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Papers by Nada Haq-Siddiqi

Advanced Drug Delivery Reviews

Low back pain is the most common cause of disability in the world and is often caused by degenera... more Low back pain is the most common cause of disability in the world and is often caused by degeneration or injury of the intervertebral disc (IVD). The IVD is a complex, fibrocartilaginous tissue that allows for the wide range of spinal mobility. Disc degeneration is a progressive condition believed to begin in the central, gelatinous nucleus pulposus (NP) region of the tissue, for which there are few preventative therapies. Current therapeutic strategies include pain management and exercise, or surgical intervention such as spinal fusion, none of which address the underlying cause of degeneration. With an increasingly aging population, the socioeconomic impact of disability associated with low back pain and disc degeneration cannot be understated. Tissue engineering strategies are increasingly being investigated as an alternative therapy by which early-stage degeneration may be halted and reversed, thus restoring disc mechanics and inducing biological repair to prevent more painful l...

Biomaterials, 2009

Poly(ethylene glycol) diacrylate (PEGDA) hydrogel scaffolds were engineered to promote contractil... more Poly(ethylene glycol) diacrylate (PEGDA) hydrogel scaffolds were engineered to promote contractile smooth muscle cell (SMC) phenotype via controlled release of heparin. The scaffold design was evaluated by quantifying the effects of free heparin on SMC phenotype, engineering hydrogels to provide controlled release of heparin, and synthesizing cell-adhesive, heparin releasing hydrogels to promote contractile SMC phenotype. Heparin inhibited SMC proliferation and upregulated expression of contractile SMC phenotype markers, including smooth muscle alpha actin, calponin, and SM-22 alpha, in a dose-dependent fashion (6 ug/ml-3.2 mg/ml). Heparin release from PEGDA hydrogels was controlled by altering PEGDA molecular weight (MW 1000-6000) and concentration at polymerization (10-30% w/w), yielding release profiles ranging from hours to weeks in duration. Heparin released from PEGDA gels, formulated for optimized heparin loading and release kinetics (30% w/w PEGDA, MW 3000), stimulated SMCs to up-regulate contractile marker mRNA. A cell-instructive scaffold construct was prepared by polymerizing a thin hydrogel film, with pendent RGD peptides for cell attachment, over the optimized hydrogel depots. SMCs seeded on these constructs had elevated levels of contractile marker mRNA after 3 d of culture compared with SMCs on control constructs. These results indicate that RGD-modified, heparin releasing PEGDA gels can act as cell-instructive scaffolds that promote contractile SMC phenotype. 1. Introduction Anastomotic intimal hyperplasia (IH) is a significant cause of long-term failure in synthetic vascular grafts. In this pathology, normal smooth muscle cells (SMCs), which exhibit a quiescent, contractile phenotype, de-differentiate into a phenotype characterized by proliferation and excessive synthesis of extracellular matrix (ECM) [1]. These "synthetic" SMCs are implicated in the stenosis of the vascular reconstruction and ultimately contribute to failure. Many stimuli induce this pathology, including mechanical mismatch, flow disturbances, and injury [1,2]. Vascular tissue engineering has the potential to mitigate the response to these stimuli by employing cells and tissues to provide the complex set of responses necessary to maintain long-term patency [3]. Scaffold materials designed to regulate SMC phenotype are an approach to realize this potential.

Advanced Drug Delivery Reviews

Low back pain is the most common cause of disability in the world and is often caused by degenera... more Low back pain is the most common cause of disability in the world and is often caused by degeneration or injury of the intervertebral disc (IVD). The IVD is a complex, fibrocartilaginous tissue that allows for the wide range of spinal mobility. Disc degeneration is a progressive condition believed to begin in the central, gelatinous nucleus pulposus (NP) region of the tissue, for which there are few preventative therapies. Current therapeutic strategies include pain management and exercise, or surgical intervention such as spinal fusion, none of which address the underlying cause of degeneration. With an increasingly aging population, the socioeconomic impact of disability associated with low back pain and disc degeneration cannot be understated. Tissue engineering strategies are increasingly being investigated as an alternative therapy by which early-stage degeneration may be halted and reversed, thus restoring disc mechanics and inducing biological repair to prevent more painful l...

Biomaterials, 2009

Poly(ethylene glycol) diacrylate (PEGDA) hydrogel scaffolds were engineered to promote contractil... more Poly(ethylene glycol) diacrylate (PEGDA) hydrogel scaffolds were engineered to promote contractile smooth muscle cell (SMC) phenotype via controlled release of heparin. The scaffold design was evaluated by quantifying the effects of free heparin on SMC phenotype, engineering hydrogels to provide controlled release of heparin, and synthesizing cell-adhesive, heparin releasing hydrogels to promote contractile SMC phenotype. Heparin inhibited SMC proliferation and upregulated expression of contractile SMC phenotype markers, including smooth muscle alpha actin, calponin, and SM-22 alpha, in a dose-dependent fashion (6 ug/ml-3.2 mg/ml). Heparin release from PEGDA hydrogels was controlled by altering PEGDA molecular weight (MW 1000-6000) and concentration at polymerization (10-30% w/w), yielding release profiles ranging from hours to weeks in duration. Heparin released from PEGDA gels, formulated for optimized heparin loading and release kinetics (30% w/w PEGDA, MW 3000), stimulated SMCs to up-regulate contractile marker mRNA. A cell-instructive scaffold construct was prepared by polymerizing a thin hydrogel film, with pendent RGD peptides for cell attachment, over the optimized hydrogel depots. SMCs seeded on these constructs had elevated levels of contractile marker mRNA after 3 d of culture compared with SMCs on control constructs. These results indicate that RGD-modified, heparin releasing PEGDA gels can act as cell-instructive scaffolds that promote contractile SMC phenotype. 1. Introduction Anastomotic intimal hyperplasia (IH) is a significant cause of long-term failure in synthetic vascular grafts. In this pathology, normal smooth muscle cells (SMCs), which exhibit a quiescent, contractile phenotype, de-differentiate into a phenotype characterized by proliferation and excessive synthesis of extracellular matrix (ECM) [1]. These "synthetic" SMCs are implicated in the stenosis of the vascular reconstruction and ultimately contribute to failure. Many stimuli induce this pathology, including mechanical mismatch, flow disturbances, and injury [1,2]. Vascular tissue engineering has the potential to mitigate the response to these stimuli by employing cells and tissues to provide the complex set of responses necessary to maintain long-term patency [3]. Scaffold materials designed to regulate SMC phenotype are an approach to realize this potential.