Innovation for the Mankind

50th Anniversary Prince of Songkla UniversityChamuangone Extract with Rice Bran Oil Garcinia cowa is an edible tococcus pyogenes (MIC 7.8 µg/ should be optimized in order toplant commonly known in the mL), S. viridans and Helicobacter get consistently high quality ex-Thai language as “Chamuang”. pylori (MICs 15.6 µg/mL), and tracts that can be effectively usedWe have recently isolated a new Staphylococcus aureus, Bacillus in nutraceutical applications. Apolyprenylated benzophenone subtilis, and Enterococcus spp. method for quantitative analysiscalled “chamuangone” from G. (MICs 31.2 µg/mL). Therefore, of chamuangone in G. cowa leafcowa leaves. Chamuangone pos- G. cowa leaf extracts containing extracts was established using asesses a significant cytotoxic activ- chamuangone may be used po- reversed-phase HPLC. In addition,ity against lung adenocarcinoma tentially as a dietary supplement hexane was a suitable solvent for(SBC3 and A549) and leukemia for prevention of cancer. Thus, extraction of chamuangone from(K562, and K562/ADM) cells with a suitable extraction method asIC50 values of 6.5, 7.5, 3.8, and well as a standardization process2.2 µM, respectively, as well as for preparation of G. cowa leafantibacterial activity against Strep- extracts containing chamuangone92

Innovation for the MankindG. cowa leaves using micro- Awardwave assisted extraction.However, the use of hexane Gold Medal Award from the 10th International Warsaw In-as a solvent for extraction is vention Show” (IWIS 2016), Poland;restricted due to its toxicities. Special Award (on Stage) from the Malaysian Research &Therefore, the present studies Innovation Society, Malaysia;have focused on investigating Special Award from the Taiwan International Inventionthe use of vegetable oils as the Award Winners Association, Taiwan.alternative green solvents forextraction of chamuangonefrom G. cowa leaves. A nu-traceutical, soft gelatin cap-sule containing G. cowa leafextract (800 mg) extractedwith rice bran oil has beenprepared using a green ex-traction method. The extractsare standardized to contain1.9 mg/mL of chamuangone.The rice bran oil extract ofG. cowa leaves exhibitedsatisfactory anticanceractivities against humancolorectal adenocarcinoma,breast adenocarcinoma, andlung adenocarcinoma cellswith IC50 values of 12−16 µg/mL and no toxicity to normalcells. 93

50th Anniversary Prince of Songkla UniversityPreparation of a Mangosteen Fruit Pericarp Extract Containing α-man-gostin Made into a Formulation of a Gel for Treating Oral Mucositis Mangosteen pericarps are suitable solvent for extraction of assisted green extraction methoda by-product of the mangosteen (MAE). These solvents have similarjuice factory. The pericarp extracts α-mangostin. However, the use of polarities to dichloromethane, butare enriched in xanthones, particu- they are considered to be safer dichloromethane, which is a halo- and cheaper. The obtained extractslarly α-mangostin. This compound genated hydrocarbon as a solvent for extraction, is restricted due to contained α-mangostin of not lesshas been used as a marker for its toxicities. The absence of riskstandardization. Extracts from during extraction and the safety of than 2.0% w/w and can be usedmangosteen pericarps have been the ingredients used are a major directly for topical formulationsreported to have various phar- concern and have drawn attention without the rapid loss of solventmacological activities, including towards the need to use a greener by evaporation. This has resulted inantimicrobial, anti-inflammatory, solvent. The present studies have a reduced cost of production. Theantioxidant, and wound healing focused on investigating the use of medicinal creams and gels contain-properties, and has therefore topical excipients for the formula-been used in several commercial tion of a green product, that has ing 0.1−0.2% w/w of α-mangostinpharmaceutical products and cos- included isopropyl myristate andmetics. It has been reported that cetyl alcohol as alternative solvents were then formulated using thesedichloromethane was the most for extraction, using a microwave extracts.Award Gold Medal Award from the Brussels Innova Expo 2015, Belgium; Special Award “This is a Good Idea in 2015” from the Taiwan Prominent Inventor Association, Taiwan.94

Innovation for the MankindTopical Solution for Treatment of Skin Fungal InfectionMade from Rhinacanthus Nasutus Leaf Extract A leaf extract of Rhinacanthus na- An active constituent, rhina- sutus was prepared using an alternative canthin-C in the extract was green solvent and extraction method that standardized using an HPLC reduced toxic organic solvents previously method. The concentration of involved in the extraction process. The chlorophylls in the extract also obtained extract was used directly for decreased markedly compared topical formulations without requiring to the previous method. The evaporation of the solvent which re- topical antifungal solution sulted in a reduced cost for production. made from this extract con- taining rhinacanthin-C at aAward concentration of 0.1% w/v could be standardized in every Gold Medal Award from the 27th Interna- production batch. tional & Innovation Exhibition (ITEX 2016), Malaysia; and the Special Award from the World Invention Intellectual Property Association, Taiwan. 95

50th Anniversary Prince of Songkla University Assoc. Prof. Dr. Pharkphoom Panichayupakaranant E-mail: [email protected] Phytomedicine and Pharmaceutical Biotechnology Excellence Center 96

Innovation for the Mankind Our Research Series on Chronic Hepatitis Band the Application of Our Findings Hepatitis B virus (HBV) is important health problems in Thai- patients are chronically infectedone of the most important causes land. with mutant HBV. Our team didof acute hepatitis B in Asia, includ- First, I will describe the a pioneering study on the quanti-ing Thailand. Chronic hepatitis B, lengthy history of research projects fication of HBV envelope proteindefined as persistent HBV infection I have been involved in. I began (quantitative HBsAg) and reportedlonger than 6 months, is the most studying chronic hepatitis B in on the association of HBsAgcommon and important cause of 1996 and have been researching level with the phase of chronicliver cirrhosis and primary liver chronic hepatitis B with some of my hepatitis B infection and the riskcancer (i.e. hepatocellular carcino- colleagues for 20 years including of liver disease progression toma). Hepatocellular carcinoma is its prevalence, progression, treat- primary liver cancer. Quantitativethe sixth most common cancer in ment, prevention, and prognosis. HBsAg is also able to differenti-humans and is the leading cause of The following is a summary of our ate the mutant chronic hepatitiscancer deaths in Thai males. About most important findings. B from chronic inactive HBV.70−75% of primary liver cancers The prevalence of chronic HBsAg quantification is currentlyare caused by chronic hepatitis B. hepatitis B in Thailand is about approved and used worldwide.Chronic hepatitis B is, therefore, 3−5%. Among chronic hepatitisone of the most common and B Thai patients, 44−50% of the 97

50th Anniversary Prince of Songkla University Currently, there are two strategy accordingly. We call this of the Liver to urge the Worldstrategies of treatment for chronic type of approach the “road map Health Organization to establishhepatitis B, pegylated interferon concept”, which can reduce the “Hepatitis Day”, following whichwhich is a host immune modi- cost of treatment and has been the WHO announced that Julyfying agent, and nucleo(t)side adopted for clinical practice in 28th of every year will be Hepatitisanalogues which are inhibitors many countries in Asia. Day in order to create awarenessof HBV replication. We published I and some of the hepa- and to improve strategies for thetwo large clinical studies of pe- tologists in Southeast Asia did a prevention and treatment of viralgylated interferon treatment in cost-effectiveness analysis of the hepatitis.patients with chronic hepatitis B treatment of chronic hepatitis B Since 2010, our researchin the New England Journal of and collaborated with the Thai team has studied the use of HBVMedicine which is one of the top Ministry of Health to establish biomarkers such as HBsAg, HBVmedical journals. Based on these universal coverage for treatment DNA, HBeAg, and AntiHBe totwo studies, pegylated interferon of this disease for all Thai pa- predict liver disease progression,is now approved for treatment tients. I am also a core member risk of development of cirrhosisof chronic hepatitis B worldwide. of the Committee for Developing and/or primary liver cancer, andWe also reported on the factors a Guideline for the Treatment of their possible roles in predictingassociated with the response to Chronic Hepatitis B in the Asia treatment response and guidingpegylated interferon treatment. Pacific region. a treatment discontinuation de-The predictors of nonresponse to On a personal note, I was cision. HBV biomarkers can alsotreatment can be used as a stop- the president of the Asia Pacific be used to guide personalizedping rule in patients who do not Association for the Study of the therapy. We also did studies onrespond to treatment. The stop- Liver (APASL) in 2011. I joined using FibroScan® to measure liverping rule can reduce treatment the president of the American stiffness to evaluate the stage ofcosts and avoid treatment side Association for the Study of the liver fibrosis and cirrhosis withouteffects in non-responders. The Liver and the president of the Eu- requiring a liver biopsy.stopping rule is recommended in ropean Association for the Studymany international guidelines foroptimizing treatment strategy. We also researched severalpromising oral anti-HBV drugs inphase 1 to phase 3 studies untilsome of them were approved forclinical use. Based on our studyfindings in 2008, we proposed theoptimal use of an inexpensive drugas the initial drug for treatment ofpatients with chronic hepatitis B,which was able to achieve as goodoutcomes as more potent but moreexpensive drugs by monitoringHBV DNA during the treatmentand modifying the treatment98

Innovation for the Mankind Due to the complexicity of Our research team has also which have seen publication inHBV virus and its disease, our team done studies on other liver diseases well-known medical journals andcontinues doing both molecular such as chronic hepatitis C, liver whose findings have been appliedand clinical research in order to cancer, cirrhosis, and fatty liver. in clinical practice.better understand this serious Lastly, I would like to thankdisease, and help improve and all of my colleagues for theiroptimize the care of patients with great efforts and contributionschronic hepatitis B. in our ongoing research, many ofResearch Team 6. Dr. Jaksin Sottisuporn Asso. Prof. Teerha Piratvisuth, MD 7. Dr. Sawangpong Jandee E-mail: [email protected]. Assoc. Prof. Teerha Piratvisuth 8. Ms. Supannarangsri Pongpanit NKC Institute of Gastroenteroen-2. Assoc. Prof. Bancha Ovartlarnporn 9. Ms. Nuttina Wichaidit terology and Hepatology,3. Assist Prof. Naichaya Chamroonkul 10.Ms. Kitiya Kongthong Faculty of Medicine4. Assist Prof. Pimsiri Sripongpan5. Dr. Teepawit Witeerungrot 99

50th Anniversary Prince of Songkla University Lactobacillus paracasei SD1: A novel probiotic In Thailand, a report of the Ministry of Public Health, Thailand showed that approximately 60% of 3-year-old children were affected by dental caries, especially chil- dren in the southern part of Thai- land. Regional data in Songkhla Province confirmed the high rate of caries (71.2%) among Thai children in the South of Thailand. Dental caries is considered as a serious public-health problem, due to its impact on individuals and communities in terms of pain and suffering, impairment of function, and reduced quality of life. Despite great efforts and achievements in oral health promotion, dental caries remain as a major health problem among Thai children. A high burden is reported each year for treatment of the disease and its sequelae; thus, novel complemen- tary strategies are required for the prevention of caries.100

Innovation for the Mankind Probiotics have been proven A systemic review and meta-analysisto have benefits for prevention suggested that probiotics decreasedor treatment of gastrointestinal the mutans streptococci anddiseases. In recent years, an in- could have a positive effect in thecreased interest in probiotics for prevention of caries. However,oral health has emerged. The ef- those probiotic strains could not lastfects of probiotics have been pro- long in the oral cavity due to theirposed for the prevention of caries. non-oral origin. 101

50th Anniversary Prince of Songkla University A research team from the longer-term of 6 months of daily Assoc. Prof. Dr. Roongnapa SrichanaFaculty of Dentistry, Prince of probiotic ingestion significantly E-mail: [email protected] University conducted a reduced the number of MS and Drug Delivery System Excellence Center,screening to select potential probi- caries risk among the school chil- Faculty of Pharmaceutical Sciencesotic strains of Lactobacillus strains dren with a high number of caries.derived from caries-free subjects. It was also found that there wasIt demonstrated that Lactobacillus an increase of immune responseparacasei SD1 and Lactobacillus in saliva after receiving probioticrhamnosus SD11 exhibited good products. No adverse effect wasproperties (e.g., inhibiting growth observed in previous clinical trials,of oral pathogens by producing indicating the safety of the strains.antimicrobial substances against The study was further performedcariogenic bacteria and adhering in a small child developmentwell to human keratinocytes). Pro- center. A decrease of cariogenicbiotics were studied further in clin- bacteria was observed after re-ical trials to explore the effect on ceiving probiotics. All results haveprevention of caries and its safety. been accepted for publication in aIt was shown that at short-term, high quality international journal.a four-week consumption of milk Therefore, probiotics may be anproducts containing probiotics alternative way for the preventioncould reduce salivary cariogenic of dental caries in the community.bacteria in adult volunteers. A102

Innovation for the Mankind Rubber LatexAllergen Sensor Based onMolecularly Imprinted PolymersLatex allergens from the rub- and the proteins in rubber-based natural rubber latex was used as ber tree (Hevea brasiliensis) gloves. An adequately sensitive a template and imprinted in the cause severe and chronic al- detection method used by the cavities within the polymer matrix. lergies in health care workers and manufacturers of gloves would Upon removing the template the other sensitized persons. Allergic help reduce most latex allergens. molecule-imprinted cavity was reactions to components in latex This research work solves problems associated specifically with the rubber are a growing problem. for those who are allergic to rub- transformations and the config- Proteins on the surface of rubber ber or rubber latex products. urational changes of the proteins particles contain a number of epi- Molecularly imprinted in the binding cavities. Detection topes that bind to immunoglobu- polymers (MIPs) incorporated with of the allergen protein was per- lin E (IgE) and have immunological the detection unit can be used to formed using an imprinted surface cross-reactivities leading to the quantify the protein allergen. In layer combined with a quartz crys- allergenicity. Methods are needed the preparation process, a pro- tal microbalance transducer which to detect rubber latex proteins tein molecule isolated from the allowed label-free measurements. 103

50th Anniversary Prince of Songkla University We developed MIPs that pro- vided multiplex platforms for delivery104 of a rapid diagnosis of an allergy upon the presence of complex bioanalytes. The advantage of this technique is an ability to complement an analytical procedure to detect allergen proteins in real matrices obtained by extraction from rubber gloves, cosmetics, and oth- er products. The strategy of detection by the synthetic recognition system mimicked natural antibodies with the ability to attach to the allergen protein. This technology is feasible for scale-up and run as an on-line measurement. The technology can distinguish bind- ing sites by differentiating ligand species interactions with the biologi- cal recognition process. The template introduced through a mesoporous material leads to the enhanced surface interactions within a three-dimensional image of the molecular cavities. After template removal from the polymer with the established washing protocol, the obtained MIPs exhibited a high adsorption capacity for the target and efficient binding sites through which the MIPs could perform well. MIPs were developed by co- polymerization of suitable functional monomer(s) and cross-linking mono- mer following by washing the template molecule leaving the imprint on the polymeric matrix that made up the functional monomers by cross-linking networks. The selectivity of the MIPs by the present method was related to the binding template and the functional groups by hydrogen bond interactions and ionic interactions. The sensing element produced from MIPs showed a high recognition with good selectivity for the template.

Innovation for the Mankind An MIP with a lot of pores canallow for a higher rate of penetrationof the template. These MIPs are stillbarely scratching the surface of theirfull capabilities. They can also sensethe extracellular environments thatproduce the developmental signalsand improve the responses on thesensor layer. In addition, they can bedeveloped for techniques to screenpharmaceutical compounds in complexsamples. They can distinguish differentanalytes to precisely determine variousconcentrations of stereoisomers withand without the lipoprotein matrix.An MIP can establish a rapid analysis ofa target analyte. In addition, detailedexamination revealed by the surfacerearrangements in the presence of thetemplate were identified by AtomicForce Microscopy and the interactingof a specific protein receptor by Ra-man spectroscopy. Assoc. Prof. Dr. Roongnapa Srichana E-mail: [email protected] Drug Delivery System Excellence Center and NANOTEC-PSU Faculty of Pharmaceutical Sciences 105

50th Anniversary Prince of Songkla University Health and Health-care Systems in Southeast Asia : Diversity and Transitions Southeast Asia is a region of enormous social, economic, and political diversity, both across and within countries, shaped by its history, geography, and position as a major crossroad of trade and the movement of goods and services. These factors have not only contributed to the disparate health status of the region’s diverse populations, but also to the diverse nature of its health systems, which are at varying stages of evolution. Rapid but inequitable socioeconomic development, coupled with differing rates of demographic and epidemio- logical transitions, have accentuated health disparities and posed great public health challenges for national health systems, particularly the control of emerging infectious diseases and the rise of non-communica- ble diseases within ageing populations. While novel forms of health care are evolving in the region, such as corporatized public health-care systems (govern- ment owned, but operating according to corporate principles and with private-sector participation) and106

financing mechanisms to achieve Innovation for the Mankinduniversal coverage, there are keylessons for health reforms and 107decentralization. New challengeshave emerged with rising tradein health services, migration ofthe health workforce, and medi-cal tourism. Juxtaposed betweenthe emerging giant economies ofChina and India, countries of theregion are attempting to forge acommon regional identity, despitetheir diversity, to seek mutuallyacceptable and effective solutionsto key regional health challenges.In this first paper in the LancetSeries on health in Southeast Asia,we present an overview of keydemographic and epidemiologicalchanges in the region, explore chal-lenges facing health systems, anddraw attention to the potential forregional collaboration in health.Key messages • The diversity of geogra-phy and history, including social,cultural, and economic differenc-es, have contributed to highlydivergent health status and healthsystems across and within countriesof southeast Asia. • Demographic transitionis taking place at the fastest ratescompared with other regions ofthe world, whether in terms of fer-tility reductions, population age-ing, and rural-to-urban migration.Rapid epidemiological transitionis also occurring, with the diseaseburden shifting from infectious tochronic diseases.

50th Anniversary Prince of Songkla University • Rapid urbanization, population movement, and108 high-density living raise con- cerns about newly emerging infectious diseases, but these outbreaks have stimulated regional cooperation in infor- mation exchange and improve- ment in disease surveillance systems. • Southeast Asia’s pe- culiar geology contributes to being the most disaster-prone region in the world, more susceptible to natural and man-made disasters affecting health, including earthquakes, typhoons, floods, and envi- ronmental pollution. Climate change along with rapid eco- nomic development could exac- erbate the spread of emerging infectious diseases. • Health systems in the region are a dynamic mix of public and private delivery and financing, with new organizational forms such as corporatized public hospitals, and innovative service delivery responding to competitive pri- vate health-care markets and growing medical tourism. • The health-care sys- tems are highly diverse, rang- ing from dominant tax-based financing to social insurance and high out-of-pocket pay- ments across the region. There is a greater push for universal coverage of the population, but more needs to be done to ensure access to health services for the poor.

Prof. Dr. Virasakdi Chongsuvivatwong,MD Innovation for the MankindE-mail: [email protected] • Private health expen-Institute of Health Research and diture is increasing relativeDevelopment for the South (RDH) to government expenditure,Faculty of Medicine where new forms of financing include user charges, improved targeting of subsidies, and greater cost recovery. Health- care financing could be further restructured in response to future demographic shifts in age-dependency, as in intro- duction of medical savings and social insurance for long-term care. • There is potential for greater public-private partici- pation with economic growth through ASEAN integration and further regional health col- laboration despite the current division of the region under two WHO regional offices. Published in The Lancet Vol 377 January 29, 2011 pp 429-437 Researcher Team Kai Hong Phua Mui Teng Yap Nicola S Pocock Jamal H Hashim Rethy Chhem Siswanto Agus Wilopo Alan D Lopez 109

50th Anniversary Prince of Songkla University A Novel Treatment of Lung Tuberculosis by Inhalation“Tuberculosis is an infectious further research for a new lead patient contains Mycobacterium disease and has been a prob- or novel therapy. The researcher tuberculosis (Mtb). Mycobacteria lem in developing countries in PSU has looked for new strate- replicate and persist in the alveolar for half a century. The pharma- gies to fight lung tuberculosis for macrophages. ceutical industry in the developed over 10 years. The inhalation of world does not want to invest in small droplets from an active TB110

Innovation for the MankindStrategies for fighting lung tu-berculosis Since M. tuberculosis re-sides in the alveolar macrophages(AMs) we need to deliver a highconcentration of drug to the lung.Technology to target the AMs inthe lung with antituberculosisdrug therapy may shorten thecourse. Since the drug concen-tration would be much lower, itcan be envisaged that fewer sideeffects would be expected. It can be seen from theevidence below that an antituber-culosis drug that is encapsulatedin a liposome carrier can targetthe AMs. It shows clearly that thedrug can be taken up within twominutes. Phagocytosis of NR8383cells incubated with reconstitutedPZA proliposome formulation 1stained with Lumidot® 640 at (a–c)2 and (d–f) 30 min in a differentmode; (a and d) bright field, (band e) fluorescence and (c and f)overlay (bar = 50 μm) 111

50th Anniversary Prince of Songkla University All of the studied drugs were successfully prepared and characterized. The results of the aerosol parameters and the cytotoxicity profiles of the studied formulations were satisfactory. The studied formulations indicated no immunological responses and showed no acute or chronic toxicity in an animal model. Clinical trial phase I The cytokine levels indicated some irri- tation to the airways but the level is unlikely to provoke the immune systems. Normal liver enzymes were observed. The kidney function was normal. The respiratory system functioned nor- mally. No jaundice or any skin allergies were reported. Clinical trial phase II This is ongoing research and has not been concluded. There was evidence that the clinical symptoms (i.e. cough and hemorrhagic sputum) in patients with add-on antitubercu- losis inhalation were lower than the control standard therapy group. Assoc. Prof. Teerapol Srichana E-mail: [email protected] Drug Delivery System excellence Center, Faculty of Pharmaceutical Sciences112

Innovation for the Mankind Fabrication ofNovel Scaffolds asa Bone Substitute for Repairing Maxillofacial Bone Defects Several patients have bone morbidities in the maxillofa- cial region from some major causes including trauma, accident, tumor and cancer surgeries, and physiologic resorption in the elder- ly. Surgical reconstruction of those bone defects is essential to restore functions and improve quality of life of the patients. Up to now, the reconstructions using autogenous bone grafting from the iliac crest is the gold standard, but, harvest- ing of the bone graft requires more surgical sites that increase the patient’s morbidity. There- fore, xenogenic bovine bone and allogenic freeze-dried bone from other persons are often selected to replace the autogenous bone. 113

50th Anniversary Prince of Songkla University Our research team from the Cra- nio-Maxillofacial Hard Tissue Engineering Cen- ter (CTEC), Department of Oral and Maxillofa- cial Surgery, Faculty of Dentistry successfully developed two scaffolding techniques of Melt Stretching and Multilayer Deposition (MSMD) and modified Melt Stretching and Multilayer Deposition (mMSMD) or Melt Stretching and Compression Molding (MSCM). The techniques are filament-based processes that are easy and fast for fabrication of the scaffolds with appropriate properties to repair bone defects. Moreover, their costs of fabrication are re- markably less than the commercially available scaffolds that allow low-income patients to reach a higher standard of treatment. However, risks of transmitted dis- eases and the patient’s acceptance are the concerns. In addition, most of them are commercially imported with high costs that some patients cannot afford. For several years, using synthetic bone substitutes instead of the xenogenic bone has become more popular. Various techniques have been developed for scaffolding the proper bone substitutes; nevertheless, most of them still use solvents or porogens that may be toxic to the cells and tissue of the patients. Some comput- erized fabricating techniques that can make the scaffolds with uniform patterns are still very expensive.114

Innovation for the Mankind Both techniques use the folds can be made by arrangingmelt-blending process to fabricate the filaments on a poly-vinyl tem-polymeric composite monofila- plate in a grid pattern, and theirments without using any solvents contact points are then connect-or porogens; therefore, they are ed by stamping in warm water. Three-dimensional (3-D) scaffoldsconsidered clean. Poly (ε-capro- are made by depositing the mono- layer scaffolds and stamping. Thelactone) is a biomaterial used as processes of the MSCM techniquethe major component, while some are easier and more practical. Theother bioactive materials including 3-D scaffold is made by compress-hydroxyapatite, biphasic calcium ing the polymeric monofilamentphosphate and chitosan can be into a glass mold and immersingused as fillers. The composite in warm water. The technique ismonofilaments are made by melt- chairside fabrication that can being, extruding, and stretching and performed in a sterile condition.they can be stocked for furtheruse. The monolayer MSMD scaf- 115

50th Anniversary Prince of Songkla University The properties of both types of scaffolds have been intensively evaluated in vitro and in animal models. The results demonstrate that the scaffolds are biocompatible and they can enhance new bone regeneration. There are four main advantages of the filament-based scaffolds. 1. Several types of biomaterials can be used as the fillers; therefore, the properties of the composite scaffolds can be tailored. 2. The monofilaments can be stocked for various techniques of scaffolding including the two techniques as well as weaving techniques. 3. The monolayer scaffolds can be cut into various shapes. In addition, the scaffolds can be combined with CT-scan images and rapid prototyping models for constructing the 3-D scaffolds that fit the actual size of a bone defect. 4. Any oral surgeon, beside his dental chair, can quickly construct the MSCM scaffolds during an operation. Fabricating the 3-D scaffold within a glass mold is a closed, sterile environment that prevents contamination. Asst. Prof. Dr. Nuttawut Thuaksuban,DDS E-mail: [email protected] Cranio-Maxillofacial Hard Tissue Enigineering Center (CTEC) Faculty of Dentistry116

Innovation for the MankindUsing Teeth as Bone Grafting Materialfor Reconstructing Alveolar Bone Defects“To reconstruct alveolar bone substitution method was devel- and replace the scaffold without defects of jaw bone that oped to achieve the fundamental dimensional change of the recon- occur after tooth loss from bone substitution properties that struction site. various causes such as accidents, include (1) having osteoinductive Human teeth share a periodontal diseases or bone re- proteins which facilitate new bone similarity in organic and inorganic sorption in the elderly, autogenous formation, (2) having osteocon- composition as well as some bone grafting is the treatment duction characteristics that act as a osteoinductive proteins such as of choice. However, the major scaffold for neovascular ingrowth, bone. When teeth are removed drawbacks of autogenous bone adhesion, and proliferation of from the patient’s body, they are graft are the need for a second- osteoblastic cells, and (3) having considered as bio-medical waste ary surgical site that leads to the mineralization ability and bio- that needs proper management patient being uncomfortable and degradability at the proper time and disposal. experiencing pain. A novel bone so as to allow new bone to grow 117

50th Anniversary Prince of Songkla University Autologous demineralized tooth matrix (aDTM) is a bone sub- stitution material that is prepared and modified from the patient’s own nonfunctional tooth such as a wisdom tooth, non-occluded tooth or unrestorable tooth. Fol- lowing extraction, the soft tissues and crown restorations are re- moved before storing in a freezer at −20°C. After that the tooth is crushed into small particles, rang- ing from 0.5−1.0 mm. The particles are physico-chemically modified by reducing the mineral content, eliminating the fat, lyophilized, and sterilized before clinical use as a bone grafting material. aDTM is a bone substi- tution material that is provided by the patients. The fabrication creates an aDTM composed of hy- droxyapatite crystal that contains 37% calcium, 14% phosphorus, and the principal osteoinductive proteins. aDTM can also be pre- pared and kept for further alveolar bone augmentation. aDTM can be fabricated with a weight of 1.5−2.0 g depending on the size of the donor tooth and can be used as bone substitution in various jaw bone defects including alveolar ridge preservation after tooth extraction and peri-implant de- hiscence/fenestration defects. The clinical outcome of aDTM to bone augmentation is equivalent to the commercially imported bone sub- stitution in packages of 0.25−0.5 g prepared from bovine bone which has been used routinely for a long period but is quite expensive.118

Innovation for the Mankind In conclusion, aDTM is Assoc. Prof. Dr. Srisurang Suttapreyasri,DDSan autologous bone substitution E-mail: [email protected] that contains hydroxy- Warisa O uyyamwongs,apatite crystals similar to bone Monthira Saebeand also has osteoinductive pro- Cranio-Maxillofacial Hard Tissueteins that facilitate new bone Engineering Center,formation. The fabrication of Faculty of DentistryaDTM can be performed in-housewith basic equipment and chem- 119icals; therefore, the preparationcost is very low compared tothe commercially available bonegraft materials. aDTM has beenused in clinical applications anddemonstrates that it is an effi-cient and safe bone substitutionmaterial equally as good as thecommercially bovine-derivedbone substitution materials.

50th Anniversary Prince of Songkla University Gas Induced Superheated Slurry (GISS) Technology “ Gas induced superheated slurry (GISS) technology improves casting quality while reducing production costs at the same time. The technology employs the superheated slurry casting process which is the world’s latest metal casting innovation. The GISS technology is a quick solu- tion technology for aluminum die casters who have porosity defect problems that result in high reject rates. It is different from other solutions, such as vacuum assist and squeeze pins, because GISS technology also reduces production costs while reduc- ing the reject rates. Our customers are benefiting from significant cost reductions after applying the GISS technology.120

Innovation for the Mankind Besides improving thequality and reducing costs, theGISS technology also enables thedie casting of wrought aluminumalloys such as 6061, 6063, and 7075alloys, which can be anodized. Thisbreakthrough will open up severalopportunities in the die castingindustry. 121

50th Anniversary Prince of Songkla University Since the slurry is injected with a lower heat content with a controlled viscosity and some initial nuclei, we can achieve cost benefits immediately using the GISS technology. Some of the key benefits include reduced rejection rates due to the reductions in the gas and shrinkage porosities from 10–50% to 1–5%*. Other benefits are production costs that are reduced by 10–15%*, cycle time is reduced by 15–25%*, die life is increased by 2–4 times*, reduced amount of melting energy, reduced lubricant use, and a 15–30%* reduction in water treatment.122

Innovation for the Mankind GISS Technology wasofficially implemented in manycountries such as Japan, Singa-pore, India, China, Korea, Turkey,and Switzerland. Assoc. Prof. Dr. Jessada Wananasin E-mail: [email protected] Faculty of Engineering 123

50th Anniversary Prince of Songkla University Prototype of Liquid Filtration Systems for Consumption Quality “ Nowadays membrane technology is applied to eliminate undesirable particles that includes living and nonliving matter from liquids to improve the efficiency and quality of the media such as water quality, drinking water, and concentrated fruit juice including contamination by toxicants. In addition, membranes are also applied for removal of yeasts and suspended solids in fermented plant beverages (FPBs) for long term storage with good quality. Membrane filtration is a process that uses pressure to allow water or solute to pass through the pores of the membranes while dirty particles with sizes greater than the pore size cannot penetrate and remain on the membrane. This research produced a membrane microfiltration (MF) system from ceramic made from alumina as the main raw material which has an average pore size of 0.3 µm and can withstand pressures in the range of 20-80 psi. The prototypes of the ceramic MF were hol- low cylinders and the dimensions were 10-52 mm in diameter, 100-250 mm in length, and 3-10 mm in thickness. The cylinders were strong and of good quality with a smooth texture. The porosity of the prototype cylinders ranged from 48 to 55% and the pore sizes were 0.3-1 µm with the ability to remove pathogens, bacte- ria, suspended solids, and various contaminants from liquids such as water and FPBs.124

Innovation for the Mankind Researchers in our teamhad extended the ceramic mem-brane MF for practical use byplacing it within a PVC tube andhousing to form a module. Thisinvention with a single cylinder isgiven the name “Filter for removalparticles in water” (petty patentnumber 6092). In addition, theceramic materials with specificproperties inside the filtrationcylinder were also registered for apetty patent number 6642. Afterthat it was developed to havethree filter cylinders in one moduleto produce drinking water in ahousehold and also by increasingthe filter size and filtration toproduce potable water for acommunity. The ceramic MF hasalso been used for the removalof yeasts and suspended solids inFPB products. 125

50th Anniversary Prince of Songkla University content, pH, total acidity, elements including antibacterial and antioxidant activities of FSB before and after filtration including storage changed slightly (p > 0.05). The results of the sensory test using the Hedonic test found that all FPB products after filtration gave signifi- cantly higher scores (p < 0.05) in the overall acceptance than before filtration due to their greater clarity. The ceramic membrane filter was scaled up to have 3 filters in one module for use in small and medium-sized enterprises. The advantages of using the ceramic membrane are the fine texture with an average pore size of 0.3 µm and a long shelf life for 3-5 years. It is strong, easy to clean and operate, and is resistant to high acidity in FPB products including resistance to micro- bial degradation. In addition of filtration, it can be used to produce safe water, to treat wastewater, and in the beverage industry to produce fruit juices, wines, beers, and FPBs as well as probes for electrical devices and sensors. Hence, it has various applications related to filtration both in the community and industry. The principle of this filter module works Asst. Prof. Darunee Bhongsuwan by placing a ceramic filter(s) and housing inside E-mail: [email protected] of a PVC tube or stainless steel tube. The out- Assoc. Prof. Dr. Tripob Bhongsuwan, side tube has a connection for the inlet feed Assoc. Prof. Dr. Duangporn Kantachote, from a pump. This is ready for filtration with Nucharee Chomchoey and various applications such as water and FPBs as Mantana Boripan previously described. The use of microfiltration Faculty of Science ceramic membrane found that filtration re- moved all yeast from the fermented seaweed beverage (FSB) and no detection of yeast or foodborne pathogens throughout storage time for 6 months under room temperature. Total sugar, GABA (gamma-aminobutyric acid)126

Innovation for the Mankind Nano Cup & Smart White :Coating Innovation The binding of liquid on container surface involves directly withthe wettability and surface roughness. The researcher observed the liquid droplets on lotus leaves asthey form spheres. Such a container surface was designed based onliquid surface interaction for rubber latex cup innovation. 127

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Innovation for the MankindNano Cup The major pain in rubber From the laboratory to rubber Upstream of latex and its quali-plantations is the huge loss of plantation ficationfield latex during the harvesting Research on the latex re- After launching the Nanoprocess. Million of tons of latex pellent was patented in 2014. An cup, several tests of the quality ofhave been lost due to its sticky excellent implementation of the the field latex were demonstratednature. Natural rubber is used in research led to the award “Re- by the VFA value which was 10many applications and causes the search for Community” in 2014 times lower than anytime earlier.same pain from the view point of from Prince of Songkla University. Wonnatech Co.,Ltd. was sponsoredother industries. The result is a Wonnatech Co., Ltd. asked by the National Inovation Agencyloss of millions of Thai baht due to for permission to commercialize in the following year to increasethe lower quality of latex. Rubber the research and has launched a the production of Nano cups andpossesses a physical property that product called the “Nano cup” related chemical products. Whenis hard to overcome. It spreads out the project finished, the Nano cupall over the area of many kinds of was presented at an Exhibitionsubstrates. For each type of latex of SME innovations in Bangkokcollecting cup, the latex never and the use of the Nano cup wascompletely pours from the cup. demonstrated.There will always be about 2-5grams of dried rubber left behind Dr. Chalongrat Dangngamafter harvesting. The accumula- E-mail: [email protected] of dried rubber leads to the Faculty of Sciencecollection of dirt that affects thevolatile fatty acid (VFA) value. Thelatex turns bad in a relatively shorttime with a high VFA value. Low surface energy of thesurface is the key role. In order toobtain low suface energy the rightcombination of anions and cationshas been investigated. Subsequently, 60−65%of water in latex that includes30−35% of rubber particles andother substances has served asa repellent. The latex-repellentshould be coated properly on arough substrate with a low surfacetension. Dropping of the latexmust be greater than 160°. 129

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Innovation for the MankindSmart White A spray called Smart White at an angle of 150° or more upon From the lab to the marketis a perfect match for your white the substrate. The surface tension The superhydrophobicsneakers when wearing a dress of is now much lower than that of coating has been patented and theany color. No more worries and no water. A tilt of its substrate or an patent rights were transferred tomore dirty white shoes as long as extra force will easily initiate a Prince of Songkla University. Theyou keep Smart White with you slippery movement. Wonnatech Co., Ltd. has asked forat home, school, and office, and Under a combination of a permission to commercialize thein the park or camping. group of appropriate atoms with product. An up-scale productionMore than just waterproofing the chosen nanoparticles at the of superhydrophobic chemicals There are so many water- right time and concentrations of has begun to target those whiteproofing products in the market. all ingredients, the Smart White shoes or sneakers. Guaranteed byMore than just waterproofing is spray is produced. Coating the Regional and National Awards:a self-cleaning mechanism which materials with a very fine layer of 2016 MOST Innovation Awards,is desirable for most applications. the Smart White will behave like 2016 STSP Awards, and 7 Innova-Superhydrophobicity is the key. a lotus leaf. The appearance of a tion Awards 2017.Under superhydrophobic coating water drop on it is shown in theconditions, a drop of water forms picture above. Assoc. Prof. Dr. Nantakan Muensit E-mail: [email protected] Faculty of Science 131

50th Anniversary Prince of Songkla University Plant Root Camera PSU-ARDA Minirhizotron® Concept and design such as water and plant nutrients. This is bene- PSU-ARDA Minirhizotron® is a portable ficial for the management of fertilization and device for plant root study with a non-destruc- irrigation. The investigation of plant physiology tive method. Root dynamics (i.e. production, and plant pathology can be implemented by turnover, and lifespan) can be monitored this visualized system. repeatedly in the long-term. This leads to en- hancements by optimizing acquisitive resources132

Innovation for the MankindHOW TO USE For continuous in-situ rootmonitoring on living plants underfield conditions, a transparentacrylic tube is installed within thestudy site prior to the study of fineroot dynamics. A suitable lag isadvised before root observation iscommenced to allow for root den-sity equilibrium and root processat the soil-minirhizotron interface.The device is then inserted intothe transparent acrylic tube andthe camera can capture imagesquickly at the interval depths. Theacquired images can be recordedto folders and the root imagescan be analyzed with Root ImageAnalysis (RIA) software. 133

50th Anniversary Prince of Songkla University Novel benefits SPECIFICATIONS Assoc. Prof. Dr. Sayan Sdoodee PSU-ARDA Minirhizotron® Image resolution: 640 x 480 E-mail: [email protected] is a suitable device for in-situ Capture speed : 1.20 min/panel Faculty of Natural Resources plant root investigation especially Interface: USB root dynamics in agricultural and Power supply: Laptop/Portable battery natural agroforestry systems, and Software interface: RIA (Window 7/64 bit) can be operated under various soil Dimension: 10 cm diameter × 100 cm length conditions (e.g., paddy field, slope Weight: 1.5 kg area or flooded sites). Various Patented: 12535 benefits will be realized. - Optimizing water and nutrient use Award - Precise tracking of root develop- ment under various environmental Gold Medal, Leading Innovation conditions and Diploma from Kaohsiung - Field management plantations International Invention and and control of soil borne patho- Design EXPO 2015, Taiwan gens - Improving plant productivity - Integration on agricultural eco- system134

Innovation for the MankindBacillus subtilis Bio-Agent for Safe and Quality Vegetables Nowadays hydroponic vegetables have become one of the trends for clean food as Thai people become more concerned about exercis- ing, health, and a better lifestyle. We often see hydroponic vegetables in the supermarket at more affordable prices. Numerous hydroponic farm owners have increased public aware- ness by turning their farms into restaurants. Nevertheless the risk of chemical pesticides is one of the big problems in vegetable pro- duction and consumers are still asking for less harmful vegetables to serve as preventive medicines or functional food for a healthy life. 135

50th Anniversary Prince of Songkla University There is a growing concern about the safety of the hydroponic136 vegetable production process and yield. The researchers from the Faculty of Natural Resources, Faculty of Economics and National Biological Control Research Center, Southern Regional Center, Prince of Songkla University have invented a Bacillus subtilis bioagent (BSB) developed for chemical pesticide substitution which provides effective control of root rot and leaf spot diseases. These diseases are severe problems in all stages of hydroponic vegetable cultivation. The BSB contains the active ingredients of Bacillus sub- tilis Lpdd3-1 which is isolated from soil as effective bacteria for controlling root rot caused by Pythium spp. and leaf spot caused by Alternaria spp. BSB is stable for two years at room temperature. It is conveniently applied, provides economical benefits, promotes vegetable root system growth, in- creases disease resistance, without affecting nitrate accumulation to produce pathogen-free vegetables that stay crispy fresh for a long time, and without a bitter taste. The remaining nutrient solutions without contamination in the pro- duction system can be applied as a nutrient source for other plants. Thus, the residue fertilizer has no effect on the environment.

Innovation for the Mankind BSB was processed under BSB is an attractive bioagent fora reliable, systematic, academic hydroponic farmers in both theresearch program. Empirical accep- prevention and control of roottance was demonstrated from the rot and leaf spot. BSB had beennational and international awards. applied for hydroponic vegetableFrom the safe and efficient use production in all regions of Thai-since 2015 instead of pesticides, land. Assoc. Prof. Dr. Ashara Pengnoo E-mail: [email protected], [email protected] Dr. Chutharmard Kaewman, Asst. Prof. Sirirat kiatpathomchai, Ms. Prattana Attamanee and Mr. Pathompong Wonglieng Faculty of Natural Resources 137

50th Anniversary Prince of Songkla University Zinc Field Test Kit to Improve Rice Quality and Increase Rice Yield“Rice is a significant economic crop of Thailand and around on the use of chemical fertilizers enzymes involved in metabolic ac- half of Thailand’s cultivated that result in high costs to farmers. tivities in both photosynthesis and Although chemical fertilizers can conversion of sugars to starch, asland is used for rice plantations. enhance rice growth, prolonged well as in the resistance to infec-However, the average rice yield and excessive usage can negatively tion by certain pathogens. Whenper rai (Thai unit of measurement affect soil fertility. Another issue zinc is inadequate, rice yields areequivalent to 0.16 hectare) in Thai- that is often overlooked by farmers reduced and the quality of riceland is very low. The conventional is zinc deficiency. Zinc is a major grains is frequently impaired.technique to improve yields relies component and activator of several138

Innovation for the Mankind One cause of zinc deficien- rice plants. When zinc deficiency with zinc deficiency have impairedcy in rice plantations is negligence occurs, rice yields are reduced immune systems and pregnantto re-add zinc to soil after many and their quality is also impaired. women with zinc deficiency areharvest cycles. Prolonged use of In cases of severe zinc deficiency, at a higher risk for both delayedNPK fertilizer can also be another growth of the rice plant is stunted physical and mental developmentfactor of zinc deficiency since it and the leaves are visibly twisted of the fetus. Therefore, zinc levelincreases the concentrations of and ragged. A zinc deficiency in monitoring with a zinc-soil testsoluble phosphorus and bicar- soil also results in zinc deficiency kit is very important and hasbonate ions, which chelate zinc in rice grains, which directly affects wide-ranging implications andand reduce its bioavailability to the health of consumers. Children effects. 139

50th Anniversary Prince of Songkla University Through the combined use of the zinc-soil test kit and bio- zinc fertilizers, plans to restore soil quality can be effectively and efficiently implemented. This will result in a better quality of rice and therefore increase the rice yields. Our knowledge has been trans- ferred to domestic farmers over 65 times and it has been utilized in rice plantations in 17 provinces of Thailand.140

Innovation for the Mankind“ In addition, this research work was officially licensed and commercialized by MSO Bio Industry Co., Ltd., (IP numbers 7073, 10373 and 1301004967) on March 28, 2015 for a period of five years. MSO Bio Industry Co., Ltd. is selling the kit both domestically and internationally.Highlights of the zinc-soil test kit are:It is the world’s first zinc-soil test kit that can be exported to agri- Asst. Prof. Dr. Warakorn Limbutcultural countries such as Indonesia, Malaysia, Philippines, Vietnam, E-mail: [email protected], India, and Pakistan. Asst. Prof. Adul Tiengchanya,Since it is made in Thailand, it is inexpensive and reduces expensive Assoc. Prof. Dr. Proespichayaimports from overseas. Kanatharan,It is easy to use as it is portable and it gives fast results that are easy Assoc. Prof. Dr. Panote Thavarungkulto interpret. and Dr. Klairung SamartIt is environmentally friendly with non-toxic reagents. Faculty of ScienceIt gives a qualitative analysis for zinc at different concentrationswithout the need of a calibration curve.It is highly accurate compared with the standard method (InductivelyCoupled Plasma–Optical Emission Spectrometer, ICP-OES).After zinc deficiency occurs, farmers can improve soils by using bio-zinc fertilizer to restore the soil quality. This will result in better ricequality, increased rice yields, and reduced cost of rice production.The kit Increases the self-esteem of Thai farmers and they becomeself-reliant in using the zinc-soil test kit. It also empowers them tosolve problems on their own.The kit can be manufactured cheaply using commonly availableinstruments. 141