Erica J. Carbone, Komal Rajpura, T. Jiang, C. Laurencin, K. W. Lo
Stimulation of bone formation using recombinant growth factors has been a promising strategy for bone repair and regeneration. However, small molecules have been suggested as alternatives to recombinant protein-based treatments because of their unique advantages. To date, therapeutic methods for orthopaedic applications still heavily rely on therapeutic protein-based growth factors. This trend is likely to be reversed since innovative drug discovery strategies, such as broad-spectrum database analysis and high throughput functional screens, have led to the discovery of many novel small molecule compounds and the development of novel applications of existing approved small molecule compounds. It should be noted that some of these small molecules with osteoinductive potential have been approved for human use due to their efficacy in treating other health ailments. Thus, these approved small molecule compounds are highly translatable to orthopaedic applications. In this article, we review the literature, paying attention to the prospects of existing approved small molecule therapeutics with bone regenerative capacity. Future directions of bone repair and regeneration using these approved small molecule drugs will be discussed as well.
{"title":"Regulation of bone regeneration with approved small molecule compounds","authors":"Erica J. Carbone, Komal Rajpura, T. Jiang, C. Laurencin, K. W. Lo","doi":"10.3402/arb.v1.25276","DOIUrl":"https://doi.org/10.3402/arb.v1.25276","url":null,"abstract":"Stimulation of bone formation using recombinant growth factors has been a promising strategy for bone repair and regeneration. However, small molecules have been suggested as alternatives to recombinant protein-based treatments because of their unique advantages. To date, therapeutic methods for orthopaedic applications still heavily rely on therapeutic protein-based growth factors. This trend is likely to be reversed since innovative drug discovery strategies, such as broad-spectrum database analysis and high throughput functional screens, have led to the discovery of many novel small molecule compounds and the development of novel applications of existing approved small molecule compounds. It should be noted that some of these small molecules with osteoinductive potential have been approved for human use due to their efficacy in treating other health ailments. Thus, these approved small molecule compounds are highly translatable to orthopaedic applications. In this article, we review the literature, paying attention to the prospects of existing approved small molecule therapeutics with bone regenerative capacity. Future directions of bone repair and regeneration using these approved small molecule drugs will be discussed as well.","PeriodicalId":269533,"journal":{"name":"Advances in Regenerative Biology","volume":"70 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131935718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angiogenesis, the process where new blood vessels form from existing vasculature, is essential for the successful integration of most tissue-engineered constructs and is dysregulated in many diseases, including cancer. To be functional, the newly formed vasculature must have similar structure and integrity as existing blood vessels, both of which are dependent upon mechanical and chemical cues from the surrounding extracellular matrix (ECM). ECM stiffness has emerged as a critical extracellular parameter that can modulate capillary network formation and barrier integrity. Moreover, matrix stiffness can alter how endothelial cells respond to soluble, angiogenic factors released by stromal cells, such as vascular endothelial growth factor (VEGF). In this review, we will discuss how matrix stiffness can affect the formation and structure of angiogenic vessels, and we will highlight the role of this work in the development of therapeutics to treat angiogenesis in cancer. Knowledge of the governing parameters for vessel formation is critical to the intelligent design of materials made to foster blood vessel growth for tissue-engineering applications and pharmaceuticals designed to intervene with newly formed vasculature in diseased tissue.
{"title":"Matrix stiffening in the formation of blood vessels","authors":"Danielle J. LaValley, C. Reinhart-King","doi":"10.3402/arb.v1.25247","DOIUrl":"https://doi.org/10.3402/arb.v1.25247","url":null,"abstract":"Angiogenesis, the process where new blood vessels form from existing vasculature, is essential for the successful integration of most tissue-engineered constructs and is dysregulated in many diseases, including cancer. To be functional, the newly formed vasculature must have similar structure and integrity as existing blood vessels, both of which are dependent upon mechanical and chemical cues from the surrounding extracellular matrix (ECM). ECM stiffness has emerged as a critical extracellular parameter that can modulate capillary network formation and barrier integrity. Moreover, matrix stiffness can alter how endothelial cells respond to soluble, angiogenic factors released by stromal cells, such as vascular endothelial growth factor (VEGF). In this review, we will discuss how matrix stiffness can affect the formation and structure of angiogenic vessels, and we will highlight the role of this work in the development of therapeutics to treat angiogenesis in cancer. Knowledge of the governing parameters for vessel formation is critical to the intelligent design of materials made to foster blood vessel growth for tissue-engineering applications and pharmaceuticals designed to intervene with newly formed vasculature in diseased tissue.","PeriodicalId":269533,"journal":{"name":"Advances in Regenerative Biology","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132555967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The word ‘significant’ is widely used in scientific papers. A PubMed search for ‘significant’ in June 2014 yielded more than two million results! But the word ‘significant’ has several meanings, and so is often misunderstood. There is a simple way to avoid this confusion: Avoid the word ‘significant’ and use alternative wording. (Published: 25 September 2014) Citation: Advances in Regenerative Biology 2014, 1 : 25155 - http://dx.doi.org/10.3402/arb.v1.25155
“显著”这个词在科学论文中被广泛使用。2014年6月，在PubMed上搜索“显著”，得到了超过200万个结果!但是“significant”这个词有好几层意思，所以经常被误解。有一个简单的方法可以避免这种混淆:避免使用“显著”这个词，使用替代的措辞。(发表于2014年9月25日)引文:Advances in Regenerative Biology 2014, 1: 25155 - http://dx.doi.org/10.3402/arb.v1.25155
{"title":"Opinion: Never use the word ‘significant’ in a scientific paper","authors":"H. Motulsky","doi":"10.3402/arb.v1.25155","DOIUrl":"https://doi.org/10.3402/arb.v1.25155","url":null,"abstract":"The word ‘significant’ is widely used in scientific papers. A PubMed search for ‘significant’ in June 2014 yielded more than two million results! But the word ‘significant’ has several meanings, and so is often misunderstood. There is a simple way to avoid this confusion: Avoid the word ‘significant’ and use alternative wording. (Published: 25 September 2014) Citation: Advances in Regenerative Biology 2014, 1 : 25155 - http://dx.doi.org/10.3402/arb.v1.25155","PeriodicalId":269533,"journal":{"name":"Advances in Regenerative Biology","volume":"44 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131811281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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