Siamak Saifzadeh

Characterisation of ovine bone marrow-derived stromal cells (oBMSC) and evaluation of chondrogenically induced micro-pellets for cartilage tissue repair in vivo

Publisher: Cold Spring Harbor Laboratory

Date: 16-05-2020

DOI: 10.1101/2020.05.15.094847

Abstract: Bone marrow stromal cells (BMSC) show promise in cartilage repair, and sheep are the most common large animal pre-clinical model. The objective of this study was to characterize ovine BMSC (oBMSC) in vitro , and to evaluate the capacity of chondrogenic micro -pellets manufactured from oBMSC or ovine articular chondrocytes (oACh) to repair osteochondral defects in sheep. oBMSC were characterised for surface marker expression using flow cytometry and evaluated for tri-lineage differentiation. oBMSC micro -pellets were manufactured in a microwell platform, and chondrogenesis was compared at 2%, 5%, and 20% O 2 . The capacity of cartilage micro -pellets manufactured from oBMSC or oACh to repair osteochondral defects in adult sheep was evaluated in an 8-week pilot study. Expanded oBMSC were positive for CD44 and CD146 and negative for CD45. The common adipogenic induction medium ingredient, 3-Isobutyl-1-methylxanthine (IBMX) was toxic to oBMSC, but adipogenesis could be restored by excluding IBMX from the medium. BMSC chondrogenesis was optimal in a 2% O 2 atmosphere. Micro -pellets formed from oBMSC or oACh appeared morphologically similar, but hypertrophic genes were elevated in oBMSC micro -pellets. While oACh micro -pellets formed cartilage-like repair tissue in sheep, oBMSC micro -pellets did not. The sensitivity of oBMSC to IBMX highlights species-species differences between oBMSC and hBMSC. Micro -pellets manufactured from oBMSC were not effective in repairing osteochondral defects, while oACh micro -pellets enabled modest repair. While oBMSC can be driven to form cartilage-like tissue in vitro, their effective use in cartilage repair will require mitigation of hypertrophy.

In vitro and in vivo investigation of a zonal microstructured scaffold for osteochondral defect repair

Publisher: Elsevier BV

Date: 07-2022

DOI: 10.1016/J.BIOMATERIALS.2022.121548

Abstract: Articular cartilage is comprised of zones that vary in architecture, extracellular matrix composition, and mechanical properties. Here, we designed and engineered a porous zonal microstructured scaffold from a single biocompatible polymer (poly [ϵ-caprolactone]) using multiple fabrication strategies: electrospinning, spherical porogen leaching, directional freezing, and melt electrowriting. With this approach we mimicked the zonal structure of articular cartilage and produced a stiffness gradient through the scaffold which aligns with the mechanics of the native tissue. Chondrocyte-seeded scaffolds accumulated extracellular matrix including glycosaminoglycans and collagen II over four weeks in vitro. This prompted us to further study the repair efficacy in a skeletally mature porcine model. Two osteochondral lesions were produced in the trochlear groove of 12 animals and repaired using four treatment conditions: (1) microstructured scaffold, (2) chondrocyte seeded microstructured scaffold, (3) MaioRegen™, and (4) empty defect. After 6 months the defect sites were harvested and analyzed using histology, micro computed tomography, and Raman microspectroscopy mapping. Overall, the scaffolds were retained in the defect space, repair quality was repeatable, and there was clear evidence of osteointegration. The repair quality of the microstructured scaffolds was not superior to the control based on histological scoring however, the lower score was biased by the lack of histological staining due to the limited degradation of the implant at 6 months. Longer follow up studies (e.g., 1 yr) will be required to fully evaluate the efficacy of the microstructured scaffold. In conclusion, we found consistent scaffold retention, osteointegration, and prolonged degradation of the microstructured scaffold, which we propose may have beneficial effects for the long-term repair of osteochondral defects.

Additively manufactured biphasic construct loaded with BMP-2 for vertical bone regeneration: A pilot study in rabbit

Publisher: Elsevier BV

Date: 11-2018

DOI: 10.1016/J.MSEC.2018.06.071

Abstract: Vertical bone augmentation of the jaws is required when the height of bone is insufficient at the site of dental implant placement. In this proof of concept study, we investigated the potential of a biphasic polycaprolactone construct combined with a hyaluronic acid based hydrogel loaded with recombinant human bone morphogenetic growth factor-2 (BMP-2) for vertical bone regeneration. The biphasic scaffold consisted of an outer shell manufactured by fused deposition modelling, mimicking native cortical bone and providing mechanical and space maintenance properties essential for bone formation. Within this shell, a 90% porous melt electrospun microfibrous mesh mimicking the architecture of cancellous bone was incorporated in order to facilitate hydrogel loading and subsequent osteogenesis and angiogenesis. The in vitro performances of the biphasic construct demonstrated that BMP-2 was released in a sustained manner over several weeks and that cell viability was maintained in the hydrogel over 21 days. qRT-PCR demonstrated the upregulation of bone markers such as osteopontin, osteocalcin and collagen 1A1 at day 3 and 14 in the constructs loaded with BMP2. In vivo assessment of the biphasic scaffold was performed using a dose of 30 μg of BMP-2 in a rabbit calvarial vertical bone augmentation model. The histology and micro-CT analysis of the elevated space demonstrated that the hydrogel and the presence of BMP-2 enabled bone formation. However, this was limited to the immediate vicinity of the calvarial bone. The amount of newly formed bone was relatively small which was likely due to poor vascularisation of the extraskeletal space. The utilisation of this biomimetic biphasic construct with excellent space maintenance properties can be of interest in dentistry although the in vivo model requires refinement to demonstrated appropriate efficacy.

3D-Printed Medical-Grade Polycaprolactone (mPCL) Scaffold for the Surgical Treatment of Vaginal Prolapse and Abdominal Hernias

Publisher: MDPI AG

Date: 24-10-2023

DOI: 10.3390/BIOENGINEERING10111242

Convergence of scaffold-guided bone regeneration principles and microvascular tissue transfer surgery

Publisher: American Association for the Advancement of Science (AAAS)

Date: 05-05-2023

DOI: 10.1126/SCIADV.ADD6071

Abstract: A preclinical evaluation using a regenerative medicine methodology comprising an additively manufactured medical-grade ε-polycaprolactone β-tricalcium phosphate (mPCL-TCP) scaffold with a corticoperiosteal flap was undertaken in eight sheep with a tibial critical-size segmental bone defect (9.5 cm 3 , M size) using the regenerative matching axial vascularization (RMAV) approach. Biomechanical, radiological, histological, and immunohistochemical analysis confirmed functional bone regeneration comparable to a clinical gold standard control (autologous bone graft) and was superior to a scaffold control group (mPCL-TCP only). Affirmative bone regeneration results from a pilot study using an XL size defect volume (19 cm 3 ) subsequently supported clinical translation. A 27-year-old adult male underwent reconstruction of a 36-cm near-total intercalary tibial defect secondary to osteomyelitis using the RMAV approach. Robust bone regeneration led to complete independent weight bearing within 24 months. This article demonstrates the widely advocated and seldomly accomplished concept of “bench-to-bedside” research and has weighty implications for reconstructive surgery and regenerative medicine more generally.

A preclinical large-animal model for the assessment of critical-size load-bearing bone defect reconstruction

Publisher: Springer Science and Business Media LLC

Date: 14-02-2020

DOI: 10.1038/S41596-019-0271-2

The adhesion-GPCR BAI3, a gene linked to psychiatric disorders, regulates dendrite morphogenesis in neurons

Publisher: Springer Science and Business Media LLC

Date: 30-04-2013

DOI: 10.1038/MP.2013.46

CNRS Délégation Alsace

Location: France

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CNRS Délégation Paris B

Location: France

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Ecole Normale Supérieure Département De Biologie

Location: France

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Urmia University

Location: Iran (Islamic Republic of)

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Shiraz University School Of Veterinary Medicine

Location: Iran (Islamic Republic of)

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Institute Of Health And Biomedical Innovation

Location: Australia

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Linkage Projects - Grant ID: LP100200084

Start Date: 09-2011

End Date: 12-2013

Amount: $304,000.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP110200082

Start Date: 06-2012

End Date: 12-2015

Amount: $291,000.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP0991527

Start Date: 06-2010

End Date: 12-2013

Amount: $260,000.00

Funder: Australian Research Council

Industrial Transformation Training Centres - Grant ID: IC180100008

Start Date: 07-2019

End Date: 06-2025

Amount: $3,981,223.00

Funder: Australian Research Council

Industrial Transformation Training Centres - Grant ID: IC190100026

Start Date: 01-2021

End Date: 11-2027

Amount: $4,969,663.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP120104611

Start Date: 2012

End Date: 12-2015

Amount: $270,000.00

Funder: Australian Research Council

Development And Characterization Of A Technology Platform To Study The Mechanisms Of Scaffold/Bone Morphogenic Proteins (BMP) Augmented Large Segmental Bone Healing

Start Date: 2009

End Date: 2012

Funder: Australian Research Council

Bone Tissue Engineering Using Innovative Tubular Dual-layered Nanofiber Meshes

Start Date: 2010

End Date: 2013

Funder: Australian Research Council

The Development Of New Scaffolds For Bone Repair Comprising Polycaprolactone And Strontium-substituted Bioactive Glasses

Start Date: 2011

End Date: 2014

Funder: Australian Research Council

Convergence Of Biomaterials And Immunology: A Technology Platform For Delayed Burst Release Of Vaccines

Start Date: 2012

End Date: 2014

Funder: Australian Research Council