I-Optimal Design of Hierarchical 3D Scaffolds Produced by Combining Additive Manufacturing and Thermally Induced Phase Separation

Yousefi, Azizeh‐Mitra; Liu, Junyi; Sheppard, R.; Koo, Songmi; Silverstein, Joshua; Zhang, Houcheng; James, Paul F.

doi:10.1021/acsabm.8b00534

Cited by 18 publications

(20 citation statements)

References 66 publications

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“…The interconnected channels produced by 3DP provided an ideal environment to guide bone ingrowth. The matrix surrounding the channels had micropores generated by TIPS, where the pore size can be controlled by manipulating the experimental factors . These scaffolds supported the growth of MC3T3‐E1 osteoblastic cells in vitro .…”

Section: Discussionmentioning

confidence: 99%

I‐Optimal design of poly(lactic‐co‐glycolic) acid/hydroxyapatite three‐dimensional scaffolds produced by thermally induced phase separation

Liu

Zhang

James

et al. 2019

Polymer Engineering & Sci

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In bone tissue engineering, three‐dimensional (3D) scaffolds are often designed to have adequate modulus while taking into consideration the requirement for a highly porous network for cell seeding and tissue growth. This article presents the design optimization of 3D scaffolds made of poly(lactic‐co‐glycolic) acid (PLGA) and nanohydroxyapatite (nHA), produced by thermally induced phase separation (TIPS). Slow cooling at a rate of 1°C/min enabled a uniform temperature and produced porous scaffolds with a relatively uniform pore size. An I‐optimal design of experiments (DoE) with 18 experimental runs was used to relate four responses (scaffold thickness, density, porosity, and modulus) to three experimental factors, namely the TIPS temperature (−20, −10, and 0°C), PLGA concentration (7%, 10%, and 13% w/v), and nHA content (0%, 15%, and 30% w/w). The response surface analysis using JMP® software predicted a temperature of −18.3°C, a PLGA concentration of 10.3% w/v, and a nHA content of 30% w/w to achieve a thickness of 3 mm, a porosity of 83%, and a modulus of ~4 MPa. The set of validation scaffolds prepared using the predicted factor levels had a thickness of 3.05 ± 0.37 mm, a porosity of 86.8 ± 0.9%, and a modulus of 3.57 ± 2.28 MPa. POLYM. ENG. SCI., 59:1146–1157 2019. © 2019 Society of Plastics Engineers

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Section: Discussionmentioning

confidence: 99%

I‐Optimal design of poly(lactic‐co‐glycolic) acid/hydroxyapatite three‐dimensional scaffolds produced by thermally induced phase separation

Liu

Zhang

James

et al. 2019

Polymer Engineering & Sci

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“…Various synthetic and natural biomaterials have been widely investigated as scaffolding materials in tissue engineering fields [ 11 ]. Among them, aliphatic polyesters such as polylactide (PLA) [ 12 , 13 , 14 ], polyglycolide (PGA) [ 15 , 16 ], polycaprolactone (PCL) [ 17 , 18 ] and their copolymers like poly(lactide- co -glycolide) (PLGA) [ 19 , 20 , 21 , 22 ], poly( l -lactide- co -caprolactone) (PLCL) [ 23 ], poly-(glycolide- co -caprolactone (PGCL) [ 24 ] and poly( l -lactide- co -glycolide- co -ε-caprolactone) (PLLGC) [ 25 ] have received significant scientific attention due to their good biocompatibility and biodegradability. Furthermore, most of them have been approved by the Food and Drug Administration (FDA) for certain clinical applications [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

“…This method allows obtaining polymeric foams with porosity over 95% [ 57 ] and pore diameters from ~1 to 100 µm [ 53 ]. Numerous innovations in this area, including combination of TIPS with other fabrication techniques such as electrospinning [ 58 , 59 ], porogen leaching [ 60 , 61 , 62 ], 3D printing [ 21 , 22 , 63 ], modification of the solvent removal procedure [ 14 , 64 ] or variations in TIPS parameters [ 14 , 21 , 46 , 51 , 64 , 65 ] has been reported in literature.…”

Section: Introductionmentioning

confidence: 99%

Recent Progress on Biodegradable Tissue Engineering Scaffolds Prepared by Thermally-Induced Phase Separation (TIPS)

Zeinali

Valle

Torras

et al. 2021

IJMS

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Porous biodegradable scaffolds provide a physical substrate for cells allowing them to attach, proliferate and guide the formation of new tissues. A variety of techniques have been developed to fabricate tissue engineering (TE) scaffolds, among them the most relevant is the thermally-induced phase separation (TIPS). This technique has been widely used in recent years to fabricate three-dimensional (3D) TE scaffolds. Low production cost, simple experimental procedure and easy processability together with the capability to produce highly porous scaffolds with controllable architecture justify the popularity of TIPS. This paper provides a general overview of the TIPS methodology applied for the preparation of 3D porous TE scaffolds. The recent advances in the fabrication of porous scaffolds through this technique, in terms of technology and material selection, have been reviewed. In addition, how properties can be effectively modified to serve as ideal substrates for specific target cells has been specifically addressed. Additionally, examples are offered with respect to changes of TIPS procedure parameters, the combination of TIPS with other techniques and innovations in polymer or filler selection.

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“…Native tissues have high demands for mass transport exchanging nutrients and oxygen for metabolic waste [1 , 2] . As tissue develops these requirements are met primarily by blood perfusion through large multi-centimetre to multi-micron scale vessel networks [3] .…”

Section: Introductionmentioning

confidence: 99%

“…Various approaches have been developed to create perfusable vascularized tissues including layer-by-layer assembly [6] , [7] , [8] and recently complex additive manufacturing/3D printing/Bio-printing technologies [1 , 2 , 9] . Layer-by-layer technologies (which moulds a channel into one layer such that bonding of the second flat layer creates a vessel [7] ) is an iterative process and can create thick, multi-layered tissues.…”

Section: Introductionmentioning

confidence: 99%

Human-scale tissues with patterned vascular networks by additive manufacturing of sacrificial sugar-protein composites

et al. 2020

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Combating necrosis, by supplying nutrients and removing waste, presents the major challenge for engineering large three-dimensional (3D) tissues. Previous elegant work used 3D printing with carbohydrate glass as a cytocompatible sacrificial template to create complex engineered tissues with vascular networks (Miller et al. 2012, Nature Materials). The fragile nature of this material compounded with the technical complexity needed to create high-resolution structures led us to create a flexible sugar-protein composite, termed Gelatin-sucrose matrix (GSM), to achieve a more robust and applicable material. Here we developed a low-range (25–37˚C) temperature sensitive formulation that can be moulded with micron-resolution features or cast during 3D printing to produce complex flexible filament networks forming sacrificial vessels. Using the temperature-sensitivity, we could control filament degeneration meaning GSM can be used with a variety of matrices and crosslinking strategies. Furthermore by incorporation of biocompatible crosslinkers into GSM directly, we could create thin endothelialized vessel walls and generate patterned tissues containing multiple matrices and cell-types. We also demonstrated that perfused vascular channels sustain metabolic function of a variety of cell-types including primary human cells. Importantly, we were able to construct vascularized human noses which otherwise would have been necrotic. Our material can now be exploited to create human-scale tissues for regenerative medicine applications. Statement of Significance Authentic and engineered tissues have demands for mass transport, exchanging nutrients and oxygen, and therefore require vascularization to retain viability and inhibit necrosis. Basic vascular networks must be included within engineered tissues intrinsically. Yet, this has been unachievable in physiologically-sized constructs with tissue-like cell densities until recently. Sacrificial moulding is an alternative in which networks of rigid lattices of filaments are created to prevent subsequent matrix ingress. Our study describes a biocompatible sacrificial sugar-protein formulation; GSM, made from mixtures of inexpensive and readily available bio-grade materials. GSM can be cast/moulded or bioprinted as sacrificial filaments that can rapidly dissolve in an aqueous environment temperature-sensitively. GSM material can be used to engineer viable and vascularized human-scale tissues for regenerative medicine applications.

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I-Optimal Design of Hierarchical 3D Scaffolds Produced by Combining Additive Manufacturing and Thermally Induced Phase Separation

Cited by 18 publications

References 66 publications

I‐Optimal design of poly(lactic‐co‐glycolic) acid/hydroxyapatite three‐dimensional scaffolds produced by thermally induced phase separation

I‐Optimal design of poly(lactic‐co‐glycolic) acid/hydroxyapatite three‐dimensional scaffolds produced by thermally induced phase separation

Recent Progress on Biodegradable Tissue Engineering Scaffolds Prepared by Thermally-Induced Phase Separation (TIPS)

Human-scale tissues with patterned vascular networks by additive manufacturing of sacrificial sugar-protein composites

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