Recent Patents on Biomedical Engineering (v.4, #3)

A Novel Method for Screening of Anti-Cancer Drugs: Availability of Screening in Acidic Medium by Toshihiko Fukamachi, Hiromi Saito, Hiroshi Kobayashi (141-152).
The inside of the human body is maintained within a narrow pH range around 7.4, but cancer nests are acidified,mainly due to insufficient blood circulation and impaired respiration. The activities of all enzymes are strictly dependenton pH, and hence many metabolic processes catalyzed by the pH-dependent enzymes decline as pH decreases insuch acidified diseased areas, leading us to argue that the efficacy of inhibitors varies under different pH conditions.However, there have been few reports to examine inhibitor efficacy in acidic conditions. The main reason for this insufficientinvestigation may be that no reliable method for the screening of such medicines has been developed. Our group hasinvented a useful method for this purpose, and has found that several medicines have high efficacy as anti-cancer reagentsunder acidic conditions. In this article, we introduce this novel method applied for a patent and recent findings that encourageus to use this simple method for developing new anti-cancer drugs.

Current Patents on Osteoinductive Molecules for Bone Tissue Engineering by Kevin W.H. Lo, Bret D. Ulery, Meng Deng, Keshia M. Ashe, Cato T. Laurencin (153-167).
Bone formation via osteoinductive molecules is an established and promising approach for musculoskeletal regenerativetherapies. Bone tissue engineering utilizing biocompatible scaffolds with osteoinductive molecules offers anovel therapeutic strategy for the treatment of bone defects and diseases. Currently, bone morphogenetic proteins (BMPs)and parathyroid hormone (PTH) are the only FDA-approved protein-based osteoinductive molecules. Since their approval,millions of patients worldwide have been treated with these protein-based medications. A large number of osteoinductivemolecules have been recently discovered and patented due to the need for effective and affordable therapeutic strategiesfor the treatment of musculoskeletal disorders. The authors take this opportunity to review the osteoinductive moleculepatent literature paying specific attention to molecular biology, current clinical applications, and future prospects.

Novel Polymer-Ceramics for Bone Repair and Regeneration by Meng Deng, Sangamesh G. Kumbar, Kevin W.-H. Lo, Bret D. Ulery, Cato T. Laurencin (168-184).
Bone is composed primarily of an inorganic mineral phase of calcium phosphate and an organic phase of collagen.Reconstruction of large bone defects resulting from trauma, pathological degeneration, or congenital deformity is asignificant medical challenge. Due to the limited availability and potential immunogenicity associated with autografts andallografts, tissue engineering has emerged as an alternative strategy to repair, restore, and regenerate lost or damaged tissuesusing biomaterials, cells, and factors alone or in combination. Polymers, ceramics, and their composites have beenwidely investigated as biomaterials for the development of synthetic bone graft substitutes. Specifically composites ofbiodegradable polymers and bioactive ceramics are attractive candidates that closely match the desirable properties of anautograft tissue (e.g. osteoconductivity and osteoinductivity). Composites can be fabricated into a variety of threedimensional(3D) porous structures or matrices to encourage bone regeneration. They can be further enhanced by incorporationof various factors or cells to promote bone healing. Recent advances in nanotechnology have allowed for the fabricationof nanocomposites in the form of particles or nanofibers that mimic the hierarchical arrangement of native bone.Present review focuses on bone repair/regeneration strategies using polymer-ceramic composites and highlights some ofthe recent important patents in the areas of tissue engineering and orthopedic devices. A basic overview of the physicochemical,structural and biological elements of bone is described to provide design considerations for clinically viablebone graft substitutes. Challenges in the development of tissue-inducing materials capable of eliciting precise control overcellular functions are also discussed.

This paper presents and discusses a number of significant seminal patents on surgical correction of myopia, hyperopiaand presbyopia. These patents essentially describe the devices and systems proposed to correct vision in the senseof ability for correct focusing on an image by correcting the eye length and the corneal curvature. In these developmentsthe pioneering works of Helmholtz (Near Vision Accommodation Theory), Schachar (SASI, Schachar AccommodativeScleral Implant), Silvestrinin (INTACS, Keravision, intrastromal corneal ring (ICR)), Hood and Mendez (CK, ConductiveKeratoplasty) and Shahinppor, Soltanpour and Shahinpoor (Active Scleral Bands, Bionic Vision) have been acknowledgedand reported. Discussed are also surgical corrections of human eye refractive errors such as presbyopia, hyperopia,myopia, and astigmatism by using transcutaneously inductively energized artificial muscle implants to actively change theaxial length and the corneal curvatures of the eye globe (active scleral bands) to correct vision refractive errors. Furtherbriefly reviewed are active, electrically controllable and implantable artificial muscle systems that can be used in suchsurgical corrections. These polymeric artificial muscles can be integrated with or sutured to the body organs and tissues.In particular, they can be sutured to the body tissues and organs as implants to be transcutaneously inductively energizedto actuate. These implants can induce enough accommodation of a few diopters, to correct presbyopia, hyperopia, andmyopia on demand. In some preferred patent embodiments, the implant comprises an active sphinctering smart band toencircle the sclera, preferably implanted under the conjunctiva and under the extraocular muscles to uniformly constrictthe eye globe, similar to a scleral buckle band for surgical correction of retinal detachment, to induce active temporarymyopia (hyperopia) by increasing (decreasing) the active length of the globe. In another embodiment, multiple and speciallydesigned constrictor bands can be used to enable surgeons to correct astigmatism. This review does not review thepatents in connection with LASIK (Laser-Assisted in Situ Keratomileusis) and Excimer laser, as there are many reviewsavailable on such developments. However, the pioneering works of Blum, Srinivasan and Wynne (Excimer Laser, AblativePhotodecomposition (APD), (US Patent 4,784,135, issued November 15, 1988)) and Professor Ioannis Pallikaris ofUniversity of Crete, Greece who was a pioneer in performing initial LASIK surgery should be acknowledged.

Recent Advancements in Ligament Replacement by Emmanuel C. Ekwueme, Albert L. Kwansa, Kevin Sharif, Saadiq F. El-Amin, Joseph W. Freeman (196-204).
The anterior cruciate ligament (ACL) is important for knee stability and kinematics. It is also the most commonlyinjured ligament of the knee and due to its poor healing potential, severe damage warrants surgical intervention includingcomplete replacement. Therefore, investigators have begun to pursue new techniques and devices for the repair,regeneration, and replacement of the ACL. These options involve the use of mechanically functional grafts that aredesigned to increase implant stability in order to withstand normal mechanical loads (while promoting ligament developmentin some cases). This article presents background on the ACL and its replacement, novel replacement approachesutilizing a variety of materials, and recent patent coverage.

Patent Selections: by Bentham Science Publishers (205-206).
The patents annotated in this section have been selected from various patent databases. These recent patents are relevant tothe articles published in this journal issue, categorized by medical imaging, bioinformatics, image processing, biomaterials,pharmaceutical drugs, bioengineering, medical devices, design, biological devices, biomechanics & diagnostic devices relatedto biomedical engineering.