Fabrication and characterization of 3D-printed composite scaffolds of coral-derived hydroxyapatite nanoparticles/polycaprolactone/gelatin carrying doxorubicin for bone tissue engineering.

In this study, nanocomposite scaffolds of hydroxyapatite (HA)/polycaprolactone (PCL)/gelatin (Gel) with varying amounts of HA (42-52 wt. %), PCL (42-52 wt. %), and Gel (6 wt. %) were 3D printed. Subsequently, a scaffold with optimal mechanical properties was utilized as a carrier for doxorubicin (DOX) in the treatment of bone cancer. For this purpose, HA nanoparticles were first synthesized by the hydrothermal conversion of Acropora coral and characterized by using different techniques. Also, a compression test was performed to investigate the mechanical properties of the fabricated scaffolds. The mineralization of the optimal scaffold was determined by immersing it in simulated body fluid (SBF) solution for 28 days, and the biocompatibility was investigated by seeding MG-63 osteoblast-like cells on it after 1-7 days. The obtained results showed that the average size of the synthesized HA particles was about 80 nm. The compressive modulus and strength of the scaffold with 47 wt. % HA was reported to be 0.29 GPa and 9.9 MPa, respectively, which was in the range of trabecular bones. In addition, the scaffold surface was entirely coated with an apatite layer after 28 days of soaking in SBF. Also, the efficiency and loading percentage of DOX were obtained as 30.8 and 1.6%, respectively. The drug release behavior was stable for 14 days. Cytotoxicity and adhesion evaluations showed that the fabricated scaffold had no negative effects on the viability of MG-63 cells and led to their proliferation during the investigated period. From these results, it can be concluded that the HA/PCL/Gel scaffold prepared in this study, in addition to its drug release capability, has good bioactivity, mechanical properties, and biocompatibility, and can be considered a suitable option for bone tumor treatment.

In vivo evaluation of bone regeneration using ZIF8-modified polypropylene membrane in rat calvarium defects.

AIM: The profound potential of zeolitic imidazolate framework 8 (ZIF8) thin film for inducing osteogenesis has been previously established under in vitro conditions. As the next step towards the clinical application of ZIF8-modified substrates in periodontology, this in vivo study aimed to evaluate the ability of the ZIF8 crystalline layer to induce bone regeneration in an animal model defect. MATERIALS AND METHODS: Following the mechanical characterization of the membranes and analysing the in vitro degradation of the ZIF8 layer, in vivo bone regeneration was evaluated in a critical-sized (5-mm) rat calvarial bone defect model. For each animal, one defect was randomly covered with either a polypropylene (PP) or a ZIF8-modified membrane (n = 7 per group), while the other defect was left untreated as a control. Eight weeks post surgery, bone formation was assessed by microcomputed tomography scanning, haematoxylin and eosin staining and immunohistochemical analysis. RESULTS: The ZIF8-modified membrane outperformed the PP membrane in terms of mechanical properties and revealed a trace Zn+2 release. Results of in vivo evaluation verified the superior barrier function of the ZIF8-coated membrane compared with pristine PP membrane. Compared with the limited marginal bone formation in the control and PP groups, the defect area was almost filled with mature bone in the ZIF8-coated membrane group. CONCLUSIONS: Our results support the effectiveness of the ZIF8-coated membrane as a promising material for improving clinical outcomes of guided bone regeneration procedures, without using biological components.

Potential neuroprotective effect of stem cells from apical papilla derived extracellular vesicles enriched by lab-on-chip approach during retinal degeneration.

Retinal degeneration (RD) is recognized as a frequent cause of visual impairments, including inherited (Retinitis pigmentosa) and degenerative (age-related macular) eye diseases. Dental stem cells (DSCs) have recently demonstrated a promising neuroprotection potential for ocular diseases through a paracrine manner carried out by extracellular vesicles (EVs). However, effective isolation of EVs is still challenging, and isolation methods determine the composition of enriched EVs and the subsequent biological and functional effects. In the present study, we assessed two enrichment methods (micro-electromechanical systems and ultrafiltration) to isolate the EVs from stem cells from apical papilla (SCAP). The size distribution of the corresponding isolates exhibited the capability of each method to enrich different subsets of EVs, which significantly impacts their biological and functional effects. We confirmed the neuroprotection and anti-inflammatory capacity of the SCAP-EVs in vitro. Further experiments revealed the possible therapeutic effects of subretinal injection of SCAP-EVs in the Royal College of Surgeons (RCS) rat model. We found that EVs enriched by the micro-electromechanical-based device (MEMS-EVs) preserved visual function, reduced retinal cell apoptosis, and prevented thinning of the outer nuclear layer (ONL). Interestingly, the effect of MEMS-EVs was extended to the retinal ganglion cell/retinal nerve fiber layer (GCL/RNFL). This study supports the use of the microfluidics approach to enrich valuable subsets of EVs, together with the choice of SCAP as a source to derive EVs for cell-free therapy of RD.

AC electrokinetic isolation and detection of extracellular vesicles from dental pulp stem cells: Theoretical simulation incorporating fluid mechanics.

Extracellular vesicles (EVs) are cell-derived nanoscale vesicles involved in intracellular communication and the transportation of biomarkers. EVs released by mesenchymal stem cells have been recently reported to play a role in cell-free therapy of many diseases. However, the demand for better research tools to replace the tedious conventional methods used to study EVs is getting stronger. EVs' manipulation using alternating current (AC) electrokinetic forces in a microfluidic device has appeared to be a reliable and sensitive diagnosis and trapping technique. Given that different AC electrokinetic forces may contribute to the overall motion of particles and fluids in a microfluidic device, EVs' electrokinetic trapping must be examined considering all dominant forces involved depending on the experimental conditions. In this paper, AC electrokinetic trapping of EVs using an interdigitated electrode arrays is investigated. A 2D numerical simulation incorporating the two significant AC electrokinetic phenomena (Dielectrophoresis and AC electroosmosis) has been performed. Theoretical predictions are then compared with experimental results and allow for a plausible explanation of observations inconsistent with DEP theory. It is demonstrated that the inconsistencies can be attributed to a significant extent to the contribution of the AC electroosmotic effect.

Hedgehog signalling is dispensable in the proliferation of stem cells from human exfoliated deciduous teeth.

The hedgehog (Hh) signalling pathway is one of the key regulators in development with a dual role in cell fate specification, proliferation, and survival on different target cells. We have investigated the effect of recombinant sonic hedgehog (r-SHH) on extracted multipotent stem cells from human exfoliated deciduous teeth (SHED), which represent a potential stem cell population for therapeutic applications. Cell proliferation and cycle assays shown that r-SHH did not have a distinctive effect on cell cycle progression, nor did it increase cell number over a wide range of concentrations. Quantitative polymerase chain reaction (Q-PCR) also suggests that r-SHH treatment has no demonstrable influence on expression of proliferative genes (CCNE1 and KI67); in contrast, the anti-proliferative gene (CDKN1A) is overexpressed in response to SHH. Our findings have suggested the possibility that SHEDs demonstrate a different potential from human bone marrow mesenchymal stem cells (h-BMSCs) and dorsal neural progenitor in response to growth factors such as SHH.

Isolation and characterization of human periodontal ligament stem cells under the terms of use in clinical application: A pilot study.

Background: The aim of the present study is to determine the possibility of isolation and characterization of the human periodontal ligament stem cells (hPDLSCs) using limited harvested periodontal ligament (PDL) tissue of only one patient's wisdom teeth (2-4 teeth) under the more compatible terms of use in clinical application without using the fetal bovine serum (FBS). Materials and Methods: In this pilot study, hPDLSCs were isolated from the impacted third molar, and tissue was scraped from the roots of the impacted third molar of 10 volunteers to enzymatically digest using collagenase. The cells were sub-cultured. The samples of the first seven patients and half of the eighth patient's sample were cultured in alpha modified of Eagle's medium (α-MEM) (-FBS) medium and the other part of the eighth patient's sample was cultured with prior medium supplemented with +FBS 15% as a control of the cultivation protocol. While for the past two patients (9th and 10th the α-MEM medium was supplemented with L-Glutamine, anti/anti 2X, and 20% knock-out serum replacement (KSR). Two more nutritious supplements (N2 and B27) were added to the medium of the tenth sample. Flow-cytometric analysis for the mesenchymal stem cell surface markers CD105, CD45, CD90, and CD73 was performed. Subsequent polymerase chain reaction was undertaken on three samples cultured with two growth media. Results: Cultivation failed in some of the samples because of the lack of cell adhesion to the culturing dish bottom (floating cells), but it was successful for the 9th and 10th patients, which were cultured in the α-MEM serum supplemented with KSR 20%. Flow cytometry analysis was positive for CD105, CD90, and CD73 and negative for CD45. The PDL stem cells (PDLSCs) expressed CD105, CD45, and CD90 but were poor for CD73. Conclusion: According to the limited number of sample tests in this study, isolation and characterization of PDLSCs from collected PDL tissue of one patient's wisdom teeth (2-4) may be possible by the proper setup in synthetic FBS-free serum.

Comparison of Adhesion and Proliferation of Human Gingival Fibroblasts on Acellular Dermal Matrix with and without Low Level Diode Laser Irradiation, an in vitro Study.

Statement of the Problem: In recent years, regeneration of periodontal soft tissues in the reconstruction of periodontal defects and the finding of suitable membranes and graft materials for the placement of autogenous grafts have been of great interest in various studies. In this regard, the proliferation and adhesion of regenerative cells are two linchpins of the complete regenerative process. Purpose: This study aimed to evaluate the effects of low-level laser beams on the attachment and the proliferation of human gingival fibroblasts in the presence of acellular dermal matrix (ADM). Materials and Method: All the experiments were conducted compared to tissue culture plate in four groups as follows: (1) Fibroblast+ADM+laser, (2) Fibroblast+ADM+ no laser, (3) Fibroblast + laser radiation, and (4) Fibroblast+ no laser. In this experimental study, the primary attachment was evaluated by passing 8h from seeding of 5×105 gingival fibroblasts with or without a single dose (15.6 J/cm2) of laser radiation. Cell proliferation rate was also examined at 24, 48, and 72 hours after cell culture, following exposure to 5.2 J/cm2 of laser at each day of examination. Thereafter, fibroblasts were incubated under the normal culture condition (at 37°C, 5% CO2) in high glucose Dulbecco's Modified Eagle's medium (DMEM) medium supplemented with 10% fetal bovine serum, 1% glutamax, and 1% penicillin/streptomycin. Subsequently, the cellular viability was assessed on each time point using MTS calorimetric assay. The obtained data were statistically analyzed by applying ANOVA and Tukey tests. Results: There was a significant difference among the means of these four groups in terms of the proliferation of fibroblasts at 24, 48 and 72 hours (p< 0.001). Moreover, there was no significant difference among the means of two groups in terms of fibroblastic attachment in 8 hours (p< 0.2). The fibroblast group has shown the highest proliferation rate among all groups after laser radiation. Conclusion: It was indicated that the laser radiation increases the fibroblast cell proliferation. Accordingly, although this increase was higher in the fibroblast group alone compared to the fibroblasts cultured on acellular dermal matrix, the laser radiation did not significantly increase the attachment of fibroblast cells to acellular dermal matrix.

Assessment of Cytotoxicity and Odontogenic/Osteogenic Differentiation Potential of Nano-Dentine Cement Against Stem Cells from Apical Papilla.

OBJECTIVE: Assessment of the cytotoxicity of novel calcium silicate-based cement is imperative in endodontics. This experimental study aimed to assess the cytotoxicity and odontogenic/osteogenic differentiation potential of a new calcium silicate/pectin cement called Nano-dentine against stem cells from the apical papilla (SCAPs). MATERIALS AND METHODS: In this experimental study, the cement powder was synthesized by the sol-gel technique. Zirconium oxide was added as opacifier and Pectin, a plant-based polymer, and calcium chloride as the liquid to prepare the nano-based dental cement. Thirty-six root canal dentin blocks of human extracted single-canal premolars with 2 mm height, flared with #1, 2 and 3 Gates-Glidden drills were used to prepare the cement specimens. The cement, namely mineral trioxide aggregate (MTA), Biodentine, and the Nano-dentine were mixed according to the manufacturers' instructions and applied to the roots of canal dentin blocks. The cytotoxicity and odontogenic/osteogenic potential of the cement were evaluated by using SCAPs. RESULTS: SCAPs were characterized by the expression of routine mesenchymal cell markers and differentiation potential to adipocytes, osteoblasts, and chondrocytes. Cement displayed no significant differences in cytotoxicity or calcified nodules formation. Gene expression analysis showed that all three types of cement induced significant down- regulation of COLA1; however, the new cement induced significant up-regulation of RUNX2 and SPP1 compared to the control group and MTA. The new cement also induced significant up-regulation of TGFB1 and inducible nitric oxide synthase (iNOS) compared with Biodentine and MTA. CONCLUSION: The new Nano-dentin cement has higher odontogenic/osteogenic potential compared to Biodentine and MTA for differentiation of SCAPs to adipocytes, osteoblasts, and chondrocytes.

Recent advances in polymeric nanostructured ion selective membranes for biomedical applications.

Nano structured ion-selective membranes (ISMs) are very attractive materials for a wide range of sensing and ion separation applications. The present review focuses on the design principles of various ISMs; nanostructured and ionophore/ion acceptor doped ISMs, and their use in biomedical engineering. Applications of ISMs in the biomedical field have been well-known for more than half a century in potentiometric analysis of biological fluids and pharmaceutical products. However, the emergence of nanotechnology and sophisticated sensing methods assisted in miniaturising ion-selective electrodes to needle-like sensors that can be designed in the form of implantable or wearable devices (smartwatch, tattoo, sweatband, fabric patch) for health monitoring. This article provides a critical review of recent advances in miniaturization, sensing and construction of new devices over last decade (2011-2021). The designing of tunable ISM with biomimetic artificial ion channels offered intensive opportunities and innovative clinical analysis applications, including precise biosensing, controlled drug delivery and early disease diagnosis. This paper will also address the future perspective on potential applications and challenges in the widespread use of ISM for clinical use. Finally, this review details some recommendations and future directions to improve the accuracy and robustness of ISMs for biomedical applications.

Mechanobiology of Dental Pulp Stem Cells at the Interface of Aqueous-Based Fabricated ZIF8 Thin Film.

The limited knowledge on how biological systems sense and respond to the mechanical properties of metal-organic framework (MOF) thin films is a critical restriction factor for their extensive usage. To bridge this gap, we performed an in vitro study for defining and linking surface characteristics at the interface of the zeolitic imidazolate framework-8 (ZIF8) thin layer to stem cell behavior. First, the physio-mechanical properties of the ZIF8 layer grown on polydopamine (PDA) and tannic acid (TA) layers have been studied. The response of dental pulp stem cells (DPSCs) to different surface states was examined. The results showed that the uniform crystalline microstructure of the ZIF8 on PDA and TA effectively led to the 61- and 388-fold increased surface roughness, 3- and 2.5-fold moderated elastic modulus, almost 3-fold elevated surface free energy, and highly charged surfaces (ζ = -60 mV for TA/ZIF8), respectively. Beyond the inherent bioactivity of the ZIF8 layer, these substrate cues promoted advanced cell adhesion (∼two times) and high proliferation rate. Furthermore, we found a substantial increment in the differentiation efficiency of DPSCs on the ZIF8 layer, in a way that the expression of functional adipocyte (PPARG) and osteoblast (SPP1) markers was, respectively, elevated around 30 000- and 10 000-fold on the TA/ZIF8-coated silicon wafer (SW). Our findings support the impact of fabrication strategy on the biointerface properties of the ZIF8 layer and bring SW/TA/ZIF8 as a robust platform for managing stem cells for biomedical applications.

Enhancing osteoregenerative potential of biphasic calcium phosphates by using bioinspired ZIF8 coating.

Biphasic calcium phosphate ceramics (BCPs) have been extensively used as a bone graft in dental clinics to reconstruct lost bone in the jaw and peri-implant hard tissue due to their good bone conduction and similar chemical structure to the teeth and bone. However, BCPs are not inherently osteoinductive and need additional modification and treatment to enhance their osteoinductivity. The present study aims to develop an innovative strategy to improve the osteoinductivity of BCPs using unique features of zeolitic imidazolate framework-8 (ZIF8). In this method, commercial BCPs (Osteon II) were pre-coated with a zeolitic imidazolate framework-8/polydopamine/polyethyleneimine (ZIF8/PDA/PEI) layer to form a uniform and compact thin film of ZIF8 on the surface of BCPs. The surface morphology and chemical structure of ZIF8 modified Osteon II (ZIF8-Osteon) were confirmed using various analytical techniques such as XRD, FTIR, SEM, and EDX. We evaluated the effect of ZIF8 coating on cell attachment, growth, and osteogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs). The results revealed that altering the surface chemistry and topography of Osteon II using ZIF8 can effectively promote cell attachment, proliferation, and bone regeneration in both in vitro and in vivo conditions. In conclusion, the method applied in this study is simple, low-cost, and time-efficient and can be used as a versatile approach for improving osteoinductivity and osteoconductivity of other types of alloplastic bone grafts.

The effect of laser irradiation and doxycycline application on the production of matrix metalloproteinase-8 and collagen I from cultured human periodontal ligament cells.

BACKGROUND: Periodontal ligament fibroblasts (PDLF) play a key role in periodontal wound healing and tooth-supporting structures. Various approaches have been tried to enhance the fibroblastic activity such as laser irradiation or doxycycline application. The current study explored the influence of laser irradiation and doxycycline application on human PDLF. The aim of the study was the effect of low-level laser treatment and doxycycline application on the expression of collagen I and matrix metalloproteinase-8 (MMP8) from cultured human periodontal ligament cells. MATERIALS AND METHODS: In this experimental study After preparation of human PDLF in three replications, they were divided into five treatment groups. The first group was day 0, which was used for standardization. The second group was the control group, which received no treatment within 4 days of the study. The third group was treated with doxycycline 30, daily for 4 consecutive days. The fourth group was treated with diode laser 2 daily for 4 consecutive days. The fifth group was treated with both doxycycline and laser irradiation pertaining to the third and fourth groups. After 4 days of treatment, cells were tested for collagen I and MMP-8 secretion through real-time-polymerase chain reaction and ELISA reader. The data were analyzed using the ANOVA and least significant difference pair tests ( P < 0.05 ). RESULTS: Treatment of human PDLF either with diode laser or doxycycline reduced the secretion of MMP-8 significantly. The maximum reduction was related to doxycycline application. Regarding collagen, I, only doxycycline application significantly increased collagen I secretion. Other groups showed no significant increase in collagen I secretion. CONCLUSION: This study showed that treatment of human PDLF either with diode laser or doxycycline significantly reduced MMP-8. Treatment with doxycycline significantly increased the secretion of collagen I.

ZIF-8 Modified Polypropylene Membrane: A Biomimetic Cell Culture Platform with a View to the Improvement of Guided Bone Regeneration.

PURPOSE: Despite the significant advances in modeling of biomechanical aspects of cell microenvironment, it remains a major challenge to precisely mimic the physiological condition of the particular cell niche. Here, the metal-organic frameworks (MOFs) have been introduced as a feasible platform for multifactorial control of cell-substrate interaction, given the wide range of physical and mechanical properties of MOF materials and their structural flexibility. RESULTS: In situ crystallization of zeolitic imidazolate framework-8 (ZIF-8) on the polydopamine (PDA)-modified membrane significantly raised surface energy, wettability, roughness, and stiffness of the substrate. This modulation led to an almost twofold increment in the primary attachment of dental pulp stem cells (DPSCs) compare to conventional plastic culture dishes. The findings indicate that polypropylene (PP) membrane modified by PDA/ZIF-8 coating effectively supports the growth and proliferation of DPSCs at a substantial rate. Further analysis also displayed the exaggerated multilineage differentiation of DPSCs with amplified level of autocrine cell fate determination signals, like BSP1, BMP2, PPARG, FABP4, ACAN, and COL2A. Notably, osteogenic markers were dramatically overexpressed (more than 100-folds rather than tissue culture plate) in response to biomechanical characteristics of the ZIF-8 layer. CONCLUSION: Hence, surface modification of cell culture platforms with MOF nanostructures proposed as a powerful nanomedical approach for selectively guiding stem cells for tissue regeneration. In particular, PP/PDA/ZIF-8 membrane presented ideal characteristics for using as a barrier membrane for guided bone regeneration (GBR) in periodontal tissue engineering.

Cytotoxicity Evaluation of The Bioresorbable and Titanium Plates/Screws Used in Maxillofacial Surgery on Gingival Fibroblasts and Human Mesenchymal Bone Marrow Stem Cells.

OBJECTIVE: Bioresorbable and titanium plates/screws are considered as a standard treatment for fixation of the bone segments of craniofacial area and paying attention to their biocompatibility is an important issue along with other aspects of application. The purpose of the study was to evaluate the cell viability of two types of plate and screw used in maxillofacial surgeries in contact with gingival fibroblasts and bone marrow stem cells. MATERIALS AND METHODS: In this experimental study after extraction and cultivation of cells from healthy human gingival tissue and alveolar bone of jaw, cytotoxicity of device was evaluated. In direct contact method, samples had near vicinity contact with the both cell lines and in indirect contact method, by-products released, like ions, from samples after 8 weeks were used to assess cytotoxicity. Then cytotoxicity was evaluated on the 2nd, 4th and 6th day with MTS tests and microscopy. The data were analyzed by one-way ANOVA and independent t tests. RESULTS: There was a statistically significant difference between the German plate and screw and all the samples studied on day 6 (P<0.05). Furthermore, a statistically significant difference was observed between both metal samples and both bio-absorbable samples on day 6 and both cell lines (P<0.05). Comparisons between the two groups with each other for both cell lines on the 6th day were statistically significant (P<0.05). CONCLUSION: Our results suggest that that cytotoxicity of biomaterial, from different brands, were not similar and some of the biomaterial showed lower degree of toxicity compared to others and specialist using these products showed be aware of this differences. Our investigation indicates more biocompatibility of bioresorbable plates and screws compared to titanium. In addition our results suggest that biomaterials were not completely neutral.

Hypothesis: A Challenge of Overexpression Zfp521 in Neural Tendency of Derived Dental Pulp Stem Cells.

Neurodegenerative diseases have now become a major challenge, especially in aged societies. Most of the traditional strategies used for treatment of these diseases are untargeted and have little efficiency. Developments in stem cell investigations have given much attention to cell therapy as an alternative concept in the regeneration of neural tissues. Dental pulp stem cells (DPSCs) can be readily obtained by noninvasive procedures and have been shown to possess properties similar to well-known mesenchymal stem cells. Furthermore, based on their neural crest origin, DPSCs are considered to have a good potential to differentiate into neural cells. Zfp521 is a transcription factor that regulates expression of many genes, including ones involved in the neural differentiation process. Therefor based on neural crest origin of the cell and high expression of neural progenitor markers, we speculate that sole overexpression of Zfp521 protein can facilitate differentiation of dental stem cells to neural cells and researchers may find these cells suitable for therapeutic treatment of neurodegenerative diseases.

Comparison of two digestion strategies on characteristics and differentiation potential of human dental pulp stem cells.

OBJECTIVE: This study aimed to compare the behavior of dental pulp stem cells (DPSCs) after isolation using solutions containing either collagenase/dispase or collagenase alone. DESIGN: DPSCs were isolated by two digestion methods (collagenase/dispase or collagenase alone) from human third molars. Immunophenotypic features were confirmed by flow cytometry for cell markers STRO-1, cluster of differentiation (CD) 146, CD45, and collagen type-I. The proliferation potential of cells was evaluated by 5-bromo-2'-deoxyuridine (brdU) incorporation assay, and finally they were assessed for multi-lineage differentiation potential. Data were analyzed using one-way analysis of variance and independent t-tests. RESULTS: DPSCs isolated by either method showed similar levels of STRO-1, CD45, and collagen type-I and similar incorporation of brdU (P > 0.05). However, DPSCs obtained by collagenase I/dispase treatment had significantly higher numbers of CD146+ cells and osteogenic and chondrogenic capacities compared to those obtained by treatment with collagenase I alone (P < 0.05). On the other hand, more STRO-1+/CD164-DPSCs were found in the collagenase alone group with higher adipogenic potential. CONCLUSIONS: Different enzyme solutions gave rise to different populations of DPSCs. Dispase enhanced isolation of CD146+ DPSCs probably by disrupting the basement membranes of blood vessels and releasing DPCSs embedded in the perivascular niche. Furthermore, the differentiation potential of DPSCs was influenced by the change in enzyme solution.

Highly degradable porous melt-derived bioactive glass foam scaffolds for bone regeneration.

A challenge in using bioactive melt-derived glass in bone regeneration is to produce scaffolds with interconnected pores while maintaining the amorphous nature of the glass and its associated bioactivity. Here we introduce a method for creating porous melt-derived bioactive glass foam scaffolds with low silica content and report in vitro and preliminary in vivo data. The gel-cast foaming process was adapted, employing temperature controlled gelation of gelatin, rather than the in situ acrylic polymerisation used previously. To form a 3D construct from melt derived glasses, particles must be fused via thermal processing, termed sintering. The original Bioglass® 45S5 composition crystallises upon sintering, altering its bioactivity, due to the temperature difference between the glass transition temperature and the crystallisation onset being small. Here, we optimised and compared scaffolds from three glass compositions, ICIE16, PSrBG and 13-93, which were selected due to their widened sintering windows. Amorphous scaffolds with modal pore interconnect diameters between 100-150µm and porosities of 75% had compressive strengths of 3.4±0.3MPa, 8.4±0.8MPa and 15.3±1.8MPa, for ICIE16, PSrBG and 13-93 respectively. These porosities and compressive strength values are within the range of cancellous bone, and greater than previously reported foamed scaffolds. Dental pulp stem cells attached to the scaffold surfaces during in vitro culture and were viable. In vivo, the scaffolds were found to regenerate bone in a rabbit model according to X-ray micro tomography imaging. STATEMENT OF SIGNIFICANCE: This manuscript describes a new method for making scaffolds from bioactive glasses using highly bioactive glass compositions. The glass compositions have lower silica content that those that have been previously made into amorphous scaffolds and they have been designed to have similar network connectivity to that of the original (and commercially used) 45S5 Bioglass. The aim was to match Bioglass' bioactivity. The scaffolds retain the amorphous nature of bioactive glass while having an open pore structure and compressive strength similar to porous bone (the original 45S5 Bioglass crystallises during sintering, which can cause reduced bioactivity or instability). The new scaffolds showed unexpectedly rapid bone regeneration in a rabbit model.