Andrew T. Metters

In situ forming degradable networks and their application in tissue engineering and drug delivery

Multifunctional macromers based on poly(ethylene glycol) and poly(vinyl alcohol) were photopolymerized to form degradable hydrogel networks. The degradation behavior of the highly swollen gels was characterized by monitoring changes in their mass loss, degree of swelling, and compressive modulus. Experimental results show that the modulus decreases exponentially with time, while the volumetric swelling ratio increases exponentially. A degradation mechanism assuming pseudo first-order hydrolysis kinetics and accounting for the structure of the crosslinked networks successfully predicted the experimentally observed trends in these properties with degradation. Once verified, the proposed degradation mechanism was extended to correlate network degradation kinetics, and subsequent changes in network structure, with release behavior of bioactive molecules from these dynamic systems. A theoretical model utilizing a statistical approach to predict the cleavage of crosslinks within the network was used to predict the complex erosion profiles produced by these hydrogels. Finally, the application of these macromers as in situ forming hydrogel constructs for cartilage tissue engineering is demonstrated.

Fundamental studies of a novel, biodegradable PEG-b-PLA hydrogel

The degradation behavior of highly swollen, chemically cross-linked hydrogels was characterized by monitoring changes in their mass loss, degree of swelling and compressive modulus. The hydrogels were used as model systems to investigate the hydrolytic degradation process in cross-linked networks. The trends of the three measured properties differ substantially from those seen for linear degradable systems; however, they can still be predicted accurately using hydrolysis kinetics and network structure. Experimental results show that the modulus decreases exponentially with time while the volumetric swelling ratios for these gels increase exponentially. The characteristic exponential time constants for these two functions, as well as the overall degradation timescale, are influenced greatly by the network structure. Thermodynamic relationships are used to explain these trends as well as relating the observed tradeoff between the two desirable properties of mechanical strength and water content.

Modeling release from degradable PEG hydrogels and their application in the delivery of osteoinductive growth factors

Multifunctional macromers based on poly(ethylene glycol) were photopolymerized to form degradable hydrogel networks. The degradation behavior of the highly swollen gels was characterized by monitoring changes in their degree of swelling and compressive modulus. Experimental results show that the modulus decreases exponentially with time, while the volumetric swelling ratio increases exponentially. A degradation mechanism assuming pseudo first-order hydrolysis kinetics and accounting for the structure of the crosslinked networks successfully predicted the experimentally observed trends in these properties with degradation. Once verified, the proposed degradation mechanism was extended to correlate network degradation kinetics, and subsequent changes in network structure, with release behavior of bioactive molecules from these dynamic systems. Finally, the application of these macromers as in situ forming hydrogel constructs for the delivery of osteoinductive growth factors and the production of mineralized tissue was demonstrated in vivo.

Optimization of synthetic hydrogel biomaterials through control of microstructure

The degradation behavior of highly swollen, chemically crosslinked hydrogels was characterized by monitoring changes in their mass loss, degree of swelling, and compressive modulus. The hydrogels were used as model systems to investigate the hydrolytic degradation process in crosslinked networks. The trends of the three measured properties differ substantially from those seen for linear degradable systems but can still be accurately predicted using hydrolysis kinetics and network structure. Experimental results verify theoretical predictions and show the modulus to decrease exponentially with time while the volumetric swelling ratios for these gels increase exponentially. The characteristic time constants for these two functions, as well as the overall degradation time-scale, are influenced greatly by the network structure. Thermodynamic relationships are used to explain these trends as well as to relate the observed tradeoff between the two desirable properties of mechanical strength and water content.