Werner, Sabine, and Richard Grose. Regulation of Wound Healing by Growth Factors and Cytokines. Physiol Rev 83: 835–870, 2003; 10.1152/physrev.00032.2002.—Cutaneous wound healing is a complex proce...

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Regulation of Wound Healing by Growth Factors and Cytokines

This review focuses on calcium phosphate-based bone substitute materials that are used (or can be used) for teeth or bone replacement, bone repair, augmentation, or regeneration. This review will also include some properties of bone (e.g., interconnected porosity, biodegradability, bioactivity, osteoconductivity) that are being mimicked in the manufacture of calcium phosphate-based biomaterials and some of the reported factors and strategies that can make the calcium phosphate-based biomaterials acquire osteoinductive properties. Archaeological findings showed that attempts to replace missing teeth date back to the prehistoric period. The materials used then included shells, corals, ivory (from elephant tusks), metals, and human (from corpses) and animal bones. Because of the practice of cremation in many societies, not much is known about prehistoric materials used to replace bones lost to accident or disease. Presently, autografts (bones obtained from another anatomic site in the same subject) remain the gold standard for bone repair, substitution, and augmentation followed by allografts (bones from another subject, such as processed cadaver bones). Autografts and allografts while having the important advantage of being osteogenic or osteoinductive (i.e., inducing bone formation), suffer from several disadvantages. With autografts the drawbacks include additional expense and trauma to the patient, possibility of donor site morbidity, and limited availability. In the case of allografts, in addition to limited supply and high cost, potential viral transmission and immunogenicity are of serious concern. Because of the high cost and limited availability of autografts and allografts, there is a great need to develop synthetic alternative biomaterials for bone replacement, repair, and augmentation. Current commercial substitute materials to replace or repair teeth and bones include metals, polymers (natural or synthetic), corals, human bones (processed cadaver bones), animal bones (processed cow bones), corals and coral derived, synthetic ceramics (calcium phosphates, calcium sulfates, calcium carbonate, bioactive glasses), and composites. It is interesting to note that several of the materials used in prehistoric times are similar to the materials used presently (e.g., coral and coral derived, animal bone derived, metals). Generally, depending on the ability to stimulate bone tissue, materials for tooth or bone repair or replacement are classified as bioinert or bioactive. Bioinert materials do not stimulate bone formation but instead stimulate formation of fibrous tissue and therefore do not directly bond to bone and thus form a weak biomaterial-bone interface. Bioactive materials stimulate bone tissue formation and therefore directly bond with bone and thus form a uniquely strong biomaterial-bone interface. Bioinert materials include metals (e.g., titanium or titanium alloys, stainless steel, cobalt-chromium, Co-Cr, alloys), some synthetic polymers (e.g., PEEK, Teflon-type), and some ceramics (e.g., alumina, * To whom correspondence should be addressed. Phone: (212) 998-9580. Fax: (212) 995-4244. E-mail: rzl1@nyu.edu. Racquel Zapanta LeGeros received her Ph.D. degree from New York University. She is currently a Professor and Associate Chair of the Department of Biomaterials and Biomimetics at New York University College of Dentistry. Her pioneering work was on substitution in the apatite structure and effect on properties. Her research interests includes biologic and synthetic apatites and related calcium phosphates, calcium phosphatebased biomaterials in the form of granules, scaffolds, cements, and coatings, and implant surface modifications. Her current research is on the development of calcium phosphate-based biomaterial for prevention of bone loss induced by diseases (e.g., osteoporosis), therapy (e.g., radiation), condition (e.g., mineral deficiency, immobility), and recovery of bone loss. She is married to Dr. John P. LeGeros and mother of Bernard, David, Katherine, and Alessandra. Chem. Rev. 2008, 108, 4742–4753 4742

Calcium phosphate-based osteoinductive materials.

Bioceramics of calcium orthophosphates

https://www.jidonline.org/article/S0022-202X(15)33382-0/pdf

Keratinocyte–Fibroblast Interactions in Wound Healing

Adult bone marrow derived mesenchymal stem cells offer the potential to open a new frontier in medicine. Regenerative medicine aims to replace effete cells in a broad range of conditions associated with damaged cartilage, bone, muscle, tendon and ligament. However the normal process of immune rejection of mismatched allogeneic tissue would appear to prevent the realisation of such ambitions. In fact mesenchymal stem cells avoid allogeneic rejection in humans and in animal models. These finding are supported by in vitro co-culture studies. Three broad mechanisms contribute to this effect. Firstly, mesenchymal stem cells are hypoimmunogenic, often lacking MHC-II and costimulatory molecule expression. Secondly, these stem cells prevent T cell responses indirectly through modulation of dendritic cells and directly by disrupting NK as well as CD8+ and CD4+ T cell function. Thirdly, mesenchymal stem cells induce a suppressive local microenvironment through the production of prostaglandins and interleukin-10 as well as by the expression of indoleamine 2,3,-dioxygenase, which depletes the local milieu of tryptophan. Comparison is made to maternal tolerance of the fetal allograft, and contrasted with the immune evasion mechanisms of tumor cells. Mesenchymal stem cells are a highly regulated self-renewing population of cells with potent mechanisms to avoid allogeneic rejection.

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Mesenchymal stem cells avoid allogeneic rejection

For surgical treatment of malignant tumors, it is important to clarify the depth and area of invasion of tumors and the relation to surrounding normal tissues such as adipose tissue, muscles and bones in addition to the histological diagnosis of the tumors before operation. For this purpose we clinically evaluated a magnetic resonance imaging (MRI) for diagnosing skin tumors. A MRI, SIGNA (GE), whic analyzes the tumors by a spin echo method (TR 1500, TE 20) was used in this study, and 29 slices of MRI in a tumor were accumulated crossing those tumors. The usefulness of three dimensional presentation of skin tumors performed by the MRI data was also discussed. For three dimensional presentation, VoxelflingerTM was applied and those images were compared with cross section of those tumors during operation and histological specimens. We applied the MRI examination on patients with malignant melanoma, malignant fibrous histiocytoma, fibrosarcoma and squamous cell carcinoma of skin.The MRI was a very useful tool to clarify the depth and area of invasion of malignant tumors and the relation to surrounding normal tissues. The effects of MRI was most remarkable when applied onpatients with malignant melanoma of soles. Three dimensional presentation obtained from the MRI data was also useful to know three dimensional condition of those tumors but it seems still to have limitation because of the analytical software of the computer. In conclusion, we suggest that MRI should be the imaging modality of choice in evaluating skin tumors especially of the extremities, and three-dimensional analysis will be beneficial as well as that of using slice images in the future.

Examination of diagnostic significance of MRI for skin malignant tumor.

The purpose of the present invention is to solve the problems of microneedles of the prior art, and provide a microneedle with improved penetration and shape-retention properties. This conical microneedle (10) comprises a tip part (2) that includes a drug and a biodegradable polymer, and a base part (4) that does not include a drug, wherein the tip (1) side is formed as a tip-reinforced area (6), the base (3) side adjoining the tip-reinforced area (6) is formed as a non-reinforced area (7), and the hardness of the tip-reinforced area (6) is higher than the hardness of the non-reinforced area (7). Microneedle patches equipped with the microneedle (10) of the present invention can reduce the pressing strength required when applied to a patient, alleviating the pain and fear experienced by the patient.

Microneedle and method for producing same

Analysis of 44 patients with malignant melanoma on whom sentinel lymph node biopsy was performed using the technique of blue dye and radioisotope

PROBLEM TO BE SOLVED: To provide a device having high operability for stably puncturing a microneedle in a skin.SOLUTION: An impact-application-type applicator 1 for microneedle patches for sticking a microneedle patch to a skin, includes a body 5, a spring extension/retraction lever 7, an elastic body 9, a stop mechanism 11, and an implantation switch 13. The spring extension/retraction lever is movably mounted on the body, and a microneedle patch can be installed on a tip thereof. The elastic body is a member for applying energizing force to the spring extension/retraction lever. The stop mechanism stops the spring extension/retraction lever in a state where the energizing force of the elastic body is worked on the body. The implantation switch is a member for releasing the engagement between the stop mechanism and the spring extension/retraction lever. The energizing force application mechanism further applies energizing force to the spring extension/retraction lever, with the microneedle patch pressed against the skin, by moving the spring extension/retraction lever to the tip side of the body.SELECTED DRAWING: Figure 2

Impact-application-type applicator for microneedle patch and tip member

마이크로 니들을 피부에 천자하기 위한 디바이스의 조작성을 향상시킴으로써, 약제의 진피 내에 대한 안정 투여를 실현한다. 마이크로 니들 패치용 임팩트 부가형 어플리케이터(1)는, 마이크로 니들 패치(3)를 피부에 붙이기 위한 어플리케이터로서, 본체(5); 스프링 신축 레버(7); 탄성체(9); 멈춤 기구(11); 찔러넣기 스위치(13);를 구비하고 있다. 스프링 신축 레버(7)는, 본체(5)에 대해 이동 가능하게 장착되고, 선단에 마이크로 니들 패치(3)를 장착 가능하다. 탄성체(9)는, 스프링 신축 레버(7)에 힘부여력을 부여하기 위한 부재이다. 멈춤 기구(11)는, 본체(5)에 대해 탄성체(9)의 힘부여력을 작용시키는 상태로 스프링 신축 레버(7)를 멈추게 하기 위한 기구이다. 찔러넣기 스위치(13)는, 멈춤 기구(11)와 스프링 신축 레버(7)의 계합을 해제하기 위한 부재이다. 또한, 힘부여력 부여기구(121)는, 스프링 신축 레버(7)가 본체(5)의 선단측으로 이동하는 것에 의해 마이크로 니들 패치(3)가 피부에 밀어붙여진 상태로, 추가로 스프링 신축 레버(7)에 힘부여력을 부여한다.

Ichiro Ono

Papers

Examination of diagnostic significance of MRI for skin malignant tumor.

Microneedle and method for producing same

Analysis of 44 patients with malignant melanoma on whom sentinel lymph node biopsy was performed using the technique of blue dye and radioisotope

Impact-application-type applicator for microneedle patch and tip member

마이크로 니들 패치용 임팩트 부가형 어플리케이터 및 선단 부재