Orthomimetics

Orthomimetics

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Lynn A.K.,University of Cambridge | Lynn A.K.,Orthomimetics | Best S.M.,University of Cambridge | Cameron R.E.,University of Cambridge | And 4 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2010

This is the first in a series of articles that describe the design and development of a family of osteochondral scaffolds based on collagen- glycosaminoglycan (collagen-GAG) and calcium phosphate technologies, engineered for the regenerative repair of defects in articular cartilage. The osteochondral scaffolds consist of two layers: a mineralized type I collagen-GAG scaffold designed to regenerate the underlying subchondral bone and a nonmineralized type II collagen-GAG scaffold designed to regenerate cartilage. The subsequent articles in this series describe the fabrication and properties of a mineralized scaffold as well as a two-layer (one mineralized, the other not) osteochondral scaffold for regeneration of the underlying bone and cartilage, respectively. This article describes a technology through which the chemical composition - particularly the calcium phosphate mass fraction - of triple coprecipitated nanocomposites of collagen, glycosaminoglycan, and calcium phosphate can be accurately and reproducibly varied without the need for titrants or other additives. Here, we describe how the mineral:organic ratio can be altered over a range that includes that for articular cartilage (0 wt % mineral) and for bone (75 wt % mineral). This technology achieves the objective of mimicking the composition of two main tissue types found in articular joints, with particular emphasis on the osseous compartment of an osteochondral scaffold. Exclusion of titrants avoids the formation of potentially harmful contaminant phases during freeze-drying steps crucial for scaffold fabrication, ensuring that the potential for binding growth factors and drugs is maintained. © 2009 Wiley Periodicals, Inc.


Harley B.A.,University of Illinois at Urbana - Champaign | Lynn A.K.,Orthomimetics | Wissner-Gross Z.,Massachusetts Institute of Technology | Bonfield W.,University of Cambridge | And 2 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2010

This paper is the second in a series of papers describing the design and development of an osteochondral scaffold using collagen-glycosaminoglycan and calcium phosphate technologies engineered for the regenerative repair of articular cartilage defects. The previous paper described a technology (concurrent mapping) for systematic variation and control of the chemical composition of triple coprecipitated collagen, glycosaminoglycan, and calcium phosphate (CGCaP) nanocomposites without using titrants. This paper describes (1) fabricating porous, three-dimensional scaffolds from the CGCaP suspensions, (2) characterizing the microstructure and mechanical properties of such scaffolds, and (3) modifying the calcium phosphate mineral phase. The methods build on the previously demonstrated ability to vary the composition of a CGCaP suspension (calcium phosphate mass fraction between 0 and 80 wt %) and enable the production of scaffolds whose pore architecture (mean pore size: 50-1000 μm), CaP phase chemistry (brushite, octacalcium phosphate, apatite) and crosslinking density (therefore mechanical properties and degradation rate) can be independently controlled. The scaffolds described in this paper combine the desirable biochemical properties and pore architecture of porous collagen-glycosaminoglycan scaffolds with the strength and direct bone-bonding properties of calcium phosphate biomaterials in a manner that can be tailored to meet the demands of a range of applications in orthopedics and regenerative medicine. © 2009 Wiley Periodicals, Inc.


Harley B.A.,University of Illinois at Urbana - Champaign | Lynn A.K.,University of Cambridge | Lynn A.K.,Orthomimetics | Wissner-Gross Z.,Massachusetts Institute of Technology | And 3 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2010

There is a need to improve current treatments for articular cartilage injuries. This article is the third in a series describing the design and development of an osteochondral scaffold based on collagen-glycosaminoglycan and calcium phosphate technologies for regenerative repair of articular cartilage defects. The previous articles in this series described methods for producing porous, threedimensional mineralized collagen-GAG (CGCaP) scaffolds whose composition can be reproducibly varied to mimic the composition of subchondral bone, and pore microstructure and mineral phase can be modified. This article describes a method, "liquid-phase cosynthesis," that enables the production of porous, layered scaffolds that mimic the composition and structure of articular cartilage on one side, subchondral bone on the other side, and the continuous, gradual or "soft" interface between these tissues: the tidemark of articular joints. This design enables the layered scaffolds to be inserted into the subchondral bone at an osteochondral defect site without the need for sutures, glue, or screws, with a highly interconnected porous network throughout the entire osteochondral defect. Moreover, the differential moduli of the osseous and cartilaginous compartments enable these layered scaffolds to exhibit compressive deformation behavior that mimics the behavior observed in natural articular joints. © 2009 Wiley Periodicals, Inc.


Enea D.,University of Cambridge | Enea D.,Marche Polytechnic University | Henson F.,University of Cambridge | Kew S.,Orthomimetics | And 4 more authors.
Journal of Materials Science: Materials in Medicine | Year: 2011

Reconstituted collagen fibres are promising candidates for tendon and ligament tissue regeneration. The crosslinking procedure determines the fibres' mechanical properties, degradation rate, and cell-fibre interactions. We aimed to compare mechanical and biological properties of collagen fibres resulting from two different types of crosslinking chemistry based on 1-ethyl-3-(3- dimethyllaminopropyl)carbodiimide (EDC). Fibres were crosslinked with either EDC or with EDC and ethylene-glycol-diglycidylether (EDC/EGDE). Single fibres were mechanically tested to failure and bundles of fibres were seeded with tendon fibroblasts (TFs) and cell attachment and proliferation were determined over 14 days in culture. Collagen type I and tenascin-C production were assessed by immunohistochemistry and dot-blotting. EDC chemistry resulted in fibres with average mechanical properties but the highest cell proliferation rate and matrix protein production. EDC/EGDE chemistry resulted in fibres with improved mechanical properties but with a lower biocompatibility profile. Both chemistries may provide useful structures for scaffolding regeneration of tendon and ligament tissue and will be evaluated for in vivo tendon regeneration in future experiments. © Springer Science+Business Media, LLC 2011.


Mullen L.M.,University of Cambridge | Best S.M.,University of Cambridge | Brooks R.A.,University of Cambridge | Ghose S.,Orthomimetics | And 4 more authors.
Tissue Engineering - Part C: Methods | Year: 2010

Tissue engineering is a promising technique for cartilage repair, but to optimize novel scaffolds before clinical trials, it is necessary to determine their characteristics for binding and release of growth factors. Toward this goal, a novel, porous collagen-glycosaminoglycan scaffold was loaded with a range of concentrations of insulin-like growth factor-1 (IGF-1) to evaluate its potential as a controlled delivery device. The kinetics of IGF-1 adsorption and release from the scaffold was demonstrated using radiolabeled IGF-1. Adsorption was rapid, and was approximately proportional to the loading concentration. Ionic bonding contributed to this interaction. IGF-1 release was studied over 14 days to compare the release profiles from different loading groups. Two distinct phases occurred: first, a burst release of up to 44% was noted within the first 24h; then, a slow, sustained release (13%-16%) was observed from day 1 to 14. When the burst release was subtracted, the relative percentage of remaining IGF-1 released was similar for all loading groups and broadly followed t1/2 kinetics until approximately day 6. Scaffold cross-linking using dehydrothermal treatment did not affect IGF-1 adsorption or release. Bioactivity of released IGF-1 was confirmed by seeding scaffolds (preadsorbed with unlabeled IGF-1) with human osteoarthritic chondrocytes and demonstrating increased proteoglycan production in vitro. © Copyright 2010, Mary Ann Liebert, Inc.


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