novel biodegradable materials

The objective of this work is to develop a novel degradable polymer which will form benign by-products upon degradation.  Hydrolytically degradable polymers are widely employed in biomedical applications, utilized both in the clinical setting as the major constituent of resorbable sutures and in the research setting as an artificial scaffold in many tissue engineering strategies.  Most degradable polymers studied, however, utilize either an ester or an amide group for hydrolytic degradation.  Upon degradation, esters form acids and alcohols, while amides form acids and amines. Unfortunately, the acidic degradation products that result from both esters and amides have been associated with adverse tissue responses, including an enhanced inflammatory response, a prolonged inflammatory response, and fibrous encapsulation. Therefore, we propose the development of the hydrolytically degradable biomaterials based upon a cyclic acetal unit.  The results of this project will initiate research into the development of a novel class of hydrolytically degradable polymers that are well suited for biomedical applications.

cell signaling in synthetic biomaterials

The objective of this work is to investigate molecular signal expression and transport within synthetic tissues.  Soluble signaling molecules, which include growth factors and cytokines, are significant effectors of cellular functions, directing cell proliferation, quiescence, differentiation, and death.  Nevertheless, while the role of signaling molecules has been vigorously examined in normal and pathogenic tissue, there remains a paucity of knowledge concerning their role in synthetic tissues.  Currently, the fabrication of synthetic tissues has focused upon the viability of cell populations within artificial matrices as well as the augmentation of matrix encapsulated cell function by the delivery of exogenous signaling molecules.  This work plans to build upon these well explored strategies by investigating the following novel concept: cell encapsulation within synthetic scaffolds alters the expression and transport of endogenous signaling molecules, therefore affecting cell function.  Therefore, we seek to develop a fundamental relationship between the properties of synthetic matrices and cell encapsulated signal expression and transport.

articular cartilage engineering

Acute skeletal injuries, chronic osteoarthritic diseases, and an aging population have allowed articular cartilage defects to be one of the most prevalent conditions in the United States.  In fact, over 17% of disabled persons in the United States suffer from arthritis.  The goal of this proposal is to treat articular cartilage defects by cartilage tissue regeneration.  The proposed strategy for articular cartilage regeneration is based upon the implantation of an engineered cartilage graft composed of autologous chondrocytes encapsulated within a degradable hydrogel scaffold.  In order to develop a method for delivering phenotypically stable chondrocytes to articular cartilage defects, we have initiated preliminary studies that examine the effects of an artificial matrix on encapsulated cell function.  In particular, we are developing an engineered cartilage graft that facilitates insulin-like growth factor-1 expression and function among encapsulated chondrocytes.

craniofacial bone repair

Orbital floor injuries are a devastating form of craniofacial trauma.  Current clinical treatments, including the implantation of plastics or metals, are often inadequate as they may lead to a loss of function as well as poor aesthetics.  Our strategy for orbital floor regeneration is based upon the in vitro preculture of osteoprogenitor cells within a degradable hydrogel.  The proposed work investigates whether bone defects can be successfully treated by implanting an engineered bone graft that promotes osteoprogenitor cell differentiation by augmenting bone morphogenetic protein-2 expression, transport, and function.  The successful completion of this work will allow us to develop a novel strategy for the treatment of orbital bone defects.

abdominal hernia repair

Abdominal wall hernias represent one of the most common pathologic conditions that afflict humans.  Although the true incidence of abdominal wall herniation is not known, the National Center for Health Statistics estimates that approximately 5 million Americans alone have an abdominal wall hernia.  In order to address the clinical concern, our laboratory has developed a class of cyclic acetal biomaterials which have been designed to degrade by hydrolysis, but without the buildup of acidic degradation products associated with many resorbable synthetic polymers.  We propose to utilize these biomaterials in the recruitment, differentiation, and maturation of a myoblastic cell population during the repair of skeletal muscle in abdominal hernias.

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