This prospective 3-year follow-up clinical study evaluated the survival and success rates of 3DP/AM titanium dental implants to support single implant-supported restorations. After 3 years of loading, clinical, radiographic, and prosthetic parameters were assessed; the implant survival and the implant-crown success were evaluated. Eighty-two patients (44 males, 38 females; age range 26–67 years) were enrolled in the present study. A total of 110 3DP/AM titanium dental implants (65 maxilla, 45 mandible) were installed: 75 in healed alveolar ridges and 35 in postextraction sockets. The prosthetic restorations included 110 single crowns (SCs). After 3 years of loading, six implants failed, for an overall implant survival rate of 94.5%; among the 104 surviving implant-supported restorations, 6 showed complications and were therefore considered unsuccessful, for an implant-crown success of 94.3%. The mean distance between the implant shoulder and the first visible bone-implant contact was 0.75 mm (±0.32) and 0.89 (±0.45) after 1 and 3 years of loading, respectively. 3DP/AM titanium dental implants seem to represent a successful clinical option for the rehabilitation of single-tooth gaps in both jaws, at least until 3-year period. Further, long-term clinical studies are needed to confirm the present results.

Three-dimensional (3D) printing is a valuable tool in the production of complexes structures with specific shapes for tissue engineering. Differently from native tissues, the printed structures are static and do not transform their shape in response to different environment changes. Stimuli-responsive biocompatible materials have emerged in the biomedical field due to the ability of responding to other stimuli (physical, chemical, and/or biological), resulting in microstructures modifications. Four-dimensional (4D) printing arises as a new technology that implements dynamic improvements in printed structures using smart materials (stimuli-responsive materials) and/or cells. These dynamic scaffolds enable engineered tissues to undergo morphological changes in a pre-planned way. Stimuli-responsive polymeric hydrogels are the most promising material for 4D bio-fabrication because they produce a biocompatible and bioresorbable 3D shape environment similar to the extracellular matrix and allow deposition of cells on the scaffold surface as well as in the inside. Subsequently, this review presents different bioresorbable advanced polymers and discusses its use in 4D printing for tissue engineering applications.

Resorbable synthetic and natural polymer-based membranes have been extensively studied for guided tissue regeneration. Alloplastic biomaterials are often used for tissue regeneration due to their lower immunoreactivity when compared with allogeneic and xenogeneic materials. Plenum^® Guide is a synthetic membrane material based on polydioxanone (PDO), whose surface morphology closely mimics the extracellular matrix. In this study, Plenum^® Guide was compared with collagen membranes as a barrier material for bone-tissue regeneration in terms of acute and subchronic systemic toxicity. Moreover, characterizations such as morphology, thermal analysis (Tm = 107.35 °C and crystallinity degree = 52.86 ± 2.97 %, final product), swelling (thickness: 0.25 mm ≅ 436% and 0.5 mm ≅ 425% within 24 h), and mechanical tests (E = 30.1 ± 6.25 MPa; σ = 3.92 ± 0.28 MPa; ε = 287.96 ± 34.68%, final product) were performed. The in vivo results revealed that the PDO membranes induced a slightly higher quantity of newly formed bone tissue than the control group (score: treated group = 15, control group = 13) without detectable systemic toxicity (clinical signs and evaluation of the membranes after necropsy did not result in differences between groups, i.e., non-reaction -> tissue-reaction index = 1.3), showing that these synthetic membranes have the essential characteristics for an effective tissue regeneration. Human adipose-derived stem cells (hASCs) were seeded on PDO membranes; results demonstrated efficient cell migration, adhesion, spread, and proliferation, such that there was a slightly better hASC osteogenic differentiation on PDO than on collagen membranes. Hence, Plenum^® Guide membranes are a safe and efficient alternative for resorbable membranes for tissue regeneration.

Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues using different methods. Active research have confirmed that the most accessible site to collect them is the adipose tissue; which has a significantly higher concentration of MSCs. Moreover; harvesting from adipose tissue is less invasive; there are no ethical limitations and a lower risk of severe complications. These adipose-derived stem cells (ASCs) are also able to increase at higher rates and showing telomerase activity, which acts by maintaining the DNA stability during cell divisions. Adipose-derived stem cells secret molecules that show important function in other cells vitality and mechanisms associated with the immune system, central nervous system, the heart and several muscles. They release cytokines involved in pro/anti-inflammatory, angiogenic and hematopoietic processes. Adipose-derived stem cells also have immunosuppressive properties and have been reported to be “immune privileged” since they show negative or low expression of human leukocyte antigens. Translational medicine and basic research projects can take advantage of bioprinting. This technology allows precise control for both scaffolds and cells. The properties of cell adhesion, migration, maturation, proliferation, mimicry of cell microenvironment, and differentiation should be promoted by the printed biomaterial used in tissue engineering. Self-renewal and potency are presented by MSCs, which implies in an open-source for 3D bioprinting and regenerative medicine. Considering these features and necessities, ASCs can be applied in the designing of tissue engineering products. Understanding the heterogeneity of ASCs and optimizing their properties can contribute to making the best therapeutic use of these cells and opening new paths to make tissue engineering even more useful.

This study evaluated the bioactivity of 3D-printed β-tricalcium phosphate (β-TCP) scaffolds or hydroxyapatite (HA) scaffolds associated with polydioxanone (PDO) membrane (Plenum^® Guide) for guided bone regeneration in rats. Fifty-four rats were divided into three groups (n = 18 animals): autogenous bone + PDO membrane (Auto/PG); 3D-printed β-TCP + PDO membrane (TCP/PG); and 3D-printed HA + PDO membrane (HA/PG). A surgical defect in the parietal bone was made and filled with the respective scaffolds and PDO membrane. The animals were euthanized 7, 30, and 60 days after the surgical procedure for micro-CT, histomorphometric, and immunolabeling analyses. Micro-CT showed an increase in trabecular thickness and a decrease in trabecular separation, even with similar bone volume percentages between TCP/PG and HA/PG vs. Auto/PG. Histometric analysis showed increased bone formation at 30 days in the groups compared to 7 days postoperatively. Immunolabeling analysis showed an increase in proteins related to bone formation at 30 days, and both groups showed a similar immunolabeling pattern. This study concludes that 3D-printed scaffolds associated with PDO membrane (Plenum^® Guide) present similar results to autogenous bone for bone regeneration.

Treatment of complex craniofacial deformities is still a challenge for medicine and dentistry because few approach therapies are available on the market that allow rehabilitation using 3D-printed medical devices. Thus, this study aims to create a scaffold with a morphology that simulates bone tissue, able to create a favorable environment for the development and differentiation of osteogenic cells. Moreover, its association with Plenum Guide, through cell-based tissue engineering (ASCs) for guided bone regeneration in critical rat calvarial defects. The manufacturing and characterization of 3D-printed β-TCP scaffolds for experimental surgery was performed. Nine male rats were divided into three groups: β-TCP + PDO membrane (TCP/PG), β-TCP/ASCs + PDO membrane (TCPasc/PG), and β-TCP/ASCs + PDO membrane/ASCs (TCPasc/PGasc). A surgical defect with a 5-mm diameter was performed in the right parietal bone, and the defect was filled with the 3D-printed β-TCP scaffold and PDO membrane with or without ASCs. The animals were euthanized 7, 14, and 30 days after the surgical procedure for histomorphometric and immunolabeling analyses. 3D-printed β-TCP scaffolds were created with a 404 ± 0.0238 μm gyroid macro-pore and, the association to cell-based therapy promotes, especially in the TCPasc/PGasc group, a bone area formation at the defect border region and the center of the defect. The use of 3D-printed β-TCP scaffolds and PDO membranes associated with cell-based therapy could improve and accelerate guided bone regeneration, promoting an increase in osteogenic capacity and reducing the time involved in the bone formation process. Moreover, using ASCs optimized the bioceramics by increasing its osteoinductive and osteoprogenitor capacity and, even with the resorption of the printed scaffold, aided as a scaffold for mesenchymal cell differentiation, as well as in bone tissue formation.