Research

Injectable antibiotics loaded  bone substitute

Bone substitutes (BGS) are being increasingly used in surgery as over two millions bone grafting procedures are performed worldwide per year. The field of bone grafts and substitutes is among the most promising markets in the orthopedic industry. In clinical practice, preformed bone substitute is brittle so that hard formed according to the required implant materials. In addition, osteomyelitis is commonly seen associated with traumatic open bone wounds, post-operatively after orthopedic procedures such as bone fracture repair. The course of osteomyelitis treatment is a long-term and inconvenient procedure for patients, usually need antibiotic therapy for 6∼8 weeks. In the current study, we try to develop an injectable antibiotics-loaded bone substitute for bone grafting and preventing osteomyelitis. Currently, an injectable oxidized hyaluronic acid/adipic acid dihydrazide hydrogel (oxi-HA/ADH hydrogel) has been developed as a carrier, which can transform from liquid into a gel-like matrix within 3–8 min at body temperature. The antibiotics and osteoconductive calcium phosphate particles can be added into the hydrogel to form a bone substitute, which can effectively repair the bone defect and prevent osteomyelitis.

Intervertebral disc regeneration

Encapsulation of nucleus pulposus (NP) cells within in situ forming hydrogels is a novel biological treatment for early stage intervertebral disc degeneration. The procedure aims to prolong the life of the degenerating discs and to regenerate damaged tissue. In this study we developed an injectable oxidized hyaluronic acid–gelatin–adipic acid dihydrazide (oxi-HAG–ADH) hydrogel. High molecular weight (1900 kDa) hyaluronic acid was crosslinked with various concentrations of gelatin to synthesize the hydrogels and their viscoelastic properties were analyzed. Interactions between the hydrogels, NP cells, and the extracellular matrix (ECM) were also evaluated, as were the effects of the hydrogels on NP cell gene expression. The hydrogels possess several clinical advantages, including sterilizability, low viscosity for injection, and ease of use. The viscoelastic properties of the hydrogels were similar to native tissue, as reflected in the complex shear modulus (11–14 kPa for hydrogels, 11.3 kPa for native NP). Cultured NP cells not only attached to the hydrogels but also survived, proliferated, and maintained their round morphology. Importantly, we found that hydrogels increased NP cell expression of several crucial ECMrelated genes, such as COL2A1, AGN, SOX-9, and HIF-1A.

Ocular irrigating solution

Irrigation solution is widely used in intraocular surgical procedures, such as phacoemulsification, vitrectomy surgery and glaucoma surgery. Phacoemulsification is a surgery to remove the lens of the eye that has developed an opacification, which is referred to as a cataract, vitrectomy is a surgery to remove some or all of the vitreous humor from the eye, and glaucoma surgery is associated with laser treatment or making a cut in the eye in order to reduce the intraocular pressure (IOP). In Taiwan, according to the report of national health insurance department, there are an estimated 150,000 ocular surgical procedures were performed annually. The effect of intraocular surgery is related to the irrigation solution. An improper irrigation solution might damage to the cornea or lens, result in poor vision, blind spots, and even loss of vision. 

In this study, An ophthalmic irrigating solution in an amount sufficient to irrigate ocular tissues of a patient comprising: a) gamma-polyglutamic acid (gamma-PGA) and/or salt thereof in an amount effective to increase the viscosity of the solution; and b) an ophthalmically acceptable aqueous vehicle for the gamma-PGA and/or salt thereof for use in irrigating ocular tissues of a patient is disclosed. Also disclosed are an ophthalmic irrigating solution and a pharmaceutical kit for use in reducing stress-induced damage to ocular tissues of a patient during eye surgery. 

Patent: 

Gamma-polyglutamic acid-based ocular irrigating solutions

I483639, Taiwan

CA 2794563, Canada

AU 2011215775, Australia                   

Antibiotics loaded Biphasic Calcium Phosphate Cement 

Osteomyelitis therapy is a long-term and inconvenient procedure for a patient. Antibiotic-loaded bone cements are both a complementary and alternative treatment option to intravenous antibiotic therapy for the treatment of osteomyelitis. In the current study, the biphasic calciumphosphate cement (CPC), called 𝛼-TCP/HAP (𝛼-tricalciumphosphate/hydroxyapatite) biphasic cement, was prepared as an antibiotics carrier for osteomyelitis. The developed biphasic cement with a microstructure of 𝛼-TCP surrounding the HAP has a fast setting time which will fulfill the clinical demand. The X-ray diffraction and Fourier transform infrared spectrometry analyses showed the final phase to beHAP, the basic bone mineral, after setting for a period of time. Scanning electron microscopy revealed a porous structurewith particle sizes of a fewmicrometers.The addition of gentamicin in 𝛼-TCP/HAP would delay the transition of 𝛼-TCP but would not change the final-phase HAP. The gentamicin-loaded 𝛼-TCP/HAP supplies high doses of the antibiotic during the initial 24 hours when they are soaked in phosphate buffer solution (PBS). Thereafter, a slower drug release is produced, supplying minimum inhibitory concentration until the end of the experiment (30 days). Studies of growth inhibition of Staphylococcus aureus and Pseudomonas aeruginosa in culture indicated that gentamicin released after 30 days from 𝛼-TCP/HAP biphasic cement retained antibacterial activity.