Porous Hyaluronic Acid Research Articles

Injectable Amphipathic Artesunate Prodrug‐Hydrogel Microsphere as Gene/Drug Nano‐Microplex for Rheumatoid Arthritis Therapy

AbstractArtemisinin and its derivatives (artemisinins) are first‐line chemotherapeutic agents of lethal malaria, which also showed tremendous value in many other diseases including chronic inflammation. Unfortunately, almost all artemisinins are rapid‐acting medicines with an extremely short half‐life in vivo, which significantly limits their clinical application for these new adaptation diseases. In this study, a locally injectable long‐acting gene/artemisinin co‐delivery nano‐microplex consisting of a biodegradable hyaluronic acid (HA) microsphere and releasable gene/artemisinin co‐delivery nano‐lipoplex is developed first, to obtain an improved efficacy for rheumatoid arthritis (RA). Briefly, a cationic multicomponent drug‐embedded liposome with pharmacological activity is first reported based on two novel artemisinin derivatives (dAPC and dACC), which possess mimic phospholipids and cationic lipids, respectively. A cationic artemisinin‐embedded lipoplex is first reported as a medicative gene carrier here. An in situ injectable TNF‐α siRNA/artemisinin co‐delivery nano‐microplex (MTAsi@MG) is further prepared by immobilization of TNF‐α siRNA/lipoplex on porous microfluidic HA microspheres. Using this nano‐microplex for intra‐articular injection, the sustaining activity of gene therapy and artemisinin efficacy for RA long‐term treatment is first realized. Undoubtedly, this intra‐articular injectable TNF‐α siRNA/artemisinin co‐delivery nano‐microplex based on dAPC/dACC lipoplex and microfluidic microspheres would be one of the most potent gene/drug co‐delivery systems for RA therapy.

Cartilage tissue engineering by extrusion bioprinting utilizing porous hyaluronic acid microgel bioinks

3D bioprinting offers an excellent opportunity to provide tissue-engineered cartilage to microtia patients. However, hydrogel-based bioinks are hindered by their dense and cell-restrictive environment, impairing tissue development and ultimately leading to mechanical failure of large scaffolds in vivo. Granular hydrogels, made of annealed microgels, offer a superior alternative to conventional bioinks, with their improved porosity and modularity. We have evaluated the ability of enzymatically crosslinked hyaluronic acid (HA) microgel bioinks to form mature cartilage in vivo. Microgel bioinks were formed by mechanically sizing bulk HA-tyramine hydrogels through meshes with aperture diameters of 40, 100 or 500 µm. Annealing of the microgels was achieved by crosslinking residual tyramines. Secondary crosslinked scaffolds were stable in solution and showed tunable porosity from 9% to 21%. Bioinks showed excellent rheological properties and were used to print different objects. Printing precision was found to be directly correlated to microgel size. As a proof of concept, freeform reversible embedding of suspended hydrogels printing with gelation triggered directly in the bath was performed to demonstrate the versatility of the method. The granular hydrogels support the homogeneous development of mature cartilage-like tissues in vitro with mechanical stiffening up to 200 kPa after 63 d. After 6 weeks of in vivo implantation, small-diameter microgels formed stable constructs with low immunogenicity and continuous tissue maturation. Conversely, increasing the microgel size resulted in increased inflammatory response, with limited stability in vivo. This study reports the development of new microgel bioinks for cartilage tissue biofabrication and offers insights into the foreign body reaction towards porous scaffolds implantation.

Hyaluronic acid-based biphasic scaffold with layer-specific induction capacity for osteochondral defect regeneration

The repair of cartilage and subchondral bone defects, especially the former, remains a challenge in clinical practice. An increasing number of studies have shown that the use of biomaterials has great advantages in regulating tissue repair, with lower cost and risk than the use of cytokines or cells. However, great challenges remain because of the marked differences between cartilage and subchondral bone. Here, biphasic osteochondral scaffolds with layer-specific differentiation were designed and developed. Hyaluronic acid (HA) was used as the matrix in the upper and lower layers, and differences in physicochemical properties and biological properties between the two layers were realized by different chemical crosslinking methods. The cartilage regeneration layer exhibited stress relaxation from the HA hydrazone crosslinking dynamics. Additionally, a porous HA hydrogel with dominant elasticity was prepared for subchondral bone repair. Importantly, a 3D-printed scaffold bracket could keep close integration of two layers and provided mechanical support, aiding the long-term tissue regeneration process. The in vitro and in vivo results indicated that the HA-base bilayer scaffold consisting of a dynamic HA layer and a porous HA layer realized the simultaneous integrated regeneration of articular cartilage and subchondral bone. Such scaffolds represent potential new materials for osteochondral regeneration.

Biomaterial-Mediated Presentation of Jagged-1 Mimetic Ligand Enhances Cellular Activation of Notch Signaling and Bone Regeneration.

The development from stem cells to adult tissues requires the delicate presentation of numerous crucial inductive cues and the activation of associated signaling pathways. The Notch signaling pathways triggered by ligands such as Jagged-1 have been demonstrated to be essential in various development processes especially in osteogenesis and ossification. However, few studies have capitalized on the osteoinductivity of the Jagged-1 mimetic ligands to enhance the osteogenesis and skeleton regeneration. In this study, we conjugate the porous hyaluronic acid hydrogels with a Jagged-1 mimetic peptide ligand (Jagged-1) and investigate the efficacy of such biomimetic functionalization to promote the mechanotransduction and osteogenesis of human mesenchymal stem cells by activating the Notch signaling pathway. Our findings indicate that the immobilized Jagged-1 mimetic ligand activates Notch signaling via the upregulation of NICD and downstream MSX2, leading to the enhanced mechanotransduction and osteogenesis of stem cells. We further demonstrate that the functionalization of the Jagged-1 ligand in the porous scaffold promotes angiogenesis, regulates macrophage recruitment and polarization, and enhances in situ regeneration of rat calvarial defects. Our findings provide valuable guidance to the design of development-inspired bioactive biomaterials for diverse biomedical applications.

Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process.

Injectable hydrogels have been widely applied in the field of regenerative medicine. However, current techniques for injectable hydrogels are facing a challenge when trying to generate a biomimetic, porous architecture that is well-acknowledged to facilitate cell behaviors. In this study, an injectable, interconnected, porous hyaluronic acid (HA) hydrogel based on an in-situ bubble self-generation and entrapment process was developed. Through an amide reaction between HA and cystamine dihydrochloride activated by EDC/NHS, CO2 bubbles were generated and were subsequently entrapped inside the substrate due to a rapid gelation-induced retention effect. HA hydrogels with different molecular weights and concentrations were prepared and the effects of the hydrogel precursor solution’s concentration and viscosity on the properties of hydrogels were investigated. The results showed that HA10-10 (10 wt.%, MW 100,000 Da) and HA20-2.5 (2.5 wt.%, MW 200,000 Da) exhibited desirable gelation and obvious porous structure. Moreover, HA10-10 represented a high elastic modulus (32 kPa). According to the further in vitro and in vivo studies, all the hydrogels prepared in this study show favorable biocompatibility for desirable cell behaviors and mild host response. Overall, such an in-situ hydrogel with a self-forming bubble and entrapment strategy is believed to provide a robust and versatile platform to engineer injectable hydrogels for a variety of applications in tissue engineering, regenerative medicine, and personalized therapeutics.

Porous Biomimetic Hyaluronic Acid and Extracellular Matrix Protein Nanofiber Scaffolds for Accelerated Cutaneous Tissue Repair.

Recent reports suggest the utility of extracellular matrix (ECM) molecules as raw components in scaffolding of engineered materials. However, rapid and tunable manufacturing of ECM molecules into fibrous structures remains poorly developed. Here we report on an immersion rotary jet-spinning (iRJS) method to show high-throughput manufacturing (up to ∼1 g/min) of hyaluronic acid (HA) and other ECM fiber scaffolds using different spinning conditions and postprocessing modifications. This system allowed control over a variety of scaffold material properties, which enabled the fabrication of highly porous (70-95%) and water-absorbent (swelling ratio ∼2000-6000%) HA scaffolds with soft-tissue mimetic mechanical properties (∼0.5-1.5 kPa). Tuning these scaffolds' properties enabled the identification of porosity (∼95%) as a key facilitator for rapid and in-depth cellular ingress in vitro. We then demonstrated that porous HA scaffolds accelerated granulation tissue formation, neovascularization, and reepithelialization in vivo, altogether potentiating faster wound closure and tissue repair. Collectively, this scalable and versatile manufacturing approach enabled the fabrication of tunable ECM-mimetic nanofiber scaffolds that may provide an ideal first building block for the design of all-in-one healing materials.

Simvastatin delivery on PEEK for bioactivity and osteogenesis enhancements

A strategy developed for obtaining positive cellular responses remains to be focused in the filed of functional biomimetics. In this study, a hydrogel covered simvastatin-loaded polyetheretherketone (PEEK) bio-composites was constructed with the purpose of bone tissue regeneration therapy. Briefly, a three-dimensional (3D) porous structure was fabricated on PEEK surface; then the substrate was functionalized with the poly(L-lactic acid)/simvastatin porous film and hyaluronic acid hydrogel subsequently. In vitro cell attachment, proliferation, and cytoskeletal observation experiments reveal that our scaffolds show better bio-affinity due to the layer of hyaluronic acid hydrogel compared with control. Furthermore, the alkaline phosphatase activity, calcium mineral deposition evaluation, and gene expression for osteogenic potential all exhibit that the superior osteogenic differentiation of MC3T3-E1 pre-osteoblasts on our scaffolds. Therefore, our PEEK samples loaded with simvastatin and covered with hyaluronic acid hydrogel hold great potential in clinical applications for bone repair.

Injection of Microporous Annealing Particle (MAP) Hydrogels in the Stroke Cavity Reduces Gliosis and Inflammation and Promotes NPC Migration to the Lesion.

With the number of deaths due to stroke decreasing, more individuals are forced to live with crippling disability resulting from the stroke. To date, no therapeutics exist after the first 4.5 h after the stroke onset, aside from rest and physical therapy. Following stroke, a large influx of astrocytes and microglia releasing proinflammatory cytokines leads to dramatic inflammation and glial scar formation, affecting brain tissue's ability to repair itself. Pathological conditions, such as a stroke, trigger neural progenitor cells (NPCs) proliferation and migration toward the damaged site. However, these progenitors are often found far from the cavity or the peri-infarct tissue. Poststroke tissue remodeling results in a compartmentalized cavity that can directly accept a therapeutic material injection. Here, this paper shows that the injection of a porous hyaluronic acid hydrogel into the stroke cavity significantly reduces the inflammatory response following stroke while increasing peri-infarct vascularization compared to nonporous hydrogel controls and stroke only controls. In addition, it is shown that the injection of this material impacts NPCs proliferation and migration at the subventricular zone niche and results, for the first time, in NPC migration into the stroke site.

Investigation of Overrun-Processed Porous Hyaluronic Acid Carriers in Corneal Endothelial Tissue Engineering.

Hyaluronic acid (HA) is a linear polysaccharide naturally found in the eye and therefore is one of the most promising biomaterials for corneal endothelial regenerative medicine. This study reports, for the first time, the development of overrun-processed porous HA hydrogels for corneal endothelial cell (CEC) sheet transplantation and tissue engineering applications. The hydrogel carriers were characterized to examine their structures and functions. Evaluations of carbodiimide cross-linked air-dried and freeze-dried HA samples were conducted simultaneously for comparison. The results indicated that during the fabrication of freeze-dried HA discs, a technique of introducing gas bubbles in the aqueous biopolymer solutions can be used to enlarge pore structure and prevent dense surface skin formation. Among all the groups studied, the overrun-processed porous HA carriers show the greatest biological stability, the highest freezable water content and glucose permeability, and the minimized adverse effects on ionic pump function of rabbit CECs. After transfer and attachment of bioengineered CEC sheets to the overrun-processed HA hydrogel carriers, the therapeutic efficacy of cell/biopolymer constructs was tested using a rabbit model with corneal endothelial dysfunction. Clinical observations including slit-lamp biomicroscopy, specular microscopy, and corneal thickness measurements showed that the construct implants can regenerate corneal endothelium and restore corneal transparency at 4 weeks postoperatively. Our findings suggest that cell sheet transplantation using overrun-processed porous HA hydrogels offers a new way to reconstruct the posterior corneal surface and improve endothelial tissue function.

Influence of Pre-Freezing Temperature on the Corneal Endothelial Cytocompatibility and Cell Delivery Performance of Porous Hyaluronic Acid Hydrogel Carriers.

The development of porous hyaluronic acid (HA) hydrogels for corneal endothelial tissue engineering is attractive because they can be used as functional cell delivery carriers to help in the reconstruction of damaged areas. The purpose of this study was to investigate the corneal endothelial cytocompatibility and cell delivery performance of porous HA hydrogel biomaterials fabricated at different pre-freezing temperatures. As compared to their counterparts prepared at −80 °C, the HA samples fabricated at higher pre-freezing temperature (i.e., 0 °C) exhibited a larger pore size and higher porosity, thereby leading to lower resistance to glucose permeation. Live/dead assays and gene expression analyses showed that the restricted porous structure of HA carriers decreases the viability and ionic pump function of cultured corneal endothelial cells (CECs). The results also indicated that the porous hydrogel biomaterials fabricated at high pre-freezing temperature seem to be more compatible with rabbit CECs. In an animal model of corneal endothelial dysfunction, the wounded rabbit corneas receiving bioengineered CEC sheets and restricted porous-structured HA carriers demonstrated poor tissue reconstruction. The therapeutic efficacy of cell sheet transplants can be improved by using carrier materials prepared at high pre-freezing temperature. Our findings suggest that the cryogenic operation temperature-mediated pore microstructure of HA carriers plays an important role in corneal endothelial cytocompatibility and cell delivery performance.

Porous hyaluronic acid hydrogels for localized nonviral DNA delivery in a diabetic wound healing model.

The treatment of impaired wounds requires the use of biomaterials that can provide mechanical and biological queues to the surrounding environment to promote angiogenesis, granulation tissue formation, and wound closure. Porous hydrogels show promotion of angiogenesis, even in the absence of proangiogenic factors. It is hypothesized that the added delivery of nonviral DNA encoding for proangiogenic growth factors can further enhance this effect. Here, 100 and 60 μm porous and nonporous (n-pore) hyaluronic acid-MMP hydrogels with encapsulated reporter (pGFPluc) or proangiogenic (pVEGF) plasmids are used to investigate scaffold-mediated gene delivery for local gene therapy in a diabetic wound healing mouse model. Porous hydrogels allow for significantly faster wound closure compared with n-pore hydrogels, which do not degrade and essentially provide a mechanical barrier to closure. Interestingly, the delivery of pDNA/PEI polyplexes positively promotes granulation tissue formation even when the DNA does not encode for an angiogenic protein. And although transfected cells are present throughout the granulation tissue surrounding, all hydrogels at 2 weeks, pVEGF delivery does not further enhance the angiogenic response. Despite this, the presence of transfected cells shows promise for the use of polyplex-loaded porous hydrogels for local gene delivery in the treatment of diabetic wounds.

Biocompatibility of hyaluronic acid hydrogels prepared by porous hyaluronic acid microbeads

Hyaluronic acid hydrogels (HAHs) were synthesized by immersing HA microbeads crosslinked with divinyl sulfone in a phosphate buffered saline solution to evaluate the biocompatibility of the gels by means of cytotoxicity, genotoxicity (in vitro chromosome aberration test, reverse mutation assay, and in vivo micronucleus test), skin sensitization, and intradermal reactivity. The HAHs induced no cytotoxicity or genotoxicity. In guinea pigs treated with grafts and prostheses, no animals died and there were no abnormal clinical signs. The sensitization scores were zero in all guinea pigs after 24 h and 48 h challenge, suggesting that the HAHs had no contact allergic sensitization in the guinea pig maximization test. No abnormal signs were found in New Zealand White rabbits during the 72 h observation period after the injection. There was no difference between the HAHs and negative control mean scores because skin reaction such as erythema or oedema was not observed after injection. Experimental results suggest that the HAHs would be suitable for soft tissue augmentation due to the absence of cytotoxicity, genotoxicity, skin sensitization, and intradermal reactivity.

Spray-assisted layer-by-layer assembly on hyaluronic acid scaffolds for skin tissue engineering

Tissue engineering approaches for the development of a single epidermal-dermal scaffold to treat full-thickness skin defects have been limited by difficulties in the fabrication of a bilayer scaffold combining the specific properties of the epidermis and the dermis. Here we present an innovative approach to developing a scaffold that holds promise for skin tissue engineering. We utilize the spray-assisted layer-by-layer assembly technique to deposit a polyelectrolyte multilayer film composed of hyaluronic acid and poly-L-lysine (the epidermal component) on a porous hyaluronic acid scaffold (the dermal component), in a rapid and controlled manner. The multilayer film promotes cell adhesion, contributing to regeneration of the epidermal barrier functions of skin. While human keratinocytes attached and proliferated on the coated porous scaffolds, they did not invade the porous dermal component, thus leaving room for seeding of relevant fibroblast cell types in this scaffold. This scaffold therefore holds promise for co-culture of different cells, which may be useful for treatment of full-thickness skin defects as well as other tissue engineering applications.

Non-viral DNA delivery from porous hyaluronic acid hydrogels in mice

The lack of vascularization within tissue-engineered constructs remains the primary cause of construct failure following implantation. Porous constructs have been successful in allowing for vessel infiltration without requiring extensive matrix degradation. We hypothesized that the rate and maturity of infiltrating vessels could be enhanced by complementing the open pore structure with the added delivery of DNA encoding for angiogenic growth factors. Both 100 and 60 μm porous and non-porous hyaluronic acid hydrogels loaded with pro-angiogenic (pVEGF) or reporter (pGFPluc) plasmid nanoparticles were used to study the effects of pore size and DNA delivery on angiogenesis in a mouse subcutaneous implant model. GFP-expressing transfected cells were found inside all control hydrogels over the course of the study, although transfection levels peaked by week 3 for 100 and 60 μm porous hydrogels. Transfection in non-porous hydrogels continued to increase over time corresponding with continued surface degradation. pVEGF transfection levels were not high enough to enhance angiogenesis by increasing vessel density, maturity, or size, although by 6 weeks for all pore size hydrogels more hydrogel implants were positive for vascularization when pVEGF polyplexes were incorporated compared to control hydrogels. Pore size was found to be the dominant factor in determining the angiogenic response with 60 μm porous hydrogels having more vessels/area present than 100 μm porous hydrogels at the initial onset of angiogenesis at 3 weeks. The results of this study show promise for the use of polyplex loaded porous hydrogels to transfect infiltrating cells in vivo and guide tissue regeneration and repair.

Chemical sintering generates uniform porous hyaluronic acid hydrogels

The implantation of scaffolds for tissue repair has achieved only limited success due primarily to the inability to achieve vascularization within the construct. Many strategies have therefore moved to incorporate pores into the scaffolds to encourage rapid cellular infiltration and subsequent vascular ingrowth. We utilized an efficient chemical sintering technique to create a uniform network of polymethyl methacrylate (PMMA) microspheres for porous hyaluronic acid hydrogel formation. The porous hydrogels generated from chemical sintering possessed pore uniformity and interconnectivity comparable to the commonly used non- and heat sintering techniques. Moreover, a similar cell response to the porous hydrogels generated from each sintering approach was observed in cell viability, spreading and proliferation in vitro, as well as cellular invasion in vivo. We propose chemical sintering of PMMA microspheres using a dilute acetone solution as an alternative method to generate porous hyaluronic acid hydrogels since it requires equal or 10-fold less processing time as the currently used non-sintering or heat sintering technique, respectively.

Proliferation and chondrogenic differentiation of human adipose-derived mesenchymal stem cells in porous hyaluronic acid scaffold

Human adipose-derived mesenchymal stem cells (AD-MSCs) attracted much interest as a promising alternative to autologous chondrocytes and bone marrow-derived mesenchymal stem cells for cartilage regeneration. Developing a suitable culture technique to direct AD-MSCs into the chondrogenic lineage could be a crucial prerequisite for the cartilage defect repair application of AD-MSCs. Herein, we prepared the PEGDG-crosslinked porous three-dimensional (3D) hyaluronic acid (HA) scaffold and evaluated for its feasibility to induce proliferation and chondrogenic differentiation of the AD-MSCs. In addition, the effect of bone-morphogenetic protein-2 (BMP-2) and platelet-derived growth factor (PDGF) on chondrogenic differentiation was further investigated. Proliferation and chondrogenic differentiation were evaluated by cell morphology, DNA contents, s-GAG contents, and level of mRNA expression of relevant marker genes. When cultured with reference chondrogenic medium (RCM; serum-free DMEM-HG supplemented with 10 ng/mL of transforming growth factor-β1 (TGF-β1), 50 nM ascorbate, 100 nM dexamethasone, and 5 μg/mL of ITS), better proliferation and chondrogenic differentiation of AD-MSCs were obtained in the 3D HA scaffold culture as compared to the micromass culture, a standard 3D culture system. Moreover, the level of chondrogenic differentiation of AD-MSCs in the HA scaffold-RCM culture system was further increased by BMP-2, and decreased by PDGF. These results suggested that the HA scaffold with RCM was a promising chondrogenic culture system of AD-MSCs, and that BMP-2 could potentially serve as a chondrogenic supplement for AD-MSCs. However, PDGF was determined to be an inappropriate supplement based on its inhibition of the chondrogenic differentiation of AD-MSCs.

Preparation of Open Porous Hyaluronic Acid Scaffolds for Tissue Engineering Using the Ice Particulate Template Method

A novel method to fabricate highly interconnected porous hyaluronic acid (HA) scaffolds with open surface pore structures was developed by using embossed ice particulates as a template. HA sponges were cross-linked by water-soluble carbodiimide (WSC) and the optimal cross-linking condition was analyzed by infrared spectroscopy. Cross-linking with 50 mM WSC in a 90% (v/v) ethanol/water solvent mixture assured the highest degree of cross-linking and most stable structure and, therefore, was used to cross-link the HA sponges. Observation with a scanning electron microscope showed that the HA scaffolds had funnel-like porous structures. There were large, open pores on the top surfaces and inner bulk pores under the top surface of the funnel-like HA sponges. The inner bulk pores were interconnected with the large, top surface pores and extended into the whole sponge. The pore morphology and density of the large, top surface pores were dependent on the dimension and density of the ice particulates. The size of the inner bulk pores was dependent on the freezing temperature. The funnel-like pore structures of the HA sponges facilitated cell penetration into the inner pores of the sponges and resulted in homogenous cell distribution in the sponges.

Crystal templating dendritic pore networks and fibrillar microstructure into hydrogels

Native tissues contain space-filling dendritic pore networks, such as vasculature, for the efficient distribution of oxygen and nutrients; however, it is not yet possible to create tissue-engineered scaffolds with dendritic porosity. Fibers are also important structural features of native tissues because they provide sites for cell anchorage, promote cell guidance and contribute to mechanical stability. Here, we have developed a “crystal templating” technique, which is simple and inexpensive, for fabricating polymer scaffolds with space-filling dendritic pore networks and fibrillar microtopography. To do this, we grow dendritic urea crystals in solution cast films of hyaluronic acid (HA), photocrosslink the HA around the crystal network to lock in the dendritic configuration, and dissolve the crystals to obtain empty pores. During in situ crystal growth the HA biopolymer is phase separated from the long narrow urea crystals and shaped into a fibrillar microstructure. The porous fibrillar HA scaffolds created by crystal templating may be applicable as regenerative patches for skin and other tissues.

Fabrication of Apatite-Hyaluronic Acid Hybrids

Apatite-polymer hybrids have been attractive as novel bone-bonding bioactive bone substitutes with mechanical performances analogous to those of natural bone. It is shown that carboxyl group (COOH) can induce the apatite nucleation in an environment of simulated body fluid (SBF). In the present study, we fabricated porous hyaluronic acid gels abundant in COOH group and investigated their apatite formation ability in SBF. Hyaluronic acid has been attractive for boneand cartilagerepairing materials due to high biological compatibility. We attempted the preparation of bioactive organic-inorganic hybrids from Hyaluronic acid. It has been attractive for boneand cartilage-repairing materials due to high biological compatibility. It is known that divinyl sulfone is a candidate of cross-linker to bridge the hydroxyl groups. The hydroxyl group of hyaluronic acid side chains were bridged by divinyl sulfone. Porous hyaluronic acid gels stable in aqueous environment were obtained by appropriate crosslinking. They formed the apatite on their surfaces in SBF, when they were priorly treated with CaCl2 aqueous solution. In addition, trehalose, a kind of disaccharide, is found to increase the pore size of the porous hyaluronic acid. This suggests that the pore size and porosity can be controlled by addition of trehalose during fabrication of the scaffolds.

Production of morphology-controllable porous hyaluronic acid particles using a spray-drying method

Hyaluronic acid (HA) porous particles with controllable porosity and pore size, ranging from 100 to 300 nm, were successfully prepared using a colloidal templating and spray-drying method. HA powder and polystyrene latex (PSL) particles, which were used as the precursor and templating agent, respectively, were mixed in aqueous solution and spray-dried using a two-fluid nozzle system to produce HA and PSL composite particles. Water was evaporated during spray-drying using heated air with a temperature of 120 °C. This simple process was completed within several seconds. The prepared particles were collected and washed with an organic solvent to dissolve the PSL templating agent. The porosity and pore size of the resulting particles were easily controlled by changing the initial mass ratio of precursor to templating agent, i.e., HA to PSL, and by altering the size of the PSL template particles.