Sustained delivery of growth factors with high loading efficiency in a layer by layer assembly

Damanik, Febriyani; Brunelli, Marzia; Pastorino, Laura; Ruggiero, Carmelina; Blitterswijk, Clemens van; Rotmans, Joris I.; Moroni, Lorenzo

doi:10.1039/c9bm00979e

Cited by 24 publications

(20 citation statements)

References 67 publications

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“…A longer adsorption time was needed for the deposition of K 3 PA molecule compared with ALG, showing that the binding and arrangement of K 3 PA was slow. Although not reported in this study, multiple GFs could be loaded during multi-layer build-up for sequential GF co-delivery [60]. Using the negatively charged synthetic polymer poly(sodium 4-styrenesulfonate) (PSS) and a positively charged PA (palmitoyl-V 3 A 3 K 3 -NH 2 ), a hybrid supramolecular hydrogel was reported recently ( Figure 5) [61].…”

Section: Multi-component Hydrogelsmentioning

confidence: 79%

Supramolecular Hydrogels for Protein Delivery in Tissue Engineering

Lyu

Azevedo

2021

Molecules

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Therapeutic proteins, such as growth factors (GFs), have been used in tissue engineering (TE) approaches for their ability to provide signals to cells and orchestrate the formation of functional tissue. However, to be effective and minimize off-target effects, GFs should be delivered at the target site with temporal control. In addition, protein drugs are typically sensitive water soluble macromolecules with delicate structure. As such, hydrogels, containing large amounts of water, provide a compatible environment for the direct incorporation of proteins within the hydrogel network, while their release rate can be tuned by engineering the network chemistry and density. Being formed by transient crosslinks, afforded by non-covalent interactions, supramolecular hydrogels offer important advantages for protein delivery applications. This review describes various types of supramolecular hydrogels using a repertoire of diverse building blocks, their use for protein delivery and their further application in TE contexts. By reviewing the recent literature on this topic, the merits of supramolecular hydrogels are highlighted as well as their limitations, with high expectations for new advances they will provide for TE in the near future.

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Section: Multi-component Hydrogelsmentioning

confidence: 79%

Supramolecular Hydrogels for Protein Delivery in Tissue Engineering

Lyu

Azevedo

2021

Molecules

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“…Single GF incorporation in the sequence of (PEI/PSS) 2 /(GF/HEP) 4 PEI/PSS/PEI in which GF represents TGF‐β1, PDGF‐ ββ , and IGF‐1 were similarly done as the final optimised procedure previously described. [ 20 ] Table 1 summarizes the LbL conditions and nomenclature used throughout the study. Briefly, polyethylenimine (PEI, M w = 25 000) and poly(styrenesulfonate) (PSS, M w = 70 000) were dissolved at 2 mg mL −1 in MilliQ water at a pH 3 and 10, respectively; while Heparin (HEP) at 1 mg mL −1 in NaCl 0.15 m at pH 9.…”

Section: Methodsmentioning

confidence: 99%

“…We showed controlled release, while still maintaining their biological functionalities. [20] The complex cellular process of migration, proliferation, differentiation and protein secretion are typically dependant on the presence of specific spatio-temporal distribution of multiple GFs. Numerous studies have encouraged the combination of GFs sequentially released over single delivery.…”

Section: Introductionmentioning

confidence: 99%

Control Delivery of Multiple Growth Factors to Actively Steer Differentiation and Extracellular Matrix Protein Production

et al. 2021

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In tissue engineering, biomaterials have been used to steer the host response. This determines the outcome of tissue regeneration, which is modulated by multiple growth factors (GFs). Hence, a sustainable delivery system for GFs is necessary to control tissue regeneration actively. A delivery technique of single and multiple GF combinations, using a layer‐by‐layer (LBL) procedure to improve tissue remodeling, is developed. TGF‐β1, PDGF‐ββ, and IGF‐1 are incorporated on tailor‐made polymeric rods, which could be used as a tool for potential tissue engineering applications, such as templates to induce the formation of in situ tissue engineered blood vessels (TEBVs). Cell response is analyzed in vitro using rat and human dermal fibroblasts for cellular proliferation, fibroblast differentiation, and extracellular matrix (ECM) protein synthesis. Results revealed a higher loading efficiency and control release of GFs incorporated on chloroform and oxygen plasma‐activated (COX) rods. Single PDGF‐ββ and IGF‐1 release, and dual release with TGF‐β1 from COX rods, showed higher cell proliferation when compared to COX rods alone. A substantial increase in α‐smooth muscle actin (α‐SMA) is also observed in GF releasing COX rods, with TGF‐β1 COX rods providing the most pronounced differentiation. A significant increase in collagen and elastin synthesis is observed on all GF releasing COX rods compared to control, with COX rods releasing TGF‐β1 and IGF‐1 providing the highest secretion. TGF‐β1 and IGF‐1 releasing COX rods induced higher Glycosaminoglycan (GAG)/DNA amounts than the other GF releasing COX rods. As PDGF‐ββ and TGF‐β1/PDGF‐ββ COX rods displayed the highest fibroblast attachment, these rods provided the highest total collagen and elastin production. The attractive results from efficiently incorporating single and multiple GFs on COX rods and their sustainable release to steer cellular behavior suggest a promising route to enrich the formation of in situ engineered tissues.

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“…It has been commonly used to modify porous scaffolds with a flexible structure for controlled delivery of growth factors, as it shows good performance in avoiding growth factors loss of function and sequestering the high concentration of growth factors under mild aqueous conditions. 108 For this assembly process, typical hydrogen bonding, covalent interactions or electrostatic interactions are commonly used. By assembling alternating layers of sodium poly styrene sulfonate (PSS) and poly allylamine (PAH) onto planar surfaces, the polymeric multilayer capsules store growth factors and maintain their biological activity.…”

Section: Layer By Layer Assemblymentioning

confidence: 99%

“…109 In addition, dextran sulphate and heparin were chosen to be the counter polyelectrolytes in order to better protect growth factor ligands. 108 The morphology of the film prepared by LBL assembly is controllable and can also be compounded with other carriers. During the process, through adjusting the inherent properties of the polyelectrolyte multilayers, the growth factor release behavior can be regulated.…”

Section: Layer By Layer Assemblymentioning

confidence: 99%

<p>Growth Factor and Its Polymer Scaffold-Based Delivery System for Cartilage Tissue Engineering</p>

Chen¹,

Liu²,

Guan³

et al. 2020

IJN

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The development of biomaterials, stem cells and bioactive factors has led to cartilage tissue engineering becoming a promising tactic to repair cartilage defects. Various polymer three-dimensional scaffolds that provide an extracellular matrix (ECM) mimicking environment play an important role in promoting cartilage regeneration. In addition, numerous growth factors have been found in the regenerative process. However, it has been elucidated that the uncontrolled delivery of these factors cannot fully exert regenerative potential and can also elicit undesired side effects. Considering the complexity of the ECM, neither scaffolds nor growth factors can independently obtain successful outcomes in cartilage tissue engineering. Therefore, collectively, an appropriate combination of growth factors and scaffolds have great potential to promote cartilage repair effectively; this approach has become an area of considerable interest in recent investigations. Of late, an increasing trend was observed in cartilage tissue engineering towards this combination to develop a controlled delivery system that provides adequate physical support for neo-cartilage formation and also enables spatiotemporally delivery of growth factors to precisely and fully exert their chondrogenic potential. This review will discuss the role of polymer scaffolds and various growth factors involved in cartilage tissue engineering. Several growth factor delivery strategies based on the polymer scaffolds will also be discussed, with examples from recent studies highlighting the importance of spatiotemporal strategies for the controlled delivery of single or multiple growth factors in cartilage tissue engineering applications.

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Sustained delivery of growth factors with high loading efficiency in a layer by layer assembly

Abstract: Layer by layer (LBL) assembly garnered considerable interest due to its ability to generate multifunctional films with high tunability and versatility in terms of substrates and polyelectrolytes, allowing the option to use complex devices and drugs.

Cited by 24 publications

References 67 publications

Supramolecular Hydrogels for Protein Delivery in Tissue Engineering

Supramolecular Hydrogels for Protein Delivery in Tissue Engineering

Control Delivery of Multiple Growth Factors to Actively Steer Differentiation and Extracellular Matrix Protein Production

<p>Growth Factor and Its Polymer Scaffold-Based Delivery System for Cartilage Tissue Engineering</p>

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