Multi-channel biphasic calcium phosphate granules as cell carrier capable of supporting osteogenic priming of mesenchymal stem cells

Abueva, Celine D.G.,Park, Chan Mi,Kim, Boram,Lee, Byong-Taek Elsevier 2018 Materials & Design Vol.141 No.-

<P><B>Abstract</B></P> <P>Advances in bone tissue engineering include versatile and intricate biomaterial scaffolds in combination with stem cells for enhanced bone regeneration. In this study, a unique scaffold with multi-channels designed to allow cell infiltration within its pores was investigated for its capability to serve as a stable platform for adhesion and osteogenic priming of mesenchymal stem cells. The biphasic calcium phosphate multi-channel granule consisted of 60% hydroxyapatite and 40% β-tricalcium phosphate. Successful loading and retention of isolated and expanded rat bone marrow-derived mesenchymal stem cells (rBMSCs) were observed. The cells proliferated within the micro-channels starting from the surface then into the channels. The multi-channel granules were also able to support osteogenic priming of rBMSCs in 2D culture without the aid of a growth factor. Alkaline phosphatase, type I collagen, and runt-related transcription factor 2 expressions were detected with high osteopontin marker expression in as early as 7days, which persisted for 14days of culture under osteogenic condition. Results confirmed commitment towards osteogenic lineage of rBMSCs that have attached and grown onto the surface of the multi-channel granules and thus have high potential as a cell-scaffold based approach in bone regenerative medicine.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Multi-channel BCP granule fabricated by multi-extrusion process successfully served as cell platform for MSCs. </LI> <LI> MSCs attached well on the granule’s surface, while the micro-channel design allowed cell infiltration within the granules. </LI> <LI> Expression of osteogenic markers (ALP, OPN, COL-1 & RUNX 2) confirm successful priming of MSCs and lineage commitment. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Phosphonate-chitosan functionalization of a multi-channel hydroxyapatite scaffold for interfacial implant-bone tissue integration

Abueva, Celine D. G.,Jang, Dong-Woo,Padalhin, Andrew,Lee, Byong-Taek Royal Society of Chemistry 2017 Journal of Materials Chemistry B Vol. No.

<P>Nonunion associated with long bone defects continues to be highly researched both experimentally and clinically. A porous hydroxyapatite (HAp) scaffold has been recognized as a bone repair and substitute material clinically, but its use in segmental bone defects has been limited by poor integration and stability, as a consequence of scaffold strength unmatched with the native bone. Herein, we designed a multi-channel HAp-based scaffold for application in segmental bone defects, with a specific geometry and design. It possesses the required porosity for bone tissue regeneration with sufficient mechanical properties. We also developed a surface functionalization/modification method with the goal of early scaffold integration and stability. Initial functionalization with poly(vinyl phosphonic acid), PVPA, allowed simple attachment of a chitosan polymeric layer. The modification improved the biocompatibility of the scaffold and attachment of rat bone marrow-derived mesenchymal stem cells (rBMSC) <I>in vitro</I>. The modification also served as a buffer between the implant scaffold and bone tissue. Significant improvement in the integration behavior with better interlocking of the scaffold to bone tissue was observed for the modified scaffolds implanted in rabbit tibiae. The modified HAp scaffolds exhibited early interfacial implant-bone tissue integration with enhanced new bone formation and high potential for use in segmental bone defects.</P>

Photoresponsive Hydrogels as Drug Delivery Systems

ABUEVA CELINE,Phil-Sang Chung,류현석,So-Young Park,우승훈 대한의학레이저학회 2020 MEDICAL LASERS Vol.9 No.1

Hydrogels have been developed and used in tissue engineering and regenerative medicine to deliver therapeutics to injured or diseased tissue because of their versatility and properties that can be tailored to match the natural extracellular matrix. Hydrogels can be made with a variety of physical and chemical properties combined with light responsiveness ideal for applications in different fields of medicine that require the spatiotemporal control of therapeutics. Light, as a stimulus, is relatively inexpensive, contact-free, noninvasive with high spatial resolution and temporal control, convenient and easy to use, and allows deep tissue penetration that is relatively harmless. Photoresponsive hydrogels are ideal candidates for on-demand drug delivery systems that are capable of sustained and controlled drug release, minimizing the side effects, and ensuring the activity and efficient delivery of drugs to the target tissue.

Photo-triggered Theranostic Nanoparticles in Cancer Therapy

Celine DG. Abueva 대한의학레이저학회 2021 MEDICAL LASERS Vol.10 No.1

In cancer therapy, it is often desirable to use precision medicine that involves treatments of high specificity. One such treatment is the use of photo-triggered theranostic nanoparticles. These nanoparticles make it possible to visualize and treat tumors specifically in a controlled manner with a single injection. Several novel and powerful photo-triggered theranostic nanoparticles have been developed. These range from small organic dyes, semiconducting and biopolymers, to inorganic nanomaterials such as iron-oxide or gold nanoparticles, carbon nanotubes, and upconversion nanoparticles. Using photo-triggered theranostic nanoparticles and localized irradiation, complete tumor ablation can be achieved without causing significant toxicity to normal tissue. Given the great advances and promising future of theranostic nanoparticles, this review highlights the progress that has been made in the past couple of years, the current challenges faced and offers a future perspective.

Photobiomodulation Therapy in the Treatment of Salivary Dysfunction

Celine DG. Abueva 대한의학레이저학회 2022 MEDICAL LASERS Vol.11 No.1

Photobiomodulation therapy, owing to its photobiological anti-inflam-matory and wound healing effects, has been suggested as a non-invasive, safe, and effective approach in treating salivary dysfunctions. Xerostomia or dry mouth and hyposalivation are challenging conditions, and patients suffer oral problems and a poor quality of life. Several studies have demonstrated the potential of photobiomodulation in reducing xerosto-mia and hyposalivation. However, there is a lack of synthesis of available evidence to establish whether it is an efficient, safe, and cost-effective method. In addition, the challenges include the lack of consensus on the optimal PBM dosage, as well as the variability of the findings in published studies.

BMP-2 Immoblized in BCP-Chitosan-Hyaluronic Acid Hybrid Scaffold for Bone Tissue Engineering

Nath, Subrata Deb,Abueva, Celine,Sarkar, Swapan Kumar,Lee, Byong Taek Materials Research Society of Korea 2014 한국재료학회지 Vol.24 No.12

In this study, we fabricated a novel micro porous hybrid scaffold of biphasic calcium phosphate (BCP) and a polylectrolyte complex (PEC) of chitosan (CS) and hyaluronic acid (HA). The fabrication process included loading of CS-HA PEC in a bare BCP scaffold followed by lypophilization. SEM observation and porosimetry revealed that the scaffold was full of micro and macro pores with total porosity of more than 60 % and pore size in the range of $20{\sim}200{\mu}m$. The composite scaffold was mechanically stronger than the bare BCP scaffold and was significantly stronger than the CS-HA PEC polymer scaffold. Bone morphogenetic growth factor (BMP-2) was immobilized in CS-HA PEC in order to integrate the osteoinductive potentiality required for osteogenesis. The BCP frame, prepared by sponge replica, worked as a physical barrier that prolonged the BMP-2 release significantly. The preliminary biocompatibility data show improved biological performance of the BMP-2 immobilized hybrid scaffold in the presence of rabbit bone marrow stem cells (rBMSC).

Photobiomodulation improves the therapeutic efficacy of mesenchymal stem cells in regenerative medicine

Ken Woo,Celine Abueva 대한의학레이저학회 2022 MEDICAL LASERS Vol.11 No.3

Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into many other cell types typically isolated from adult tissue sources. The therapeutic potential of MSCs is considerable in regenerative medicine and has advanced over the years. Consequently, methods and tools that improve the therapeutic efficacy of MSCs have also been devised and utilized. Recent strategies used to enhance the therapeutic efficacy of MSC include photobiomodulation (PBM), which can increase proliferation and enhance differentiation into target cell types. PBM is a non-thermal, non-invasive method that utilizes light from coherent or non-coherent sources to influence metabolic activity at the cellular level and has been found to increase cell proliferation and migration in vitro, in vivo, and in clinical studies. However, little is known of the mechanism responsible for the effects of PBM on MSCs or its potential as an adjunctive treatment, which obscures appreciation of its regenerative applications. This review summarizes reports on the effects of PBM on different MSCs and provides perspectives on the ability of PBM to improve the therapeutic efficacy of MSCs in regenerative medicine.

Decade Long Survey of Low-level Laser Therapy/ Photobiomodulation (LLLT/PBM) Therapy for Oral Mucositis Treatment

Hyun Seok Ryu,Celine Abueva,Phil-Sang Chung,우승훈 대한의학레이저학회 2021 MEDICAL LASERS Vol.10 No.3

Low-level laser therapy or photobiomodulation (LLLT/PBM) therapy has been widely applied to enhance and accelerate the recovery of oral mucositis. This study investigates the documented effect of LLLT on oral mucositis caused by chemotherapy. This review appraises 6 animal studies and 12 clinical studies published in the Pubmed database during the past 10 years, related to the application of LLLT for the treatment of mucositis. Despite varied parameters and diverse conditions, the assessed articles indicate that application of LLLT on oral mucositis using near-infrared wavelengths is prophylactic, reduces pain, and enables a rapid recovery. Various combined treatments were also identified among the published papers, which further establishes the efficacy of LLLT as a viable treatment.

<i>In vitro</i> and <i>in vivo</i> acute response towards injectable thermosensitive chitosan/TEMPO-oxidized cellulose nanofiber hydrogel

Nguyen, Trang Ho Minh,Abueva, Celine,Ho, Hai Van,Lee, Sun-Young,Lee, Byong-Taek Elsevier 2018 Carbohydrate polymers Vol.180 No.-

<P><B>Abstract</B></P> <P>TEMPO–oxidized cellulose nanofiber (TOCNF) is a natural material with many promising properties, including biocompatibility and degradability. In this study, we integrated TOCNF at different concentrations (0.2, 0.4, 0.6, 0.8% w/v) with chitosan (CS) and created a thermosensitive injectable hydrogel intended for biomedical applications. These hydrogels can undergo sol-gel transition at body temperature through interactions between chitosan and β-glycerophosphate. The addition of TOCNF resulted in faster gelation time and increased porosity. These hydrogels with TOCNF showed improved biocompatibility both <I>in vitro</I> and <I>in vivo</I> compared to CS hydrogel. Both MC3T3-E1 pre-osteoblast cells and L929 fibroblast cells showed biocompatibility towards CS/TOCNF 0.4. After 7days of implantation, initial inflammatory response to CS/TOCNF 0.4 was found. Such response was significantly subsided within 14days. Cell infiltration within the hydrogel was also prominent, showing anti-inflammatory or wound healing (M2) macrophage at 14days after implantation. These results showed that the addition of TOCNF could significantly improve the biocompatibility of CS hydrogel as a biomaterial for biomedical application.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Chitosan (CS)/TEMPO-oxidized cellulose nanofiber (TOCNF) thermosensitive injectable hydrogel. </LI> <LI> CS/TOCNF hydrogel showed good cytocompatibility with both MC3T3-E1 pre-osteoblast and L929 fibroblast cell line. </LI> <LI> Incorporation of TOCNF improved <I>in vivo</I> acute response with more prominent M2 type of macrophage cells. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Enzymatic <i>in situ</i> formed hydrogel from gelatin-tyramine and chitosan-4-hydroxylphenyl acetamide for the co-delivery of human adipose-derived stem cells and platelet-derived growth factor towards vascularization

Linh, Nguyen Thuy Ba,Abueva, Celine D G,Lee, Byong-Taek IOP Publishing 2017 Biomedical materials Vol.12 No.1

<P>An injectable, in situ forming hydrogel system capable of co-delivering human adipose-derived stem cells (hADSC) and platelet-derived growth factor (PDGF) was investigated as a new system for tissue engineering, envisaged to support vascularization. The system consists of tyramine-conjugated gelatin and hydroxyphenyl acetamide chitosan derivative. Both are soluble and stable at physiologic conditions, which is a key factor for retaining viable cells and active growth factor. In situ gelation involved enzymatic crosslinking using horseradish peroxidase as a catalyst and hydrogen peroxide as an oxidant. Gel formation occurred within 30-90 s by controlling the concentration of polymers. PDGF release showed adequate release kinetics within the intended period of time and hADSC showed good compatibility with the hydrogel formulation based on the in vitro assay and subcutaneous implantation into BALB/c-nu/nu nude female mice. Immunohistochemical analysis confirmed viability of delivered hADSC. Histological analysis showed no immune reaction and confirmed blood vessel formation. The results implicate the hydrogel as a promising delivery vehicle or carrier of both cell and growth factor, which support vascularization for tissue engineering applications.</P>