Kenneth James

Structure–property correlations in a combinatorial library of degradable biomaterials

A combinatorial library of degradable polyarylates was prepared. These polymers are A-B-type copolymers consisting of an alternating sequence of a diphenol and a diacid. The library was prepared by copolymerizing, in all possible combinations, 14 different tyrosine-derived diphenols and eight different aliphatic diacids, resulting in 8 x 14 = 112 distinct polymers. This approach (a) increases the number of available polymeric candidate materials for medical applications, and (b) facilitates the identification of correlations between polymer structure and glass transition temperature, air-water contact angle, mechanical properties, and fibroblast proliferation. The pendent chain and backbone structures were systematically varied by (a) simple homologative variations in the number of methylene groups, (b) substitution of oxygen for methylene groups, and (c) introduction of branched and aromatic structures. The polymers contained within the library exhibited incremental variations in Tg (from 2 degrees C to 91 degrees C) and air-water contact angle (from 64 degrees to 101 degrees ). Fibroblast proliferation (in vitro, serum-containing media) ranged from approximating that measured on tissue culture polystyrene to complete absence of proliferation. Generally, decreased proliferation correlated linearly with increased surface hydrophobicity, except in those polymers derived from oxygen-containing diacids in their backbone which were uniformly good growth substrates even if their surfaces were very hydrophobic. In a selected subgroup of polymers, tensile strength of thin solvent cast films ranged from about 6 to 45 MPa, while Youngs modulus (stiffness) ranged from about 0.3 to 1.7 GPa. Combinatorial biomaterial libraries such as these tyrosine-derived polyarylates permit the systematic study of material-dependent biological responses and provide the medical device designer with the option to choose a suitable material from a library of related polymers that encompasses a broad range of properties.

Canine bone response to tyrosine‐derived polycarbonates and poly(L‐lactic acid)

Tyrosine-derived polycarbonates are a new class of degradable polymers developed for orthopedic applications. In this study the long-term (48 week) in vivo degradation kinetics and host bone response to poly(DTE carbonate) and poly(DTH carbonate) were investigated using a canine bone chamber model. Poly(L-lactic acid) (PLA) served as a control material. Two chambers of each test material were retrieved at 6-, 12-, 24-, and 48-week time points. Tyrosine-derived polycarbonates were found to exhibit degradation kinetics comparable to PLA. Each test material lost approximately 50% of its initial molecular weight (Mw) over the 48-week test period. Poly(DTE carbonate) and poly(DTH carbonate) test chambers were characterized by sustained bone ingrowth throughout the 48 weeks. In contrast, bone ingrowth into the PLA chambers peaked at 24 weeks and dropped by half at the 48-week time point. A fibrous tissue layer was found surrounding the PLA implants at all time points. This fibrous tissue layer was notably absent at the interface between bone and the tyrosine-derived polycarbonates. Histologic sections revealed intimate contact between bone and tyrosine-derived polycarbonates. From a degradation-biocompatibility perspective, the tyrosine-derived polycarbonates appear to be comparable, if not superior, to PLA in this canine bone chamber model.

Small changes in polymer chemistry have a large effect on the bone–implant interface:: evaluation of a series of degradable tyrosine-derived polycarbonates in bone defects

In a series of homologous, tyrosine-based polycarbonates, small changes in the chemical structure of the polymer pendent chain were found to affect the bone response in a long-term (1280 d) implantation study. Identically sized pins, prepared from poly(DTE carbonate), poly(DTB carbonate), poly(DTH carbonate), and poly(DTO carbonate) were implanted transcortically in the proximal tibia and the distal femur of skeletally mature New Zealand White Rabbits. The tissue response at the bone-implant interface was characterized in terms of the absence of a fibrous capsule (direct bone apposition, indicative of a bone bonding response) or the presence of a fibrous capsule (referred to as the encapsulation response). The relative frequency of direct bone apposition versus encapsulation was recorded for each polymer throughout the entire period of the study. While all four polymers were tissue compatible, there was a correlation between the chemical structure of the pendent chain and the type of bone response observed, with poly(DTE carbonate) having the highest tendency to elicit direct bone apposition. Based on in vivo degradation data and the ability of model polymers with carboxylate groups at their surface to chelate calcium ions, it is proposed that the ability of poly(DTE carbonate) to bond to bone is caused by the facile hydrolysis of the pendent ethyl ester groups which creates calcium ion chelation sites on the polymer surface. The incorporation of calcium chelation sites into the chemical structure of an implant material appears to be a key requirement if direct bone apposition/bone bonding is desired. This study demonstrates that very subtle changes in the chemical composition of an implant material can have significant effects on the long-term tissue response in a clinically relevant model.

Small Animal Surgical and Histological Procedures for Characterizing the Performance of Tissue-Engineered Bone Grafts

Developing effective tissue-engineered constructs for bone regeneration requires careful assessment of the in vivo bone response to novel biomaterials, scaffold architectures, and biologically augmented, tissue-engineered constructs. Both the implant material and scaffold architecture are known to significantly effect the local tissue response (1-3). Consequently, in characterizing the performance of new bone implants, it is prudent to establish material-dependent and scaffold-architecture-dependent bone-growth phenomena, in addition to the effect of biological augmentation, e.g., preseeded cells, growth factors, and cell-attachment proteins. Here we describe rabbit transcortical pin and trephine defect models, which, in combination, yield a method to investigate such variables on bone regeneration. The necessary histological and histomorphometry procedures are also detailed.