scholarly journals Inclusion of a 3D-printed Hyperelastic bone mesh improves mechanical and osteogenic performance of a mineralized collagen scaffold

2020 ◽  
Author(s):  
Marley J. Dewey ◽  
Andrey V. Nosatov ◽  
Kiran Subedi ◽  
Ramille Shah ◽  
Adam Jakus ◽  
...  
Keyword(s):  
Mechanical Performance ◽  
Negative Impact ◽  
Collagen Scaffold ◽  
Collagen Scaffolds ◽  
Shape Fitting ◽  
Cell Processes ◽  
3D Printed ◽  
Future Work ◽  
Mineralized Collagen

ABSTRACTRegenerative repair of craniomaxillofacial bone injuries is challenging due to both the large size and irregular shape of many defects. Mineralized collagen scaffolds have previously been shown to be a promising biomaterial implant to accelerate craniofacial bone regeneration in vivo. Here we describe inclusion of a 3D-printed polymer or ceramic-based mesh into a mineralized collagen scaffold to improve mechanical and biological activity. Mineralized collagen scaffolds were reinforced with 3D-printed Fluffy-PLG (ultraporous polylactide-co-glycolide co-polymer) or Hyperelastic Bone (90wt% calcium phosphate in PLG) meshes. We show degradation byproducts and acidic release from the printed structures have limited negative impact on the viability of mesenchymal stem cells. Further, inclusion of a mesh formed from Hyperelastic Bone generates a reinforced composite with significantly improved mechanical performance (elastic modulus, push-out strength). Composites formed from the mineralized collagen scaffold and either Hyperelastic Bone or Fluffy-PLG reinforcement both supported human bone-marrow derived mesenchymal stem cell osteogenesis and new bone formation. Strikingly, composites reinforced with Hyperelastic Bone mesh elicited significantly increased secretion of osteoprotegerin, a soluble glycoprotein and endogenous inhibitor of osteoclast activity. These results suggest that architectured meshes can be integrated into collagen scaffolds to boost mechanical performance and actively instruct cell processes that aid osteogenicity; specifically, secretion of a factor crucial to inhibiting osteoclast-mediated bone resorption. Future work will focus on further adapting the polymer mesh architecture to confer improved shape-fitting capacity as well as to investigate the role of polymer reinforcement on MSC-osteoclast interactions as a means to increase regenerative potential.

scholarly journals Repair of critical-size porcine craniofacial bone defects using a collagen-polycaprolactone composite biomaterial

2021 ◽  
Author(s):  
Marley J Dewey ◽  
Derek J Milner ◽  
Daniel Weisgerber ◽  
Colleen Flanagan ◽  
Marcello Rubessa ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Fibrous Tissue ◽  
Bone Defects ◽  
Large Animal ◽  
Collagen Scaffolds ◽  
Shape Fitting ◽  
Large Animal Models ◽  
3D Printed ◽  
Mineralized Collagen

Regenerative medicine approaches for massive craniomaxillofacial bone defects face challenges associated with the scale of missing bone, the need for rapid graft-defect integration, and challenges related to inflammation and infection. Mineralized collagen scaffolds have been shown to promote mesenchymal stem cell osteogenesis due to their porous nature and material properties, but are mechanically weak, limiting surgical practicality. Previously, these scaffolds were combined with 3D-printed polycaprolactone mesh to form a scaffold-mesh composite to increase strength and promote bone formation in sub-critical sized porcine ramus defects. Here, we compare the performance of mineralized collagen-polycaprolactone composites to the polycaprolactone mesh in a critical-sized porcine ramus defect model. While there were no differences in overall healing response between groups, our data demonstrated broadly variable metrics of healing regarding new bone infiltration and fibrous tissue formation. Abscesses were present surrounding some implants and polycaprolactone polymer was still present after 9-10 months of implantation. Overall, while there was limited successful healing, with 2 of 22 implants showed substantial levels of bone regeneration, and others demonstrating some form of new bone formation, the results suggest targeted improvements to improve repair of large animal models to more accurately represent craniomaxillofacial bone healing. Notably, strategies to increase osteogenesis throughout the implant, modulate the immune system to support repair, and employ shape-fitting tactics to avoid implant micromotion and resultant fibrosis. Improvements to the mineralized collagen scaffolds involve changes in pore size and shape to increase cell migration and osteogenesis and inclusion or delivery of factors to aid vascular ingrowth and bone regeneration.

Abstract 17070: Engineering a Novel Ex Vivo Heart Simulator for Biomechanical Analysis of the Aortomitral Junction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Matthew H Park ◽  
Annabel Imbrie-moore ◽  
Yuanjia Zhu ◽  
Hanjay Wang ◽  
Michael J Paulsen ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Ex Vivo ◽  
Clinical Care ◽  
Biomechanical Analysis ◽  
Future Experimentation ◽  
3D Printed ◽  
Biomechanical Changes ◽  
Predictive Risk ◽  
Future Work

Introduction: Advances in ex vivo heart simulation have enabled the study of valvular biomechanics, disease pathologies, and repair strategies. However, these simulators test the valves in isolation, which does not fully replicate in vivo physiology. We hypothesize that by engineering a simulator that preserves the aortomitral junction, we can better recreate pathophysiologies such as systolic anterior motion (SAM). Here, we present a new heart simulator that preserves and manipulates the native aortomitral physiology. Methods: Our simulator is comprised of three subsystems: the ventricular chamber, atrial chamber, and aortic chamber (Fig A, B). The heart is excised at the apex to preserve the papillary muscles, and the left ventricle, atrial cuff, and aorta are fixed to their respective chambers via hemostatic suturing to 3D-printed elastomeric rings. The chambers are equipped with pressure and flow sensors, and a linear piston pump generates physiologic pressures and flows. The atrial and aortic chambers are mounted on 5-degree-of-freedom arms. To demonstrate system function, we manipulated the aortomitral angle and measured aortic cardiac output. Results: In our testing, we evaluated two unique configurations of an explanted porcine heart, of which the aortomitral angles spanned the SAM predictive risk threshold of <120° (Fig C, D). From the flow readings, we measured a 36% reduction in aortic cardiac output upon decreasing the aortomitral angle by 25°. Conclusions: This work highlights the design and development of an ex vivo heart simulator capable of modeling native aortomitral physiology. Our results point to a clear direction for future experimentation, particularly evaluating the biomechanical changes of the heart based on the aortomitral angle. Future work will utilize this platform to create new models and repair techniques to ultimately improve clinical care of valvular pathologies.

scholarly journals Dendrimer Functionalized Metal Oxide Nanoparticle mediated Self-Assembled Collagen Scaffold for Skin Regenerative Application: Function of Metal in Metal oxides

2021 ◽  
Author(s):  
KJ Sree ◽  
Mohan Vedhanayagam ◽  
Balachandran Unni Nair ◽  
Anandasadagopan Suresh kumar
Keyword(s):  
Metal Oxide ◽  
Mechanical Strength ◽  
Cell Viability ◽  
Metal Oxide Nanoparticles ◽  
Collagen Scaffold ◽  
Albino Rats ◽  
Oxide Nanoparticles ◽  
Collagen Scaffolds ◽  
Assembly Method

Abstract Functionalized metal oxide nanoparticles cross-linked collagen scaffolds are widely used in skin regenerative applications because of their enhanced physico-chemical and biocompatibility properties. From the safety clinical trials point of view, there are no reports that have compared the effects of functionalized metal oxide nanoparticles mediated collagen scaffolds for in-vivo skin regenerative applications. In this work, Triethoxysilane - Poly (amido amine) dendrimer generation 3 (TES-PAMAM -G3 or G3) functionalized spherical shape metal oxide nanoparticles (MO NPs: ZnO, TiO2, Fe3O4, CeO2, and SiO2, Size: 12 -25 nm) cross-linked collagen scaffolds were prepared by using a self-assembly method. Triple helical conformation, pore size, mechanical strength and in-vitro cell viability of MO-TES-PAMAM-G3- collagen scaffolds were studied through different methods. The in-vivo skin regenerative proficiency of MO-TES-PAMAM-G3- collagen scaffolds were analysed by implanting the scaffold on wounds in Wistar Albino rats. The results demonstrated that MO-TES-PAMAM-G3- collagen scaffold showed superior skin regeneration properties than other scaffolds. The skin regenerative efficiency of MO NPs followed order: ZnO> TiO2> CeO2> SiO2> Fe3O4 NPs. This result can be attributed to higher mechanical strength, cell –viability and better antibacterial activity of ZnO-TES-PAMAM-G3-collagen scaffold lead to accelerate the skin regenerative properties in comparison to other metal oxide based collagen scaffolds.

The Tissue Engineering Approach to Ligament Reconstruction

1993 ◽  
Vol 331 ◽  
Author(s):  
Michael G. Dunn ◽  
J. B. Liesch ◽  
M. L. Tiku ◽  
S. H. Maxian ◽  
J. P. Zawadsky
Keyword(s):  
Acl Reconstruction ◽  
Patellar Tendon ◽  
Cruciate Ligament ◽  
Collagen Scaffold ◽  
In Vivo Studies ◽  
Collagen Scaffolds ◽  
Tissue Engineering Approach ◽  
Anterior Cruciate

AbstractPrevious studies in our laboratory showed that acellular collagen scaffold implants induce tissue ingrowth and perform similar to autografts following reconstruction of rabbit Achilles tendon or anterior cruciate ligament (ACL). We chronologically review these and related studies, and report preliminary development of fibroblast-seeded collagen scaffolds potentially useful for ACL reconstruction. The ‘healing potential’ of fibroblasts was measured within collagen scaffolds in vitro, as a function of fibroblast source. Aligned collagen scaffolds were seeded with fibroblasts from rabbit ACL, synovium, patellar tendon, or skin. Fibroblast viability, adherence, spreading, proliferation, and protein and collagen deposition were measured on collagen scaffolds. The fibroblasts attached to the scaffolds, and spread along the long axis of the collagen fibers. ACL fibroblasts adhered better than other fibroblast types; however, the ACL fibroblasts proliferated at the slowest rate. Patellar tendon fibroblasts proliferated at the most rapid rate. All four of the fibroblast types secreted protein and collagen within the collagen scaffolds.Preliminary in vivo studies suggest that fibroblasts seeded onto collagen scaffolds can remain viable following reimplantation into the donor rabbit. Ongoing studies will elucidate the role of autogenous seeded fibroblasts in neoligament formation/remodeling. These ‘ligament analogs’ are potentially useful for clinical ACL reconstruction: fibroblasts would be obtained from biopsy, cultured, seeded onto a collagen scaffold, and implanted as an ACL substitute into the same patient.

scholarly journals Inclusion of a 3d-Printed Hyperelastic Bone Mesh Improves Mechanical and Osteogenic Performance of a Mineralized Collagen Scaffold

2020 ◽  
Author(s):  
Marley J. Dewey ◽  
Andrey V. Nosatov ◽  
Kiran Subedi ◽  
Ramille Shah ◽  
Adam Jakus ◽  
...  
Keyword(s):  
Collagen Scaffold ◽  
3D Printed ◽  
Mineralized Collagen

scholarly journals Inclusion of a 3D-printed Hyperelastic Bone mesh improves mechanical and osteogenic performance of a mineralized collagen scaffold

2020 ◽  
Author(s):  
Marley J. Dewey ◽  
Andrey V. Nosatov ◽  
Kiran Subedi ◽  
Ramille Shah ◽  
Adam Jakus ◽  
...  
Keyword(s):  
Collagen Scaffold ◽  
3D Printed ◽  
Mineralized Collagen

scholarly journals Anisotropic mineralized collagen scaffolds accelerate osteogenic response in a glycosaminoglycan-dependent fashion

2020 ◽  
Author(s):  
Marley J. Dewey ◽  
Andrey V. Nosatov ◽  
Kiran Subedi ◽  
Brendan Harley
Keyword(s):  
Cell Activity ◽  
Collagen Scaffold ◽  
Human Mesenchymal Stem Cell ◽  
Collagen Scaffolds ◽  
Age Related ◽  
Heparin Sulfate ◽  
Osteogenic Response ◽  
Mineralized Collagen

ABSTRACTRegeneration of critically-sized craniofacial bone defects requires a template to promote cell activity and bone remodeling. However, induced regeneration becomes more challenging with increasing defect size. Methods of repair using allografts and autografts have inconsistent results, attributed to age-related regenerative capabilities of bone. We are developing a mineralized collagen scaffold to promote craniomaxillofacial bone regeneration as an alternative to repair. Here, we hypothesize modifying the pore anisotropy and glycosaminoglycan content of the scaffold will improve cell migration, viability, and subsequent bone formation. Using anisotropic and isotropic scaffold variants, we test the role of pore orientation on human mesenchymal stem cell (MSC) activity. We subsequently explore the role of glycosaminoglycan content, notably chondroitin-6-sulfate, chondroitin-4-sulfate, and heparin sulfate on mineralization. We find that while short term MSC migration and activity was not affected by pore orientation, increased bone mineral synthesis was observed in anisotropic scaffolds. Further, while scaffold glycosaminoglycan content did not impact cell viability, heparin sulfate and chondroitin-6-sulfate containing variants increased mineral formation at the late stage of in vitro culture, respectively. Overall, these findings show scaffold microstructural and proteoglycan modifications represent a powerful tool to improve MSC osteogenic activity.

In vivo Evaluation of a Collagen Scaffold Preconditioned with Adipose-derived Mesenchymal Stem Cells Used for Bone Regeneration A histological study

2018 ◽  
Vol 55 (4) ◽  
pp. 691-695
Author(s):  
Tudor Sorin Pop ◽  
Anca Maria Pop ◽  
Alina Dia Trambitas Miron ◽  
Klara Brinzaniuc ◽  
Simona Gurzu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Histological Study ◽  
Collagen Scaffold ◽  
Bone Defects ◽  
Collagen Scaffolds ◽  
In Vivo Evaluation ◽  
Calvarial Bone ◽  
Bone Apposition

The use of collagen scaffolds and stem cells for obtaining a tissue-engineering complex has been an important concept in promoting repair and regeneration of the bone tissue. Such units represent important steps in the development of an ideal scaffold-cell complex that would sustain new bone apposition. The aim of our study was to perform a histologic evaluation of the healing of critical-sized bone defects, using a biologic collagen scaffold with adipose-derived mesenchymal stem cells, in comparison to negative controls created in the adjacent bone. We used 16 Wistar rats and according to the study design 2 calvarial bone defects were created in each animal, one was filled with collagen seeded with adipose-derived stem cells and the other one was considered negative control. During the following month, at weekly intervals, the animals were euthanized and the specimens from bone defects were histologically evaluated. The results showed that these scaffolds were highly biocompatible as only moderate inflammation no rejection reactions were observed. Furthermore, the first signs of osseous healing appeared after two weeks accompanied by angiogenesis. Collagen scaffolds seeded with adipose-derived mesenchymal stem cells can be considered a promising treatment option in bone regeneration of large defects.

Sign in / Sign up

Export Citation Format

Share Document