Photocrosslinked Alginate Research Articles

Copper ions-photo dual-crosslinked alginate hydrogel for angiogenesis and osteogenesis.

Early healing of bone defects is still a clinical challenge. Many bone-filling materials have been studied, among which photocrosslinked alginate has received significant attention due to its good biocompatibility and morphological plasticity. Although it has been confirmed that photocrosslinked alginate can be used as an extracellular matrix for 3D cell culture, it lacks osteogenesis-related biological functions. This study constructed a copper ions-photo dual-crosslinked alginate hydrogel scaffold by controlling the copper ion concentration. The scaffolds were shaped by photocrosslinking and then endowed with biological functions by copper ions crosslinking. According to in vitro research, the dual-crosslinked hydrogel increased the compressive strength and favored copper dose-dependent osteoblast differentiation and cell surface adherence of rat bone marrow mesenchymal stem cells and the expression of type I collagen (Col1), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), vascular endothelial growth factor (VEGF). In addition, hydrogel scaffolds were implanted into rat skull defects, and more angiogenesis and osteogenesis could be observed in in vivo studies. The above results show that the copper-photo-crosslinked hydrogel scaffold has excellent osseointegration properties and can potentially promote angiogenesis and early healing of bone defects, providing a reference solution for bone tissue engineering materials.

Enhanced osteogenic and bactericidal performance of premixed calcium phosphate cement with photocrosslinked alginate thin film.

The increasing prevalence of implant-associated infections (IAI) in orthopedics remains a public health challenge. Calcium phosphates (CaPs) are critical biomaterials in dental treatments and bone regeneration. It is highly desirable to endow CaPs with antibacterial properties. To achieve this purpose, we developed a photocrosslinked methacrylated alginate co-calcium phosphate cement (PMA-co-PCPC) with antibacterial properties, using α-tricalcium phosphate (α-TCP) powders with 16% amorphous contents as solid phase, liquid phases containing CuCl2 and SrCl2 as an inhibitor, and CaCl2 as an activator to construct PCPC. When CaCl2 started to activate the hydration reaction, Sr2+ or Cu2+ ions were exchanged with Ca2+, and α-TCP dissolution was restarted and gradually hydrated to form calcium-deficient hydroxyapatite (CDHA). PMA was added to crosslink with Cu/Sr ions and form gel-layer-wrapped hydrated CDHA. This study explored the binding mechanism of PMA and PCPC and the ion release rule of Ca2+ → Sr2+/Cu2+, optimized the construction of several antibacterial PMA-co-PCPC materials, and analyzed the physical, chemical, and biological properties. Because of the combined effect of Cu and Sr ions, the scaffold exhibited a potential antibacterial activity, promoting bone formation and vascular regeneration. This work provides a basis for designing antibacterial calcium phosphate biomaterials with controllable treatment, which is an important characteristic for preventing IAI of biomaterials.

Visible light-crosslinkable tyramine-conjugated alginate-based microgel bioink for multiple cell-laden 3D artificial organ

While the natural carbohydrate alginate has enabled effective three-dimensional (3D) extrusion bioprinting, it still suffers from some issues such as low printability and resolution and limited cellular function due to ionic crosslinking dependency. Here, we prepared a harmless visible light-based photocrosslinkable alginate by chemically bonding tyrosine-like residues onto alginate chains to propose a new microgel manufacturing system for the development of 3D-printed bioinks. The photocrosslinkable tyramine-conjugated alginate microgel achieved both higher cell viability and printing resolution compared to the bulk gel form. This alginate-based jammed granular microgel bioink showed excellent 3D bioprinting ability with maintained structural stability. As a biocompatible material, the developed multiple cell-loaded photocrosslinkable alginate-based microgel bioink provided excellent proliferation and migration abilities of laden living cells, providing an effective strategy to construct implantable functional artificial organ structures for 3D bioprinting-based tissue engineering.

Degradation-Kinetics-Controllable and Tissue-Regeneration-Matchable Photocross-linked Alginate Hydrogels for Bone Repair.

Photocross-linked alginate hydrogels, due to their biodegradability, biocompatibility, strong control for gelling kinetics in space and time, and admirable adaptability for in situ polymerization with a minimally invasive approach in surgical procedures, have created great expectations in bone regeneration. However, hydrogels with suitable degradation kinetics that can match the tissue regeneration process have not been designed, which limits their further application in bone tissue engineering. Herein, we finely developed an oxidation strategy for alginate to obtain hydrogels with more suitable degradation rates and comprehensively explored their physical and biological performances in vitro and in vivo to further advance the clinical application for the hydrogels in bone repair. The physical properties of the gels can be tuned via tailoring the degree of alginate oxidation. In particular, in vivo degradation studies showed that the degradation rates of the gels were significantly increased by oxidizing alginate. The activity, proliferation, initial adhesion, and osteogenic differentiation of rat and rabbit bone marrow stromal cells (BMSCs) cultured with/in the hydrogels were explored, and the results demonstrated that the gels possessed excellent biocompatibility and that the encapsulated BMSCs were capable of osteogenic differentiation. Furthermore, in vivo implantation of rabbit BMSC-loaded gels into tibial plateau defects of rabbits demonstrated the feasibility of hydrogels with appropriate degradation rates for bone repair. This study indicated that hydrogels with increasingly controllable and matchable degradation kinetics and satisfactory bioproperties demonstrate great clinical potential in bone tissue engineering and regenerative medicine and could also provide references for drug/growth-factor delivery therapeutic strategies for diseases requiring specific drug/growth-factor durations of action.

Effect of low aspect ratio one-dimensional nanoparticles on properties of photocrosslinked alginate nanocomposite hydrogels

One-dimensional nanoparticles such as fibers, wires, represent an exciting type of filler for obtaining nanocomposite hydrogels due to their high aspect ratio. Unlike continuous fibers, in composites with short fibers, stress transfer occurs not only at the cylindrical surface of the fiber but also at the fiber ends. This work aimed to study the influence of the length of low aspect ratio one-dimensional nanoparticles on the rheological, swelling and thermal properties of nanocomposite hydrogels. We synthesized nanocomposite hydrogels via photopolymerization of methacrylated alginate macromonomers and aluminum oxide nanoparticles, nanowires and nanofibers as fillers. The main difference between the nanoparticles lies in their length. Longer nanoparticles (nanofibers) provided a glassier structure and a more significant reinforcement to the hydrogel, for example, at the concentration of 0.5 wt% the complex modulus increased approximately 2-fold and 8-fold for nanowires and nanofibers, respectively. Similarly, the incorporation of nanofibers produced hydrogels with a lower swelling capacity (2.5-fold decrease), which was attributed to a more connected network structure due to the higher aspect ratio of the nanofibers. Finally, both nanoparticle types produced an increase in the activation energy of thermal degradation.

Bio-functional strontium-containing photocrosslinked alginate hydrogels for promoting the osteogenic behaviors

In recent years, photocrosslinked alginate hydrogel has been widely studied in bone tissue engineering, owing to its numerous advantages. However, there are still some shortcomings like insufficient mechanical strength and lack of bone induction. To compensate for these deficiencies, in this work, a novel doped strontium (Sr) photocrosslinked methacrylated alginate (Sr-PMA) hydrogel was developed. Photocrosslinked alginate hydrogel fabricated via crosslinking methacrylate-modified alginate under ultraviolet (UV) light was placed into strontium solutions to prepare Sr-PMA gel by chelating reaction. The chemical structures, swelling behaviors, degradation profiles, elastic moduli, Sr2+ ion release and surface morphology of the Sr-PMA hydrogel were characterized, and we found that physical properties of the gels can be tailored by varying concentration of Sr2+ ions. And MC3T3-E1 cell viability, proliferation and mineralization outside the hydrogel were also investigated. Further research on cell survival, multiplication, osteogenic differentiation of the cells encapsulated in Sr-PMA hydrogels were explored. In vitro studies of biological properties revealed that incorporation of Sr2+ into photocrosslinked alginate gels significantly improved osteogenic differentiation capabilities and mineralization via stimulating expression of osteogenesis related genes and proteins of the cells compared to strontium-free photocrosslinked alginate gels. The research demonstrates that the innovative Sr-PMA hydrogels possessing adjustable physical performances, excellent biocompatibility and osteogenic differentiation capabilities could be potentially applied to bone tissue engineering and regenerative medicine. Meanwhile, it also provides a reference for the modification of biological properties of biomaterials.

3D Encapsulation and tethering of functionally engineered extracellular vesicles to hydrogels

Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) in their naïve and engineered forms have emerged as potential alternatives to stem cell therapy. While they have a defined therapeutic potential, the spatial and temporal control of their activity in vivo remains a challenge. The objective of this study was to devise a methodology to encapsulate EVs in 3D hydrogels for prolonged delivery. To achieve this, we have leveraged the MSC EV interactions with ECM proteins and their derivative peptides. Using osteoinductive functionally engineered EVs (FEEs) derived from MSCs, we show that FEEs bind to mimetic peptides from collagen (DGEA, GFPGER) and fibronectin (RGD). In in vitro experiments, photocrosslinkable alginate hydrogels containing RGD were able to encapsulate, tether and retain the FEEs over a period of 7 days while maintaining the structural integrity and osteoinductive functionality of the EVs. When employed in a calvarial defect model in vivo, alginate-RGD hydrogels containing the FEEs enhanced bone regeneration by a factor of 4 compared to controls lacking FEEs and by a factor of 2 compared to controls lacking the tethering peptide. These results show that EVs can be tethered to biomaterials to promote bone repair and the importance of prolonged delivery in vivo. Results also provide a prelude to the possible use of this technology for controlled delivery of EVs for other regenerative medicine applications. Statement of significanceThe beneficial effects of human MSC (HMSC) therapy are attributable to paracrine effects of the HMSC derived EVs. While EV engineering has the potential to impact several fields of regenerative medicine, targeted delivery of the engineered EVs with spatial and temporal control is necessary to prevent off-target effects and enhance tissue specificity. Here, we have leveraged the interactions of MSC EVs with ECM proteins to develop a tethering system that can be utilized to prolong EV delivery in vivo while maintaining the structural and functional integrity of the EVs. Our work has provided a tunable platform for EV delivery that we envision can be formulated as an injectable material or a bulk hydrogel suitable for regenerative medicine applications.

Photo-crosslinked alginate nano-hydroxyapatite paste for bone tissue engineering

In this study, methacrylation of alginate was carried out by reacting sodium alginate with methacrylic anhydride in the presence of sodium hydroxide. Separately synthesized nano-hydroxyapatite (nano-HAp) powder was surface functionalized using mercaptopropionic acid and ethylene glycol methacrylate phosphate (EGMP) in the presence of azobisisobutyronitrile benzene as a free radical initiator in a nitrogen atmosphere. Methacrylated alginate solution was mixed with the required amount of surface-functionalized HAp nanoparticles in the presence of 0.05% Irgacure 2959 as a photoinitiator and was placed at the centre of a 8 kW UV light source (265 nm) to prepare photo-crosslinked bone paste. X-ray diffraction analysis indicated that surface functionalization did not alter phase purity of HAp nanopowder in the prepared paste. The graft polymerization of EGMP on the surface of HAp was confirmed by the presence of the 1732 cm−1 band, which belongs to C=-O stretching of EGMP, in addition to the characteristic peaks of nano-HAp and alginate in the composite paste. The storage and loss moduli of all the prepared pastes increased non-linearly with time up to 100 s, demonstrating their pseudo plastic behaviour. The rate of release of bone morphogenetic protein 2 (BMP-2) was significantly faster in the first few days, and the release curve gradually levelled off prior to slowing down up to 22 d. Mesenchymal stem cell adhesion studies revealed that cells could attach to the paste material and stretch over the surface of the material after 14 d of incubation. MTT assay showed that prepared paste materials were conducive to attachment and proliferation of mesenchymal stem cells. Immunocytochemical analysis revealed that the addition of surface-functionalized nano-HAp and BMP-2 to alginate hydrogel enhanced the osteogenic potential of the prepared paste. The results indicate that the newly developed photo-crosslinked paste may be physically and biologically suitable for application as a bone filler.

Effect of altering photocrosslinking conditions on the physical properties of alginate gels and the survival of photoencapsulated cells

Research on biocompatible photocrosslinked organic chemical polymers for applications in biomedicine and tissue engineering has achieved satisfactory results, such as repairing or augmenting tissues. Photocrosslinked alginate gel is one of those polymers. However, there is little information in the literature regarding the preparation of photocrosslinked alginate hydrogels with high cell activity and appropriate mechanical properties by using suitable photoinitiator concentrations and reasonable ultraviolet (UV) exposure times. In this work, photocrosslinked alginate hydrogels formed with different concentrations of photoinitiator or UV exposure times were characterized by testing their mechanical properties and the viability of photoencapsulated osteoblast-like cells. To explore the degree of photocrosslinking of methacrylated alginate, the 1H NMR spectra of the gels were recorded with an NMR spectrometer, and the results showed that methacrylated alginate did not photocrosslink completely at low photoinitiator concentrations or for short UV exposure times. It was also revealed that the swelling behaviour, degradation profiles and elastic moduli of the hydrogel are tuneable by varying the photoinitiator concentration or UV exposure time. In addition, the viability and proliferation of the cells photoencapsulated in the gels gradually decreased with increasing photoinitiator concentration or UV exposure time. However, when the photoinitiator concentration and UV exposure time were controlled within a reasonable range, the cells in the gels maintained their high activity. In summary, the results indicated that the performance of the hydrogels could be tailored by adjusting the concentrations of photoinitiator or UV exposure time. This research may be used to further optimize cell photoencapsulation and photopolymerization strategies of photocrosslinked alginate gels or other biophotopolymers in tissue engineering and biomedicine and provides a theoretical basis for related research and future applications.

Chondroinductive Alginate-Based Hydrogels Having Graphene Oxide for 3D Printed Scaffold Fabrication.

Scaffolds based on bioconjugated hydrogels are attractive for tissue engineering because they can partly mimic human tissue characteristics. For example, they can further increase their bioactivity with cells. However, most of the hydrogels present problems related to their processability, consequently limiting their use in 3D printing to produce tailor-made scaffolds. The goal of this work is to develop bioconjugated hydrogel nanocomposite inks for 3D printed scaffold fabrication through a micro-extrusion process having improved both biocompatibility and processability. The hydrogel is based on a photocrosslinkable alginate bioconjugated with both gelatin and chondroitin sulfate in order to mimic the cartilage extracellular matrix, while the nanofiller is based on graphene oxide to enhance the printability and cell proliferation. Our results show that the incorporation of graphene oxide into the hydrogel inks considerably improved the shape fidelity and resolution of 3D printed scaffolds because of a faster viscosity recovery post extrusion of the ink. Moreover, the nanocomposite inks produce anisotropic threads after the 3D printing process because of the templating of the graphene oxide liquid crystal. The in vitro proliferation assay of human adipose tissue-derived mesenchymal stem cells (hADMSCs) shows that bioconjugated scaffolds present higher cell proliferation than pure alginate, with the nanocomposites presenting the highest values at long times. Live/Dead assay otherwise displays full viability of hADMSCs adhered on the different scaffolds at day 7. Notably, the scaffolds produced with nanocomposite hydrogel inks were able to guide the cell proliferation following the direction of the 3D printed threads. In addition, the bioconjugated alginate hydrogel matrix induced chondrogenic differentiation without exogenous pro-chondrogenesis factors as concluded from immunostaining after 28 days of culture. This high cytocompatibility and chondroinductive effect toward hADMSCs, together with the improved printability and anisotropic structures, makes these nanocomposite hydrogel inks a promising candidate for cartilage tissue engineering based on 3D printing.

OSCILLATORY STRAIN SWEEPS OF HYDROGELS FROM METHACRYLATED ALGINATE MACROMONOMERS: ASSESSMENT OF SYNTHESIS AND ACQUISITION VARIABLES

The objective of this study is the rheological characterization of photocrosslinked alginate hydrogels synthesized from methacrylated alginate macromonomers. We first optimized the rheological acquisition parameters for this hydrogels, that is, we studied the influence of the geometries diameter, distance between plates (gap), and solvent trap in the rheological response. Our results show important variations of shear storage modulus, G’, and yield strain with the three parameters measured. Secondly, with the optimized experimental parameters, rheological tests were performed on hydrogels synthesized under different conditions. Three parameters were studied; UV exposure time (polymerization time), macromonomer concentration and photoinitiator concentration. Our data indicate that the polymerization time and the macromonomer concentration have an important effect on the viscoelastic properties of the hydrogel, significantly modifying the shear storage modulus, G’, and the yield strain while the photoinitiator concentration did not influence the viscoelastic properties.

Preparation of drug-immobilized anti-adhesion agent using visible light-curable alginate derivative containing furfuryl group

This study demonstrated the anti-adhesion and wound healing effect of a visible light curable anti-adhesion agent using an alginate derivative modified with a furfuryl moiety. Visible light-curable furfuryl alginate (F-Alg) was prepared in conjugation with alginate and furfurylamine by an amide coupling reaction, and the conjugated F-Alg was characterized by 1H NMR analysis. The cytotoxicity, cell adhesion, and cell permeability of the F-Alg were evaluated for use in anti-adhesion applications. Drug immobilization and protein release were assessed to verify whether the alginate derivatives and drugs were photo-immobilized. In in vivo anti-adhesion testing, the new anti-adhesion agent prepared in this study acted as a physical protective layer by forming a biofilm on the surgical site. Additionally, along with gradual decomposition of the photo-crosslinked alginate derivative, the immobilized drug was released, and additional effects such as accelerated wound healing are expected. Thus, visible light-curable F-Alg has good application potential as an anti-adhesion agent.

Bone Morphogenetic Protein-2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels.

There is a substantial need to prolong cell persistence and enhance functionality in situ to enhance cell-based tissue repair. Bone morphogenetic protein-2 (BMP-2) is often used at high concentrations for osteogenic differentiation of mesenchymal stem cells (MSCs) but can induce apoptosis. Biomaterials facilitate the delivery of lower doses of BMP-2, reducing side effects and localizing materials at target sites. Photocrosslinked alginate hydrogels (PAHs) can deliver osteogenic materials to irregular-sized bone defects, providing improved control over material degradation compared to ionically cross-linked hydrogels. It is hypothesized that the delivery of MSCs and BMP-2 from a PAH increases cell persistence by reducing apoptosis, while promoting osteogenic differentiation and enhancing bone formation compared to MSCs in PAHs without BMP-2. BMP-2 significantly decreases apoptosis and enhances survival of photoencapsulated MSCs, while simultaneously promoting osteogenic differentiation in vitro. Bioluminescence imaging reveals increased MSC survival when implanted in BMP-2 PAHs. Bone defects treated with MSCs in BMP-2 PAHs demonstrate 100% union as early as 8 weeks and significantly higher bone volumes at 12 weeks, while defects with MSC-entrapped PAHs alone do not fully bridge. This study demonstrates that transplantation of MSCs with BMP-2 in PAHs achieves robust bone healing, providing a promising platform for bone repair.

Dual Ionic and Photo-Crosslinked Alginate Hydrogels for Micropatterned Spatial Control of Material Properties and Cell Behavior.

Biomaterial properties such as mechanics, degradation rate, and cell adhesivity affect cell behaviors including spreading, proliferation, and differentiation. To engineer complex tissues, it is often desirable to achieve precise spatial control over these properties. Here, methacrylated alginate (MA-ALG) was used to create hydrogels comprising a single base material with regions of different types and levels of crosslinking and subsequently different material properties. Ionic and ultraviolet light crosslinking mechanisms were combined to create dual-crosslinked hydrogels with significantly increased stiffness and decreased swelling compared to calcium-crosslinked or UV-crosslinked hydrogels. MC3T3 cells showed significantly enhanced proliferation on the surface of dual-crosslinked hydrogels compared with calcium-crosslinked hydrogels. Photomasks were then used to create patterned hydrogels with precise spatial control over regions that were only calcium-crosslinked versus dual-crosslinked. This spatial variation in crosslinking mechanism permitted local regulation of the hydrogel physical properties and alignment of cells seeded on their surface. Photomasks were also used to create hydrogels with patterned presentation of cell adhesion ligands, leading to spatial control over cell attachment and proliferation. This biomaterial system can be useful for providing patterned, instructive cues to guide cell behavior for engineering complex tissues.

Incorporation of magnesium ions into photo-crosslinked alginate hydrogel enhanced cell adhesion ability.

Photo-crosslinked alginate hydrogel attracts wide interest in tissue engineering because of its excellent controllability and stability. However, its highly hydrophilic property makes cell adhesion difficult. Plenty of studies have confirmed that magnesium ions (Mg(2+) ) can efficiently improve the attachment of osteoblasts. In this study, for the first time, we fabricated a durable, crosslinked, alginate hydrogel with a dual-crosslinking network. Photo-crosslinked alginate hydrogel was chosen as the basic backbone, and various amounts of Mg(2+) were incorporated into the hydrogel through ionic crosslinking. The results showed that the physicochemical properties of the hydrogels, including surface structure, composition, swelling ratio, ion release and elastic modulus, could be well tuned by controlling the amount of Mg(2+) incorporated. In addition, a certain amount of Mg(2+) significantly improved the attachment and spread of osteoblasts on the hydrogels. These characteristics make Mg(2+) -incorporated photo-crosslinked alginate hydrogel a promising scaffold for bone tissue engineering.

A New Route Toward IPN Photocrosslinked Alginate Hydrogels with Biodegradation Rates, Excellent Biocompatibility and Mechanical Properties

A New Route Toward IPN Photocrosslinked Alginate Hydrogels with Biodegradation Rates, Excellent Biocompatibility and Mechanical Properties

Photofunctionalization of Alginate Hydrogels to Promote Adhesion and Proliferation of Human Mesenchymal Stem Cells

Photocrosslinkable biomaterials are promising for biomedical applications, as they can be injected in a minimally invasive manner, crosslinked in situ to form hydrogels with cells and/or bioactive factors, and engineered to provide instructive signals to transplanted and host cells. Our group has previously reported on biodegradable, photocrosslinkable alginate (ALG) hydrogels with controlled cell adhesivity for tissue engineering. The polymer backbone of this methacrylated ALG was covalently modified with cell adhesion ligands containing the RGD sequence to enhance the proliferation and differentiation response of encapsulated cells. However, this approach permits limited control over the spatial presentation of these ligands within the three-dimensional hydrogel structure. Here we present a system that easily allows for spatial control of cell adhesion ligands within photocrosslinked ALG hydrogels. A cell adhesive peptide composed of the specific amino acid sequence Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) was covalently modified with acrylate moieties. The acrylated peptide was then covalently incorporated into bulk hydrogels by adding it to methacrylated ALG solutions with a photoinitiator, and then photocrosslinking under long-wave ultraviolet light. The hydrogels were characterized with respect to their swelling and degradation profiles, and the effects of the acrylated peptide on human mesenchymal stem cell (hMSC) viability, adhesion, spreading, and proliferation were examined in vitro. hMSC adhesion and spreading on and proliferation in this biomaterial system could be regulated by varying the concentration of cell adhesion ligand. This new biomaterial system may be a useful platform for tissue engineering, drug delivery, and stem cell transplantation with spatial control of cell adhesivity.

Photocrosslinked alginate with hyaluronic acid hydrogels as vehicles for mesenchymal stem cell encapsulation and chondrogenesis

Ionic crosslinking of alginate via divalent cations allows for high viability of an encapsulated cell population, and is an effective biomaterial for supporting a spherical chondrocyte morphology. However, such crosslinking chemistry does not allow for injectable and stable hydrogels which are more appropriate for clinical applications. In this study, the addition of methacrylate groups to the alginate polymer chains was utilized so as to allow the free radical polymerization initiated by a photoinitiator during UV light exposure. This approach establishes covalent crosslinks between methacrylate groups instead of the ionic crosslinks formed by the calcium in unmodified alginate. Although this approach has been well described in the literature, there are currently no reports of stem cell differentiation and subsequent chondrocyte gene expression profiles in photocrosslinked alginate. In this study, we demonstrate the utility of photocrosslinked alginate hydrogels containing interpenetrating hyaluronic acid chains to support stem cell chondrogenesis. We report high cell viability and no statistical difference in metabolic activity between mesenchymal stem cells cultured in calcium crosslinked alginate and photocrosslinked alginate for up to 10 days of culture. Furthermore, chondrogenic gene markers are expressed throughout the study, and indicate robust differentiation up to the day 14 time point. At early time points, days 1 and 7, the addition of hyaluronic acid to the photocrosslinked scaffolds upregulates gene markers for both the chondrocyte and the superficial zone chondrocyte phenotype. Taken together, we show that photocrosslinked, injectable alginate shows significant potential as a delivery mechanism for cell-based cartilage repair therapies.

Biodegradable photo-crosslinked alginate nanofibre scaffolds with tuneable physical properties, cell adhesivity and growth factor release

Nanofibrous scaffolds are of interest in tissue engineering due to their high surface area to volume ratio, interconnected pores, and architectural similarity to the native extracellular matrix. Our laboratory recently developed a biodegradable, photo-crosslinkable alginate biopolymer. Here, we show the capacity of the material to be electrospun into a nanofibrous matrix, and the ability to enhance cell adhesion and proliferation on these matrices by covalent modification with cell adhesion peptides. Additionally, the potential of covalently incorporating heparin into the hydrogels during the photopolymerisation process to sustain the release of a heparin binding growth factor via affinity interactions was demonstrated. Electrospun photo-crosslinkable alginate nanofibrous scaffolds endowed with cell adhesion ligands and controlled delivery of growth factors may allow for improved regulation of cell behaviour for regenerative medicine.

The effect of oxidation on the degradation of photocrosslinkable alginate hydrogels

Recently, we reported on a new photocrosslinkable alginate-based hydrogel, which has controllable physical and cell adhesive properties. The macromer solution containing cells can be injected in a minimally invasive manner into a defect site and crosslinked while maintaining high cell viability. The number of hydrolyzable ester bonds in the formed crosslinks may be controlled by altering the degree of methacrylation on the alginate polymer backbone. However, the degradation rate of the hydrogels has been found to be slower in vivo than in vitro. The purpose of this study was to develop photocrosslinked alginate hydrogels with an increased range of biodegradation rates for more rapid in vivo biodegradation in regenerative medicine and bioactive factor delivery applications. Therefore, we oxidized alginate prior to methacrylation to change the uronate residue conformations to an open-chain adduct, which makes it more vulnerable to hydrolysis. Here, we demonstrate that the swelling behavior, degradation profiles, and storage moduli of photocrosslinked hydrogels formed from oxidized, methacrylated alginates (OMAs) are tunable by varying the degree of alginate oxidation. The OMA macromers and photocrosslinked OMA hydrogels exhibited cytocompatibility when cultured with human bone marrow-derived mesenchymal stem cells (hBMMSCs). In addition, hMSCs derived from bone marrow or adipose tissue photoencapsulated within these hydrogels remained viable, and their proliferation rate was a function of alginate oxidation level and initial hydrogel weight fraction. Oxidation permits a wider range of photocrosslinked OMA hydrogels physical properties, which may enhance these therapeutic materials’ utility in tissue engineering and other biomedical applications.