Alveolar bone regeneration using a 3D-printed patient-specific resorbable scaffold for dental implant placement: A case report.

BACKGROUND: This case report demonstrates the effective clinical application of a 3D-printed, patient-specific polycaprolactone (PCL) resorbable scaffold for staged alveolar bone augmentation. OBJECTIVE: To evaluate the effectiveness of a 3D-printed PCL scaffold in facilitating alveolar bone regeneration and subsequent dental implant placement. MATERIALS AND METHODS: A 46-year-old man with a missing tooth (11) underwent staged alveolar bone augmentation using a patient-specific PCL scaffold. Volumetric bone gain and implant stability were assessed. Histological analysis was conducted to evaluate new bone formation and graft integration. RESULTS: The novel approach resulted in a volumetric bone gain of 364.69 ± 2.53 mm3, sufficient to reconstruct the original alveolar bone contour and permit dental implant placement. Histological analysis showed new bone presence and successful graft integration across all defect zones (coronal, medial, and apical), with continuous new bone formation around and between graft particles. The dental implant achieved primary stability at 35 Ncm-1, indicating the scaffold's effectiveness in promoting bone regeneration and supporting implant therapy. The post-grafting planned implant position deviated overall by 2.4° compared with the initial restoratively driven implant plan pre-bone augmentation surgery. The patient reported low average daily pain during the first 48 h and no pain from Day 3. CONCLUSIONS: This proof-of-concept underscores the potential of 3D-printed scaffolds in personalized dental reconstruction and alveolar bone regeneration. It marks a significant step forward in integrating additive manufacturing technologies into clinical practice through a scaffold-guided bone regeneration (SGBR) approach. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000118707p).

3D printing for bone regeneration: challenges and opportunities for achieving predictability.

3D printing offers attractive opportunities for large-volume bone regeneration in the oro-dental and craniofacial regions. This is enabled by the development of CAD-CAM technologies that support the design and manufacturing of anatomically accurate meshes and scaffolds. This review describes the main 3D-printing technologies utilized for the fabrication of these patient-matched devices, and reports on their pre-clinical and clinical performance including the occurrence of complications for vertical bone augmentation and craniofacial applications. Furthermore, the regulatory pathway for approval of these devices is discussed, highlighting the main hurdles and obstacles. Finally, the review elaborates on a variety of strategies for increasing bone regeneration capacity and explores the future of 4D bioprinting and biodegradable metal 3D printing.

Tissue integration and biodegradation of soft tissue substitutes with and without compression: an experimental study in the rat.

OBJECTIVES: To analyze the influence of compression on tissue integration and degradation of soft tissue substitutes. MATERIAL AND METHODS: Six subcutaneous pouches in twenty-eight rats were prepared and boxes made of Al2O3 were implanted and used as carriers for soft tissue substitutes: a collagen matrix (MG), two volume-stable collagen matrices (FG/MGA), and a polycaprolactone scaffold(E). The volume-stable materials (FG/MGA/E) were further implanted with a twofold (2) and a fourfold (4) compression, created by the stacking of additional layers of the substitute materials. The samples were retrieved at 1, 2, and 12 weeks (10 groups, 3 time points, n = 5 per time point and group, overall, 150 samples). The area fraction of infiltrated fibroblasts and inflammatory cells was evaluated histologically. Due to within-subject comparisons, mixed models were conducted for the primary outcome. The level of significance was set at 5%. RESULTS: The area fraction of fibroblasts increased in all groups over time. At 12 weeks, the densely compressed materials FG4 (1.1%), MGA4 (1.7%), and MGA2 (2.5%) obtained lower values as compared to the other groups, ranging between 4.7 (E2) and 6.5% (MG). Statistically significant differences (p ≤ 0.05) were observed between groups FG4 vs MG/FG2/E/E4 as well as between MGA4 vs MG/FG2/E/E4 and E vs MGA2. CONCLUSIONS: Higher levels of compression led to delayed tissue integration. The effect of different compression levels was more distinct when compared to the differences between the materials. CLINICAL RELEVANCE: All biomaterials demonstrated tissue integration and a minimal concomitant inflammatory reaction. Clinically, it might be more favorable to obtain a sufficient flap release or to reduce the material size to improve the tissue integration processes.

Iron accumulation is associated with periodontal destruction in a mouse model of HFE-related haemochromatosis.

OBJECTIVE: To investigate the effect of Hfe gene mutation on the distribution of iron and periodontal bone loss in periodontal tissues. BACKGROUND DATA: It remains unclear how tissue iron loading affects the periodontium architectures in a genetic animal model of hereditary haemochromatosis (HH). METHODS: Male C57BL/6 Hfe -/- (8 weeks old) and wild-type (WT) mice were utilized to examine the iron distribution in periodontal tissues, as well as periodontal tissues changes using micro-computed tomography and histomorphometric analysis. Furthermore, tissue inflammatory mediators, bone markers and periodontal pathogens were carried out in PFA-fixed paraffin-embedded tissues using ELISA, RT-qPCR and genomic DNA qPCR, respectively. RESULTS: Excessive iron deposition was found in the periodontal ligament, gingiva and alveolar bone in Hfe -/- mice relative to their WT counterparts. This, in turn, was associated with significant periodontal bone loss, increased cemento-enamel junction-alveolar bone crest distance and decreased expression of molecules involved in bone development and turnover. Furthermore, the pro-inflammatory cytokine - interleukin 6 and periodontal bacteria - Campylobacter rectus were significantly increased in Hfe -/- mice compared with WT controls. CONCLUSION: Our results suggest that the iron loading in a mouse model of HH decreases alveolar bone formation and leads to alterations in the inflammatory state in the periodontium. Periodontal health should be assessed during the clinical assessment of HFE-HH patients.

Enamel matrix derivative promotes new bone formation in xenograft assisted maxillary anterior ridge preservation-A randomized controlled clinical trial.

OBJECTIVES: To compare the effectiveness of deproteinized bovine bone mineral with 10% collagen alone (DBBMC) or with enamel matrix derivative (DBBMC-EMD) in ridge preservation. METHODS: 42 maxillary anterior teeth were extracted and received either a DBBMC (control) or DBBMC-EMD (test) treatment protocol. CBCT taken before and 4 months after the extraction procedure was used to measure changes in alveolar ridge width (RW), buccal bone height (BH) and palatal bone height (PH). Bone cores were harvested during implant osteotomy preparation, and the samples processed histomorphometrically to assess the fraction of new bone (%NB), residual graft (%RG) and soft tissue matrix (%STM). RESULTS: Overall, both treatment groups showed significant reductions in mean RW from baseline to 4 months after extraction, but no significant change in either mean BH or PH over this time. When CBCT measurements were analysed according to the initial thickness of the buccal wall (BT < 1 mm vs. BT ≥ 1 mm), significant reductions in all ridge dimensions (RW, BH and PH) were noted in the <1 mm BT group. Histomorphometrically, the DBBMC-EMD test group showed significantly increased new bone formation (%NB): (control = 16.5 ± 6.9% cf.; test = 45.1 ± 8.8%) with less residual graft (%RG): (control = 36.8 ± 8.8% cf.; test = 20.3 ± 7.2%) compared to the DBBMC control group. CONCLUSIONS: Both DBBMC alone and DBBMC-EMD treated sites 4 months after extraction lost RW but showed no significant change in BH or PH. Irrespective of treatment, maxillary anterior teeth with thick initial buccal walls (≥1 mm) exhibited less alveolar ridge reduction 4 months after treatment. The addition of EMD to DBBMC resulted in more new bone formation in the test group.

Fibre guiding scaffolds for periodontal tissue engineering.

The periodontium is a highly hierarchically organized organ composed of gingiva, alveolar bone, periodontal ligament and cementum. Periodontitis leads to the destruction of hard and soft tissues ultimately leading to a loss of the teeth supporting apparatus. Current treatments are capable of limiting the disease progression; however, true regeneration, characterized by perpendicularly oriented periodontal ligament fibre attachment to cementum on the root surface remains challenging. Tissue engineering approaches have been developed to enhance regeneration via micro-engineered topographical features, purposely designed to guide the insertion of the regenerated ligament to the root surface. This review reports on the recent advancements in scaffold manufacturing methodologies for generating fibre guiding properties and provides a critical insight in the current limitations of these techniques for the formation of functional periodontal attachment.

Workflow for highly porous resorbable custom 3D printed scaffolds using medical grade polymer for large volume alveolar bone regeneration.

OBJECTIVES: This study investigates the design, workflow, and manufacture of highly porous, resorbable additively manufactured, 3-dimensional (3D) custom scaffolds for the regeneration of large volume alveolar bone defects. MATERIALS AND METHODS: Computed tomography (CT) scans of 5 posterior mandibular vertical bone defects were obtained. Surface masks (3D surface contours) of the recipient site were first isolated using a contrast threshold, transformed into 3D objects, and used to guide the formation of custom implant template models. To determine model accuracy and fit, the gap and overlap between the patient geometry models and the idealized template 3D models were quantified. Models were 3D printed from medical grade polycaprolactone (PCL) into porous scaffolds. For scaffold dimensional quantification, scaffolds were scanned using a micro-computed tomography (µCT) scanner. RESULTS: The design and printing processes each achieved dimensional errors of <200 µm on average. The average gap between the template implant model and the scanned scaffold model was found to be 74 ± 14 µm. The printed scaffold was confirmed as having a porosity of 83.91%, a mean polymer or filament thickness of 200 ± 46 µm, and a mean pore size of 590 ± 243 µm. CONCLUSION: The approach described in this study is straightforward, adaptable to a range of patient geometries, and results in the formation of reproducible, dimensionally accurate custom implants. These highly porous 3D structures manufactured from resorbable medical grade material represent a potentially transformative technology toward the clinical implementation of scaffold-guided bone regeneration procedures.

The influence of high-dose systemic zoledronate administration on osseointegration of implants with different surface topography.

AIM: To evaluate the influence of systemic zoledronate administration on the osseointegration of titanium implants with different surface topography in rat maxillae. METHODS: Twenty Sprague-Dawley rats were divided into two groups-test (bisphosphonate) and control (healthy). Bisphosphonate administration began three weeks prior to implant placement, and the animals received zoledronate (66 µg/kg) three times per week. Forty endosseous implants with a moderately rough (20 implants) or a turned surface (20 implants) were immediately placed bilaterally into extraction sockets of maxillary first molars. Animals were sacrificed after 14 and 28 days of healing, and en bloc specimens were harvested for histological and histomorphometric analysis. Osseointegration was quantified by measuring the percentage of bone-to-implant contact. RESULTS: Bone-to-implant contact (BIC) (mean ± SD) values of moderately rough and turned implants at day 14 in test group were 17.62 ± 6.68 and 10.69 ± 1.48, respectively, while in the control group, they were 46.36 ± 5.08 and 33.29 ± 8.89, respectively. At day 28, BIC values of moderately rough and turned implants in the test group were 25.94 ± 7.87 and 7.83 ± 4.30, respectively, while in the control group, they were 72.99 ± 6.60 and 47.62 ± 18.19, respectively. Statistically significant higher BIC values were measured on moderately rough implants compared to turned implants at 28 days, and the control group compared to the test group for both implant surfaces. Histological observations for the control and the test groups demonstrated initial bone formation around moderately rough implants not only on the surface of the parent bone, as was the case with the turned surfaced implants, but also along the implant surface itself. CONCLUSIONS: Systemic zoledronate administration negatively influences osseointegration. Osseointegration was enhanced adjacent to moderately rough compared to turned implants in both the presence and absence of systemic zoledronate administration. Therefore, topographical surface modification may partially offset the negative impact of zoledronate administration.

The effect of decellularized tissue engineered constructs on periodontal regeneration.

AIM: To evaluate the effect of decellularized tissue engineered constructs on cell differentiation in vitro and periodontal regeneration in vivo. MATERIALS AND METHODS: Periodontal ligament cell (PDLC) sheets were loaded on polycaprolactone (PCL) scaffolds and then decellularized. Constructs were assessed for their effect on allogenic PDLC and mesenchymal stem cell (MSC) differentiation in vitro, as evaluated by gene expression of bone and periodontal ligament tissue markers post-seeding. Expression of MSC marker STRO-1 was assessed by immunostaining. Decellularized constructs were evaluated in a rat periodontal defect model to assess their biocompatibility and tissue integration. Microcomputed topography (µCT) and histological assessment were performed to assess the regenerative potential of the constructs at 2 and 4 weeks postoperatively. RESULTS: There was upregulation of bone marker gene expression by PDLCs especially on the 14th day. MSCs lacked bone markers expression, but showed increased collagen I marker expression on day 14. STRO-1 expression by the MSCs decreased over the three timepoints when seeded on decellularized sheets. Histological assessment demonstrated the biocompatibility of the decellularized constructs in vivo. More new attachment formation was observed on the decellularized constructs compared to scaffold only controls. CONCLUSION: Decellularized tissue engineered constructs are capable of inducing cell differentiation in vitro and have the potential to facilitate periodontal regeneration in vivo.

3-Dimensional functionalized polycaprolactone-hyaluronic acid hydrogel constructs for bone tissue engineering.

AIM: Alveolar bone regeneration remains a significant clinical challenge in periodontology and dental implantology. This study assessed the mineralized tissue forming potential of 3-D printed medical grade polycaprolactone (mPCL) constructs containing osteoblasts (OB) encapsulated in a hyaluronic acid (HA)-hydrogel incorporating bone morphogenetic protein-7 (BMP-7). MATERIALS AND METHODS: HA-hydrogels containing human OB ± BMP-7 were prepared. Cell viability, osteogenic gene expression, mineralized tissue formation and BMP-7 release in vitro, were assessed by fluorescence staining, RT-PCR, histological/µ-CT examination and ELISA respectively. In an athymic rat model, subcutaneous ectopic mineralized tissue formation in mPCL-hydrogel constructs was assessed by µ-CT and histology. RESULTS: Osteoblast encapsulation in HA-hydrogels did not detrimentally effect cell viability, and 3-D culture in osteogenic media showed mineralized collagenous matrix formation after 6 weeks. BMP-7 release from the hydrogel was biphasic, sustained and increased osteogenic gene expression in vitro. After 4 weeks in vivo, mPCL-hydrogel constructs containing BMP-7 formed significantly more volume (mm3 ) of vascularized bone-like tissue. CONCLUSIONS: Functionalized mPCL-HA hydrogel constructs provide a favourable environment for bone tissue engineering. Although encapsulated cells contributed to mineralized tissue formation within the hydrogel in vitro and in vivo, their addition did not result in an improved outcome compared to BMP-7 alone.

Comparison of early osseointegration of SLA® and SLActive® implants in maxillary sinus augmentation: a pilot study.

OBJECTIVE: To assess the impact of a hydrophilic implant surface (SLActive® ) placed into augmented maxillary sinuses on bone-to-implant contact (BIC) and surrounding tissue composition when compared to a hydrophobic surface (SLA® ). MATERIAL AND METHODS: Four sheep underwent bilateral sinus augmentation. Each sinus received anorganic bovine bone mineral + autogenous bone (ABBM + AB). Sixteen implants were subsequently placed 12 weeks postgrafting with each sinus receiving a control (SLA® ) and test implant (SLActive® ). Two animals were sacrificed at 2 weeks and another two animals were sacrificed at 4 weeks postimplantation. The eight sinuses and 16 implants were processed for histomorphometry, which assessed bone-to-implant contact (%BIC) and tissue elements (woven bone - WB, lamellar bone - LB, soft tissue - ST) in the interthread region of implants within the augmented sinus. RESULTS: There was a statistically significant increase in %BIC at week 4 compared to the week 2 animals in both test (P < 0.005) and control (P < 0.005) groups. There was a statistically significant greater %BIC around test implants when compared to control implants in both week 2 (P < 0.05) and week 4 animals (P < 0.05). Greater %WB (11.17% ±6.82) and %LB (11.06% ±3.67) were seen in the test implants when compared to the control implants independent of time. This was only statistically significant for %LB (P < 0.05). A statistically significant reduction of 16.78% (±6.19) in %ST was noted in test implants when compared to control implants (P < 0.05) independent of time. CONCLUSION: Both time and the use of hydrophilic implant surface had a positive impact on %BIC around implants placed into augmented maxillary sinuses. Hydrophilic implant surfaces also had a positive impact on surrounding tissue composition. Larger trials are needed to better assess and detect differences between these two surfaces in augmented maxillary sinuses.

A histomorphometric assessment of collagen-stabilized anorganic bovine bone mineral in maxillary sinus augmentation - a randomized controlled trial in sheep.

OBJECTIVE: To histomorphometrically compare the use of collagen-stabilized anorganic bovine bone (ABBM-C) (test) to anorganic bovine bone + autogenous bone (ABBM + AB) (control) in maxillary sinus augmentation. MATERIALS AND METHODS: Nine sheep underwent bilateral sinus augmentation. Each sinus was randomized to receive either control or test bone graft. Three animals were sacrificed at 8 weeks, and six animals were sacrificed at 16 weeks post-grafting. The 18 sinuses were processed for histomorphometry, which assessed the area fraction of new bone (%NB), residual graft (%RG) and soft tissue components (% STM), as well as graft particle osseointegration (% OI), within three zones equally distributed from the augmented sinus floor. RESULTS: At week 16, a significant increase in %NB was evident across all three zones in the control group when compared to week 8. A significantly greater %NB was evident in the control group when compared to the test group in zones 2 (P < 0.001) and 3 (P < 0.001). There was a significant increase in %OI in week 16 when compared to week 8 across all three zones in the control group (P < 0.001). %OI in the control group was significantly greater across all three zones when compared to the test group at week 16 (P < 0.001). Zone was found to be a significant main effect (P < 0.001) that was independent of time and treatment with decreasing %OI in distant zones. %RG did not significantly change with time for both groups. There was a significant reduction in %ST in week 16 when compared to week 8 across all three zones in the control group (P < 0.001). %ST in the test group was significantly greater across all zones when compared to the control group at week 16 (P < 0.001). CONCLUSION: Both groups exhibited very similar histomorphometric measurements in the zones proximal to the resident sinus wall. The % NB and % OI were greatest in the zones proximal to resident bony walls and gradually decreased as the distance from the proximal walls increased. There was greater % NB and % OI in the control group when compared to the test group in the distant zone.

A histomorphometric assessment of collagen-stabilized anorganic bovine bone mineral in maxillary sinus augmentation - a prospective clinical trial.

OBJECTIVE: To histomorphometrically compare the use of collagen-stabilized anorganic bovine bone (ABBM-C) (test) to anorganic bovine bone + autogenous bone (ABBM + AB) (control) in maxillary sinus augmentation. MATERIALS AND METHODS: Forty (n = 40 sinuses) patients underwent sinus augmentation and received either control (20 sinuses) or test bone graft (20 sinuses). Bone samples were harvested from the augmented sinuses 5 months postgrafting. The samples were processed for histomorphometry, which assessed within the primary region of interest (ROI-1), the area fraction of new bone (%NB), graft particle osseointegration (% OI), residual graft (%RG), and soft tissue components (% STM). The same analysis was also carried out in a second region of interest (ROI-2) located in a zone 1 mm proximal to the previous maxillary sinus floor. RESULTS: In both ROI-1 and ROI-2, the mean % NB, %RG, and %STM in the control group were similar to mean values in the test group. The % OI was significantly greater in the control group (42.0 +/- 26.8) when compared to the test group (19.6 +/- 27.3) in ROI-2 (P < 0.05). No statistically significant differences were seen when ROI-1 and ROI-2 were compared except for improved %OI in ROI-2 in the control group. The mean proportion of lamellar bone to woven bone in the control group (1.22 ± 1.48) was significantly greater than the test group (0.38 ± 0.29) (P < 0.05). CONCLUSION: ABBM-C exhibited very similar histomorphometric parameters to the composite graft of ABBM + AB. The ABBM + AB group was more mature as indicated by the significantly greater proportion of lamellar bone when compared to the ABBM-C. Improved % OI was seen in the zone proximal to the resident bony floor in the ABBM + AB group. Based on histological assessment, ABBM-C is a suitable bone substitute for the purposes of maxillary sinus augmentation. Its clinical utility may be indicated in cases of sinus membrane perforation and insufficient autogenous bone in the local area.

Advanced tissue engineering scaffold design for regeneration of the complex hierarchical periodontal structure.

AIM: This study investigated the ability of an osteoconductive biphasic scaffold to simultaneously regenerate alveolar bone, periodontal ligament and cementum. MATERIALS AND METHODS: A biphasic scaffold was built by attaching a fused deposition modelled bone compartment to a melt electrospun periodontal compartment. The bone compartment was coated with a calcium phosphate (CaP) layer for increasing osteoconductivity, seeded with osteoblasts and cultured in vitro for 6 weeks. The resulting constructs were then complemented with the placement of PDL cell sheets on the periodontal compartment, attached to a dentin block and subcutaneously implanted into athymic rats for 8 weeks. Scanning electron microscopy, X-ray diffraction, alkaline phosphatase and DNA content quantification, confocal laser microscopy, micro computerized tomography and histological analysis were employed to evaluate the scaffold's performance. RESULTS: The in vitro study showed that alkaline phosphatase activity was significantly increased in the CaP-coated samples and they also displayed enhanced mineralization. In the in vivo study, significantly more bone formation was observed in the coated scaffolds. Histological analysis revealed that the large pore size of the periodontal compartment permitted vascularization of the cell sheets, and periodontal attachment was achieved at the dentin interface. CONCLUSIONS: This work demonstrates that the combination of cell sheet technology together with an osteoconductive biphasic scaffold could be utilized to address the limitations of current periodontal regeneration techniques.

Melt electrowriting scaffolds with fibre-guiding features for periodontal attachment.

Periodontal regeneration requires the re-attachment of oblique and perpendicular periodontal ligament (PDL) fibres to newly formed cementum and alveolar bone, which has proven elusive with existing approaches. In this study, multiple fibre-guiding biphasic tissue engineered constructs were fabricated by melt electrowriting. The biphasic scaffolds were 95 % porous and consisted of a pore size gradient bone compartment and periodontal compartment made of fibre-guiding channels with micro-architectural features ranging from 100 to 60 µm aimed to direct PDL fibre alignment and attachment. In vitro evaluations over 3 and 7 days demonstrated a marked improvement in collagen fibre orientation (over 60 % fully aligned) for scaffolds with micro-architecture ≤100 µm. The biphasic scaffolds were placed on a dentine slice and implanted ectopically, and this demonstrated that all micro-channels groups facilitated oblique and perpendicular alignment and attachment on the dentine with a mean nuclei angle and mean collagen fibre angle of approximately 60° resembling the native periodontal ligament attachment. A further in vivo testing using a surgically created rodent periodontal model highlighted the 80 µm micro-channel group's effectiveness, showing a significant increase in oblique PDL fibre attachment (72 %) and periodontal regeneration (56 %) when compared to all other groups onto the tooth root compared to control groups. Further to this, immunohistochemistry demonstrated the presence of periostin in the newly formed ligament indicating that functional regeneration occurred These findings suggest that scaffold micro-architectures of 100 µm or below can play a crucial role in directing periodontal tissue regeneration, potentially addressing a critical gap in periodontal therapy. STATEMENT OF SIGNIFICANCE: Periodontal regeneration remains a significant clinical challenge. Essential to restoring dental health and function is the proper attachment of the periodontal ligament, which is functionally oriented, to regenerated bone and cementum. Our research presents an innovative biphasic scaffold, utilizing Melt Electrowriting to systematically guide tissue growth. Distinct from existing methods, our scaffold is highly porous, adaptable, and precisely guides periodontal ligament fibre attachment to the opposing tooth root and alveolar bone interfaces, a critical step for achieving periodontal functional regeneration. Our findings not only bridge a significant gap in biomaterial driven tissue guidance but also promise more predictable outcomes for patients, marking a transformative advancement in the field.

Hydrogel based soft tissue expanders for orodental reconstruction.

Tension-free flap closure to prevent soft tissue dehiscence is a prerequisite for successful bone augmentation in orodental reconstructive surgery. Since soft tissue contour follows the underlying jaw bony architecture, resorption of alveolar (jaw) bone limits the availability of soft tissue for wound closure following major bone reconstruction, required to facilitate oral rehabilitation with endosseous dental implants following tooth loss. Although there are several clinical procedures to increase soft tissue volume, these techniques are complicated and technically demanding. Soft tissue expansion, an established technique in reconstructive surgery, is an ideal alternative to generate surplus soft tissue prior to bone augmentation and dental implant placement. Increase in tissue volume can be achieved by using soft tissue expanders (STEs). Contemporary STEs have evolved from silicone balloons to osmotically inflating hydrogel-based systems. Here, we provide an overview of STEs in clinical oral surgery, outline the current research in STEs, and an update on recent clinical trials as well as the associated complications. Also, the mechanism governing soft tissue expansion and the critical factors that control the expansion process are covered. Design considerations for STEs for intraoral applications are given particular attention. Finally, we present our perspectives on utilization of minimally invasive methods to administer STEs for orodental applications. STATEMENT OF SIGNIFICANCE: Soft tissue expansion is required for a range of reconstructive applications and more notably in regenerative dentistry for vertical bone augmentation. This review describes the commercially available soft tissue expanders along with the latest systems being currently developed. This review insightfully discusses the biological and physical mechanisms leading to soft tissue expansion and critically assesses the design criteria of soft tissue expanders. A particular focus is given on the development of a new generation of hydrogel-based soft tissue expanders; their chemistry and required physical properties for tissue expansion is described and the obstacles towards clinical translations are identified. Finally, the review elaborates on promising minimally invasive injectable hydrogel-based tissue expanders and highlights the beneficial features of these systems.

Workflow for Fabricating 3D-Printed Resorbable Personalized Porous Scaffolds for Orofacial Bone Regeneration.

Resorption of alveolar bone following tooth extraction is a physiological process that can often prevent the placement of dental implants due to the limited bone remaining. In severe cases, vertical bone augmentation, which aims to restore bone in an extraskeletal dimension (outside of the skeletal envelope), is required prior to implant placement. While current treatment strategies rely on autologous grafts, or "Guided Bone Regeneration" involving the placement of particulate bone grafting biomaterials under a protective membrane, the field is shifting to patient-matched solutions. Herein, we describe the various steps required for modeling the patient data, creating the patient-matched scaffold geometry and 3D-printing using the biodegradable polymer polycaprolactone for application in the oro-dental and craniofacial areas.

Additively manufactured polyethylene terephthalate scaffolds for scapholunate interosseous ligament reconstruction.

The regeneration of the ruptured scapholunate interosseous ligament (SLIL) represents a clinical challenge. Here, we propose the use of a Bone-Ligament-Bone (BLB) 3D-printed polyethylene terephthalate (PET) scaffold for achieving mechanical stabilisation of the scaphoid and lunate following SLIL rupture. The BLB scaffold featured two bone compartments bridged by aligned fibres (ligament compartment) mimicking the architecture of the native tissue. The scaffold presented tensile stiffness in the range of 260 ± 38 N/mm and ultimate load of 113 ± 13 N, which would support physiological loading. A finite element analysis (FEA), using inverse finite element analysis (iFEA) for material property identification, showed an adequate fit between simulation and experimental data. The scaffold was then biofunctionalized using two different methods: injected with a Gelatin Methacryloyl solution containing human mesenchymal stem cell spheroids (hMSC) or seeded with tendon-derived stem cells (TDSC) and placed in a bioreactor to undergo cyclic deformation. The first approach demonstrated high cell viability, as cells migrated out of the spheroid and colonised the interstitial space of the scaffold. These cells adopted an elongated morphology suggesting the internal architecture of the scaffold exerted topographical guidance. The second method demonstrated the high resilience of the scaffold to cyclic deformation and the secretion of a fibroblastic related protein was enhanced by the mechanical stimulation. This process promoted the expression of relevant proteins, such as Tenomodulin (TNMD), indicating mechanical stimulation may enhance cell differentiation and be useful prior to surgical implantation. In conclusion, the PET scaffold presented several promising characteristics for the immediate mechanical stabilisation of disassociated scaphoid and lunate and, in the longer-term, the regeneration of the ruptured SLIL.

The use of an electrostatic lens to enhance the efficiency of the electrospinning process.

Electrospun scaffolds manufactured using conventional electrospinning configurations have an intrinsic thickness limitation, due to a charge build-up at the collector. To overcome this limitation, an electrostatic lens has been developed that, at the same relative rate of deposition, focuses the polymer jet onto a smaller area of the collector, resulting in the fabrication of thick scaffolds within a shorter period of time. We also observed that a longer deposition time (up to 13 h, without the intervention of the operator) could be achieved when the electrostatic lens was utilised, compared to 9­10 h with a conventional processing set-up and also showed that fibre fusion was less likely to occur in the modified method. This had a significant impact on the mechanical properties, as the scaffolds obtained with the conventional process had a higher elastic modulus and ultimate stress and strain at short times. However, as the thickness of the scaffolds produced by the conventional electrospinning process increased, a 3-fold decrease in the mechanical properties was observed. This was in contrast to the modified method, which showed a continual increase in mechanical properties, with the properties of the scaffold finally having similar mechanical properties to the scaffolds obtained via the conventional process at longer times. This "focusing" device thus enabled the fabrication of thicker 3-dimensional electrospun scaffolds (of thicknesses up to 3.5 mm), representing an important step towards the production of scaffolds for tissue engineering large defect sites in a multitude of tissues.

The utilisation of resolvins in medicine and tissue engineering.

Recent advances in the field of regenerative medicine and biomaterial science have highlighted the importance of controlling immune cell phenotypes at the biomaterial interface. These studies have clearly indicated that a rapid resolution of the inflammatory process, mediated by a switch in the macrophage population towards a reparative phenotype, is essential for tissue regeneration to occur. While various biomaterial surfaces have been developed in order to impart immunomodulatory properties to the resulting constructs, an alternative strategy involving the use of reparative biological cues, known as resolvins, is emerging in regenerative medicine. This review reports on the mechanisms via which resolvins participate in the resolution of inflammation and describes their current utilisation in pre-clinical and clinical settings, along with their effectiveness when combined with biomaterial constructs in tissue engineering applications. STATEMENT OF SIGNIFICANCE: The resolution of the inflammatory process is necessary for achieving tissue healing and regeneration. Resolvins are lipid mediators and play a key role in the resolution of the inflammatory response and can be used in as biological cues to promote tissue regeneration. This review describes the various biological inflammatory mechanisms and pathways involving resolvins and how their action results in a pro-healing response. The use of these molecules in the clinical setting is then summarised for various applications along with their limitations. Lastly, the review focuses on the emergence resolvins in tissue engineering products including the use of a more stable form which holds greater prospect for regenerative purposes.