepared. However, ordinary materials, especially natural polymer materials, are difficult to print. In this study, gelatin was mixed with poly (lactic-co-glycolic acid) to prepare high-concentration and high-viscosity printer ink, which had good printability and formability. A composite scaffold with full-layer TGF-ß1 loading mixed with hydroxyapatite was prepared, and the scaffold was implanted at the cartilage injury site; microfracture surgery was conducted to induce the mesenchyme in the bone marrow. Quality stem cells thereby promoted the repair of damaged cartilage. In summary, this study developed a novel printing method, explored the molding conditions based on MEW printing ink, and constructed a bioactive cartilage repair scaffold. The scaffold can use autologous bone marrow mesenchymal stem cells and induce their differentiation to promote cartilage repair.

Hydroxyapatite-Bovine Serum Albumin-Paclitaxel Nanoparticles for Locoregional Treatment of Osteosarcoma.

Osteosarcoma is the most primary type of bone tumor occurring in the pediatric and adolescent age groups. In order to obtain the most appropriate prognosis, both tumor recurrence inhibition and bone repair promotion are required. In this study, a ternary nanoscale biomaterial/antitumor drug complex including hydroxyapatite (HA), bovine serum albumin (BSA) and paclitaxel (PTX) is prepared for post-surgical cancer treatment of osteosarcoma in situ. The HA-BSA-PTX nanoparticles, about 55 nm in diameter with drug loading efficiency (32.17 wt%), have sustained release properties of PTX and calcium ions (Ca2+ ) and low cytotoxicity to human fetal osteoblastic (hFOB 1.19) cells in vitro. However, for osteosarcoma (143B) cells, the proliferation, migration, and invasion ability are significantly inhibited. The in situ osteosarcoma model studies demonstrate that HA-BSA-PTX nanoparticles have significant anticancer effects and can effectively inhibit tumor metastasis. Meanwhile, the detection of alkaline phosphatase activity, calcium deposition, and reverse transcription-polymerase chain reaction proves that the HA-BSA-PTX nanoparticles can promote the osteogenic differentiation. Therefore, the HA-BSA-PTX nanodrug delivery system combined with sustained drug release, antitumor, and osteogenesis effects is a promising agent for osteosarcoma adjuvant therapy.

A 3D-Bioprinted dual growth factor-releasing intervertebral disc scaffold induces nucleus pulposus and annulus fibrosus reconstruction.

Regeneration of Intervertebral disc (IVD) is a scientific challenge because of the complex structure and composition of tissue, as well as the difficulty in achieving bionic function. Here, an anatomically correct IVD scaffold composed of biomaterials, cells, and growth factors were fabricated via three-dimensional (3D) bioprinting technology. Connective tissue growth factor (CTGF) and transforming growth factor-ß3 (TGF-ß3) were loaded onto polydopamine nanoparticles, which were mixed with bone marrow mesenchymal stem cells (BMSCs) for regenerating and simulating the structure and function of the nucleus pulposus and annular fibrosus. In vitro experiments confirmed that CTGF and TGF-ß3 could be released from the IVD scaffold in a spatially controlled manner, and induced the corresponding BMSCs to differentiate into nucleus pulposus like cells and annulus fibrosus like cells. Next, the fabricated IVD scaffold was implanted into the dorsum subcutaneous of nude mice. The reconstructed IVD exhibited a zone-specific matrix that displayed the corresponding histological and immunological phenotypes: primarily type II collagen and glycosaminoglycan in the core zone, and type I collagen in the surrounding zone. The testing results demonstrated that it exhibited good biomechanical function of the reconstructed IVD. The results presented herein reveal the clinical application potential of the dual growth factors-releasing IVD scaffold fabricated via 3D bioprinting. However, the evaluation in large mammal animal models needs to be further studied.

Bioinspired stratified electrowritten fiber-reinforced hydrogel constructs with layer-specific induction capacity for functional osteochondral regeneration.

Despite significant advances in osteochondral tissue engineering, it remains challenging to successfully reconstruct native-like complex tissues organized in three-dimension with spatially varying compositional, structural and functional properties. In this contribution, inspired by the gradients in extracellular matrix (ECM) composition and collagen fiber architecture in native osteochondral tissue, we designed and fabricated a tri-layered (superficial cartilage (S), deep cartilage (D) and subchondral bone (B) layer) stratified scaffold in which a mesenchymal stem cell (MSC)-laden gelatin methacrylamide (GelMA) hydrogel with zone-specific growth factor delivery was combined with melt electrowritten triblock polymer of poly(ε-caprolactone) and poly(ethylene glycol) (PCEC) networks with depth-dependent fiber organization. Introducing PCEC fibers into the weak GelMA hydrogel contributed to a significant increase in mechanical strength. In vitro biological experiments indicated that the stratified fiber-reinforced and growth factor-loaded hydrogel construct induced the MSCs to differentiate down both the chondrogenic and osteogenic lineages and that the engineered complex exhibited cellular phenotype and matrix accumulation profiles resembling those of the native tissue. Simultaneous cartilage and subchondral bone regeneration were achieved in vivo by using the tri-layered integrated scaffold. More importantly, the inclusion of the S layer could impart the regenerated cartilage with a more lubricating and wear-resistant surface. These findings suggest that the bioinspired construct mimicking the spatial variations of native osteochondral tissue might serve as a promising candidate to enhance osteochondral regeneration.

Preparation of high precision multilayer scaffolds based on Melt Electro-Writing to repair cartilage injury.

Rationale: Articular cartilage injury is quite common. However, post-injury cartilage repair is challenging and often requires medical intervention, which can be aided by 3D printed tissue engineering scaffolds. Specifically, the high accuracy of Melt Electro-Writing (MEW) technology facilitates the printing of scaffolds that imitate the structure and composition of natural cartilage to promote repair. Methods: MEW and Inkjet printing technology was employed to manufacture a composite scaffold that was then implanted into a cartilage injury site through microfracture surgery. While printing polycaprolactone (PCL) or PCL/hydroxyapatite (HA) scaffolds, cytokine-containing microspheres were sprayed alternately to form multiple layers containing transforming growth factor-ß1 and bone morphogenetic protein-7 (surface layer), insulin-like growth factor-1 (middle layer), and HA (deep layer). Results: The composite biological scaffold was conducive to adhesion, proliferation, and differentiation of mesenchymal stem cells recruited from the bone marrow and blood. Meanwhile, the environmental differences between the scaffold's layers contributed to the regional heterogeneity of chondrocytes and secreted proteins to promote functional cartilage regeneration. The biological effect of the composite scaffold was validated both in vitro and in vivo. Conclusion: A cartilage repair scaffold was established with high precision as well as promising mechanical and biological properties. This scaffold can promote the repair of cartilage injury by using, and inducing the differentiation and expression of, autologous bone marrow mesenchymal stem cells.

A multifunctional electrowritten bi-layered scaffold for guided bone regeneration.

The guided bone regeneration (GBR) concept has been extensively utilized to treat maxillofacial bone defects in clinical practice. However, the repair efficacy of currently available GBR membranes is often compromised by their limited bone regeneration potential and deficient antibacterial activity. In this study, inspired by the bi-layered structure design of the commonly used Bio-GideⓇmembrane, we designed and fabricated a new kind of multifunctional bi-layered "GBR scaffold" combining solution electrospinning writing (SEW) and solution electrospinning (SES) techniques using a single SEW printer. Copper-loaded mesoporous silica nanoparticles (Cu@MSNs) were incorporated into the poly(lactic-co-glycolic acid)/gelatin (PLGA/Gel, denoted as PG) fiber matrix to construct a composite PG-Cu@MSNs fibrous scaffold. The obtained GBR scaffold consisted of a loose and porous SEW layer to support and facilitate bone ingrowth, and a dense and compact SES layer to resist non-osteoblast interference. The resulting enhanced mechanical properties, coordinated degradation profile, and facile preparation procedure imparted the composite scaffold with good clinical feasibility. In vitro biological experiments indicate that the PG-Cu@MSNs composite scaffold exhibited favorable osteogenic and antibacterial properties. Furthermore, an in vivo rat periodontal defect model further confirmed the promising bone regeneration efficacy of the PG-Cu@MSNs scaffold. In conclusion, the developed electrowritten Cu@MSNs-incorporated bi-layered scaffold with hierarchical architecture and concurrent osteogenic and antibacterial functions may hold great potential for application in GBR.

Stud vs Bar Attachments for Maxillary Four-Implant-Supported Overdentures: 3- to 9-year Results from a Retrospective Study.

PURPOSE: The aim of this study was to compare the clinical outcomes of four-implant-supported overdentures retained by stud or bar attachments for patients with an edentulous maxilla. MATERIALS AND METHODS: From January 2008 to December 2014, patients with maxillary edentulism were enrolled in this retrospective study. The insertion of four maxillary dental implants was followed by restoration with either stud-retained or bar-retained overdentures. The characteristics of the subjects and implants were recorded. Implant survival rates, marginal bone loss, peri-implant clinical parameters, and prosthetic maintenance efforts were evaluated at the last follow-up time. Furthermore, patients were asked to complete a satisfaction questionnaire using a modified Denture Satisfaction scale at their last follow-up visit. The data were statistically analyzed, and the level of significance was set at α = .05. RESULTS: A total of 132 implants were placed in 33 patients, of whom 18 were restored with four-implant-supported overdentures retained by stud attachments, and the other 15 with four-implant-supported overdentures retained by bar attachments. Thirty-one patients and 124 implants were available for the entire follow-up. During a mean follow-up period of 77 months (range: 36 to 111 months), five among 72 implants failed for three patients in the stud-retained group and two among 60 implants failed for two patients in the bar-retained group, resulting in estimated cumulative implant survival rates of 81.4% and 86.2% for the stud-retained group and the bar-retained group, respectively. Except for the modified Plaque Index (mPI, P = .035), no significant differences were indicated between the two attachment groups in terms of implant survival rate, marginal bone loss, or peri-implant clinical parameters. Peri-/inter-implant gingival hyperplasia occurred only with implants under bar attachments. Over the entire observation period, the incidence of prosthetic maintenance treatments was 2.12 per patient per study for the stud-retained group and 2.29 per patient per study for the bar-retained group. Patients in both groups reported a high degree of satisfaction. CONCLUSION: Within the limitations of this study, no significant differences were indicated between the clinical outcomes of maxillary four-implant-supported overdentures with either stud or bar attachments, although a higher modified Plaque Index was observed for the bar-retained group. Furthermore, prostheses with stud attachments were advantageous for their convenient cleaning and repair. Patients with compromised systemic and periodontal conditions should be treated with caution. Further clinical studies with larger sample sizes and stricter epidemiologic designs are still needed.

Bi-layered electrospun nanofibrous membrane with osteogenic and antibacterial properties for guided bone regeneration.

Guided bone regeneration (GBR) membranes have the potential to prevent the invasion of epithelial and connective tissues as well as to maintain a stable space for facilitating the ingrowth of regenerative bone tissue. However, the bioactivity and regeneration potential of currently available membranes still need to be improved. In this study, a novel bi-layered membrane with both osteogenic and antibacterial functions was developed for GBR applications. The loose layer (LL) of the membrane was composed of conjugated electrospun poly (lactic-co-glycolic acid) (PLGA)/gelatin nanofibers incorporating dexamethasone-loaded mesoporous silica nanoparticles (DEX@MSNs), while the dense layer (DL) of the membrane consisted of traditionally electrospun PLGA nanofibers loaded with the broad-spectrum antibiotic doxycycline hyclate (DCH). Morphological results showed that the LL (DEX@MSNs/PLGA/Gel) membrane exhibited a porous and loosely packed structure, which was beneficial for cell adhesion and infiltration, while the DL (DCH/PLGA) membrane remained dense enough to act as a barrier. In vitro drug release tests indicated that both DEX and DCH followed a favorable sustained release profile. The cell viability evaluation suggested that the electrospun membranes possessed good cytocompatibility. Furthermore, in vitro osteogenesis analyses demonstrated that the DEX@MSNs/PLGA/Gel composite membrane possessed an enhanced osteoinductive capacity for rat bone marrow stem cells (BMSCs), which was verified by the increased alkaline phosphatase (ALP) activity, the enhanced calcium deposition, and the upregulated osteocalcin (OCN) expression. In vitro antimicrobial experiments revealed the effective antibacterial potency of the DCH/PLGA membrane. In conclusion, the prepared nanocarrier-incorporated bi-layered composite membrane with combined osteogenic and antibacterial properties may be a promising candidate for GBR application.

Novel mutations identified in patients with tooth agenesis by whole-exome sequencing.

OBJECTIVES: To identify potentially pathogenic mutations for tooth agenesis by whole-exome sequencing. SUBJECTS AND METHODS: Ten Chinese families including five families with ectodermal dysplasia (syndromic tooth agenesis) and five families with selective tooth agenesis were included. Whole-exome sequencing was performed using genomic DNA. Potentially pathogenic mutations were identified after data filtering and screening. The pathogenicity of novel variants was investigated by segregation analysis, in silico analysis, and functional studies. RESULTS: One novel mutation (c.441_442insACTCT) and three reported mutations (c.252delT, c.463C>T, and c.1013C>T) in EDA were identified in families with ectodermal dysplasia. The novel EDA mutation was co-segregated with phenotype. A functional study revealed that NF-κB activation was compromised by the identified mutations. The secretion of active EDA was also compromised detection by western blotting. Novel Wnt10A mutations (c.521T>C and c.653T>G) and EVC2 mutation (c.1472C>T) were identified in families with selective tooth agenesis. The Wnt10A c.521T>C mutation and the EVC2 c.1472C>T mutation were considered as pathogenic for affecting highly conserved amino acids, co-segregated with phenotype and predicted to be disease-causing by SIFT and PolyPhen2. Moreover, several reported mutations in PAX9, Wnt10A, and FGFR3 were also detected. CONCLUSIONS: Our study expanded our knowledge on tooth agenesis spectrum by identifying novel variants.

Long-term Schneiderian membrane thickness changes following zygomatic implant placement: A retrospective radiographic analysis using cone beam computed tomography.

OBJECTIVES: The purpose of this retrospective study was to evaluate the long-term changes in the thickness of Schneiderian membranes after zygomatic implant placement using cone beam computed tomography (CBCT). MATERIAL AND METHODS: Twenty-five consecutive patients were included in this study. All the patients underwent bilateral zygomatic implant placement. Schneiderian membrane thickness (SMT) in 49 maxillary sinuses (one sinus was not included because of early loss of the zygomatic implants) was measured using CBCT before and at least 1 year after zygomatic implant placement. Ostium patency of each sinus was also evaluated and recorded. RESULTS: In total, 84 zygomatic implants and 30 regular implants were placed in included patients. Two unilateral maxillary zygomatic implants in one patient were removed 2 months after implant placement. The SMT increased from 1.03 mm (inter-quartile range: 1.57 mm) to 1.33 mm (inter-quartile range: 1.98 mm) after a median follow-up time of 23.00 months (inter-quartile range: 14 months), and the difference was statistically significant. Before zygomatic implant insertion, 24.5% (12/49) of sinuses had SMT greater than 2 mm, whereas this value was 28.6% (14/49) after zygomatic implant placement. The percentage of sinuses observed with ostium patency also increased from 2.0% (1/49) to 12.2% (6/49). CONCLUSIONS: Chronic Schneiderian membrane thickening could result from zygomatic implant insertion. Intensive postoperative care and clinical and radiographic monitoring are recommended after zygomatic implant placement.

Prognosis of Combining Remaining Teeth and Implants in Double-Crown-Retained Removable Dental Prostheses: A Systematic Review and Meta-Analysis.

PURPOSE: The reliability of combining natural teeth and implants in one removable prosthesis is controversial. This systematic review was conducted to evaluate the prognosis of combined tooth/implant-supported double-crown-retained removable dental prostheses (DCR-RDPs) and to compare them with solely implant-supported prostheses with a minimum observation period of 3 years. MATERIALS AND METHODS: Electronic database (PubMed, Embase, Central, and SCI) and manual searches up to August 2016 were conducted to identify human clinical studies on tooth/implant-supported DCR-RDPs. Literature selection and data extraction were accomplished by two independent reviewers. Meta-analyses of survival and complication rates were performed separately for combined tooth/implant-supported and solely implant-supported DCRRDPs. RESULTS: Among the initially identified 366 articles, 17 were included in a quantitative analysis. The estimated overall cumulative survival rate (CSR) for implants in combined tooth/implant-supported DCRRDPs was 98.72% (95% confidence interval [95% CI]: 96.98% to 99.82%), and that for implants in solely implant-supported DCR-RDPs was 98.83% (95% CI: 97.45% to 99.75%). The summary CSR for abutment teeth was 92.96% (95% CI: 85.38% to 98.12%). Double-crown-retained dentures with both abutment types showed high CSRs, most of which were approximately 100%. Regarding prosthetic maintenance treatment, the estimated incidence for patients treated with combined tooth/implant-supported RDPs was 0.164 (95% CI: 0.089 to 0.305) per patient per year (T/P/Y) and that for patients restored with solely implant-supported RDPs was 0.260 (95% CI: 0.149 to 0.454) T/P/Y. Based on four studies with combined tooth/implant-supported DCR-RDPs, no intrusion phenomena were encountered. CONCLUSION: Subject to the limitations of the present review, combining remaining teeth and implants in DCR-RDPs is a reliable and predictable treatment modality for partially edentulous patients. Comparable high survival rates and minor biologic or technical complications are observed for combined tooth/implant-supported and solely implant-supported DCR-RDPs. Due to the heterogeneity of the included studies, the results must be interpreted with caution.