Journal of Biomedical Materials Research Part B: Applied Biomaterials

Cover image for Vol. 104 Issue 4

Edited By: Jeremy L. Gilbert

Impact Factor: 2.759

ISI Journal Citation Reports © Ranking: 2014: 18/33 (Materials Science Biomaterials); 22/76 (Engineering Biomedical)

Online ISSN: 1552-4981

Associated Title(s): Journal of Biomedical Materials Research Part A

Virtual Issues

Progress in Biomaterials: Celebrating the 100th Volume of the Journal of Biomedical Materials Research

JBM Virtual Issue


Edited by: James M. Anderson and Jeremy L. Glilbert

Click here to read an introduction from the Editors

Tissue Adhesives and Hemostasis-Inducing Compounds: The Alkyl Cyanoacrylates

F. Leonard, R.K. Kulkarni, J. Nelson, and G. Brandes

1967; 1:3-9


This pioneering contribution by Fred Leonard and colleagues was the first manuscript published in the Journal of Biomedical Materials Research. After a 30-40 year hiatus, these materials have finally achieved clinical application. These materials were utilized by the Army Medical Corps in Vietnam to treat acute trauma. Perhaps one of the reasons for not achieving widespread clinical use is related to the in vivo biocompatibility studies. Anecdotally, as told to James M. Anderson by Fred Leonard, there was an attempt to determine in vivo biocompatibility by implanting these materials that had been prepared using radiolabelled monomers. In attempting to determine the histological characteristics, the findings demonstrated adverse tissue responses, which were later attributed to the effect of radiation as opposed to biodegradation, which was a useful characteristic of these materials. This wrong interpretation of the findings due to the dual use manner of determining biocompatibility and biodegradation is a lesson to biomaterials scientists attempting to minimize the use of animals in in vivo studies and subsequently suggests caution and the proper selection of tests to simultaneously determine biodegradation and biocompatibility.


Identification of Rapid Changes at Plasma-Solid Interfaces

L. Vroman and A.L. Adams

1969; 3(1):43-67


Initial Events in Interactions of Blood with a Foreign Surface

R.E. Baier and B.C. Dutton

1969; 3(1):191-206


Leo Vroman and Ann Adams (Vroman effect) and Bob Baier and Bob Dutton (protein preconditioning hypothesis) have made seminal contributions to our initial conceptions of blood- material interactions. These articles focused attention to specific proteins, immunoglobulins, and fibrinogen, respectively, promoting investigations by many scientists that have underscored the importance and deepened the understanding of the nature of biological tissue interactions with foreign surfaces. Leo Vroman, a true Renaissance man, continues to publish poetry volumes and cartoons in his 93rd year.


Potential of Ceramic Materials as Permanently Implantable Skeletal Prostheses

S.F. Hulbert, F.A. Young, R.S. Mathews, J.J. Klawitter, C.D. Talbert and F.H. Stelling

1970; 4:433-456


Sam Hulbert and colleagues pioneered the concept of porous materials for the permanent repair of skeletal defects and as a method to permanently attach implants to the living skeletal system. Porosity is still a key materials property in developing tissue-engineered materials for a wide variety of applications. It is noteworthy that every orthopaedic device manufacturer today has some form porous calcium phosphate devices.


Bonding Mechanisms at the Interface of Ceramic Prosthetic Materials

L.L. Hench, R.J. Splinter, T.K. Greenlee and W.C. Allen

1971; 2(1):117-141


This work by Larry Hench and colleagues clearly changed the paradigm of biomaterials to providing the perspective of “bioactive” surfaces and that a bioactive ceramic could facilitate tissue attachment.


The Effect of Movement on the Bonding of Porous Metal to Bone

H.U. Cameron, R. M. Pilliar, I. Macnab

1973; 7(4),  301–311


While early papers by Hench and Hulbert (cited above) were seminal in introducing the concept of porous surfaces for biological fixation, this work was one of the first to assess what role mechanical factors at the tissue-biomaterial interface played in biological fixation.  The finding that biological fixation is dependent on the motion of the interface relative to the porosity of the surface was seminal and led to a wide range of follow-on studies looking at micromotion, porosity and fixation.


Mechanical Properties of Bone Cements Containing Large Doses of Antibiotic Powders

E. P. Lautenschlager, J. J. Jacobs, G. W. Marshall, P. R. Meyer Jr.




This work provided insight into the effects of antibiotic loading in orthopedic bone cement, which is a major mean, even today, to treat infected orthopedic sites.Overall, the work by Lautenschlager on bone cement performance and structure property relationships was instrumental in developing cements and mixing systems that are still in use today.


Reactions of Articular Capsule to Wear Products of Artificial Joint Prostheses

H.G. Willert and M. Semlitsch

1977; 11(2):157-164


This 1977 paper by Willert and Semlitsch was truly visionary when one considers today’s unrelenting focus on the inflammatory response to wear particulates produced in artificial joint devices. This work clearly identified the importance of implant retrieval and evaluation and the identification of failure mechanisms by artificial joint prostheses.


Effect of Implant Surface Chemistry upon Arterial Thrombosis

C.L. Van Kampen, D.F. Gibbons, and R.D. Jones

1979; 13:517-541


This in vivo study by Van Kampen, Gibbons, and Jones utilized hydrophobic, hydrophilic, ionic, and nonionic materials to investigate the effect of surface chemistry on thrombosis and vessel occlusion for time periods out to two weeks implantation in canine femoral and carotid arteries. The major difference between materials that progressed to thrombosis and rapid vessel occlusion (hydrophobic) and materials that remained patent (hydrophilic and ionic) was the degree of direct leukocyte adherence and spreading on the implant surface prior to extensive platelet aggregation. When thrombosis was non-occlusive, the surfaces became endothelialized. A hypothetic model representing the sequence of events and alternative pathways occurring at the blood-material interface, with special mention to the involvement of leukocytes in arterial thrombosis, was presented.


Design of an Artificial Skin. I. Basic Design Principles

I.V. Yannas and J.F. Burke

1980; 14(1):65-81


This design of an artificial skin and a collagen scaffold has become the first tissue-engineered product to be approved by the FDA (1996). It is currently used with the trademark Integra™. It has found exceptional clinical application in the treatment of burns, reconstructive surgery, and chronic skin wounds.


Friction and Wear Properties of Polymer, Metal, and Ceramic Prosthetic Joint Materials Evaluated on a Multi-Channel Screening Device

H.A. McKellop, I.C. Clarke, K.L. Markolf and H.A. Amstutz

1981; 15:619-653


Harry McKellop and colleagues developed a 12-station pin-on-disc apparatus that helped to establish the credibility and usefulness of pre-clinical laboratory wear simulations, and contributed to the subsequent development of reliable hip and knee joint simulators. These, in turn, provided the tools that made possible the development of improved bearing materials, such as highly crosslinked polyethylene, and identified the poor wear properties of several bearing materials that were already in clinical use at the time, i.e., polyacetal.


Blood-Material Interactions – The Minimum Interfacial Free-Energy and the Optimum Polar /Apolar Ratio Hypotheses

D.L. Coleman, D.E. Gregonis, J.D. Andrade

1982; 16:381-398


This work tested two hypotheses that had been put forth to explain observed blood-materials interactions. Methacrylate polymers and copolymers were characterized by numerous surface characterization techniques and in vitro blood tests including various clotting times and platelet adhesion. The results indicated the need for a multi-parameter approach to blood-materials testing and that platelet adhesion can be a misleading indicator of blood compatibility. Neither hypothesis explained the apparent conflict between the platelet adhesion data and the coagulation time data.


Protein-Resistant Surfaces Prepared by PEO-Containing Block Copolymer Surfactants

J.H. Lee, J. Kopecek and J.D. Andrade

1989; 23(3):351-368


Lee, Kopecek, and Andrade studied protein adsorption on surfaces modified by polyethylene oxide (PEO)-containing nonionic polymeric surfactants. The protein resistance of the surfactant-treated surfaces was clearly demonstrated and provided the basis for subsequent studies utilizing PEO-containing polymers for surface modification of blood-contacting biomedical polymers.


Cellular Interactions with Biomaterials: In vivo Cracking of Pre-Stressed Pellethane 2363-


Q. Zhao, M.P. Agger, M. Fitzpatrick, J.M. Anderson, A. Hiltner, K. Stokes and P. Urbanski

1990; 24:621-637


Zhao and colleagues demonstrated in this in vivo study the capability of macrophages to degrade the polyether soft segment of polyether polyurethanes. This work provided a mechanism for identifying the failure mechanism of polyether polyurethane coated pacemaker leads and led to further studies and development of polyurethanes in which the soft segment component was not susceptible to biodegradation. This work resulted in a paradigm shift in the pacemaker lead industry regarding lead insulation by polyurethanes.


Protein Adsorption from Human Plasma Is Reduced on Phospholipid Polymers

K. Ishihara, N.P. Ziats, B.P. Tierney, N. Nakabayashi and J.M. Anderson

1991; 25(11):1397-1407


Ishihara and colleagues demonstrated that the incorporation of poly (2-methacryloyloxyethyl phosphorylcholine (MPC)) into methacrylate copolymers and an increase in MPC composition resulted in a suppression of protein adsorption and therefore had the potential to reduce thrombus formation. MPC polymers and copolymers are commercially available for surface modification of blood-contacting surfaces in medical devices.


Protein Adsorption to Poly (Ethylene Oxide) Surfaces

W.R. Gombotz, W. Guanghui, T.A. Horbett and A.S. Hoffman

1991; 25(12):1547-1562


Gombotz and colleagues demonstrated that polyethylene terephthalate films grafted with low molecular weight polyethylene oxide (PEO) contained more PEO molecules than surfaces grafted with high molecular weight PEO. The high molecular weight PEO surfaces exhibited greater wettability (lower water contact angles) and decreased fibrinogen and albumin adsorption than the low molecular weight PEO surfaces. The authors hypothesized that the larger PEO molecules created cooperative water structuring around the larger PEO molecules leading to an enhanced excluded volume of the hydrated polymer coils that, in turn, contributed to the observed low protein adsorption.


Glow-Discharge Plasma Deposition of Tetraethylene Glycol Dimethyl Ether for Fouling-Resistant Biomaterial Surfaces

G.P. Lopez, B.D. Ratner, C.D. Tidwell, C.L. Haycox, R.J. Rapoza and T.A. Horbett

1992; 26(4):415-439


Lopez and colleagues utilized glow discharge plasma deposition to form fouling-resistant, PEO-like surfaces on numerous substrates. Reduction in blood protein adsorption, dynamic platelet adhesion, and endothelial cell attachment further demonstrated the short-term non-adhesiveness of these surfaces of the tetraethylene glycoldimethylether glow discharge plasma deposition.


A novel recovery system for cultured cells using plasma-treated polystyrene dishes grafted with poly (N-isopropylacrylamide)

T. Okano, N. Yamada, H. Sakai, and Y. Sakurai



This pioneering study established that poly (N-isopropylacrylamide) grafted to surfaces of cell culture polystyrene could function as thermal switches for reversing cell attachment and detachment without cell damage. The PIPAAm-grafted surfaces were hydrophilic below 32 degrees C and hydrophobic above 32 degrees C permitting cellular sheets to be developed and utilized clinically. Subsequent studies in humans clearly have demonstrated the potential for this technology in corneal replacement surgery as well as cardiac myocardial replacement following myocardial infarction.


In vivo Corrosion of Modular Hip Prosthesis Components in Mixed and Similar MetalCombinations: The Effect of Crevice, Stress, Motion and Alloy Coupling

J.L. Gilbert, C.A. Buckley, J.J. Jacobs

1993: 27(12); 1533-1544


This work was one of the earliest studies that systematically analyzed the nature of corrosion processes taking place within metal-metal connections of modular taper designs.  Given that corrosion of metal orthopedic devices, and in particular the modular taper connections that have come to be common in these devices, is one of the most significant biomaterials-related problems in medical devices today, this paper serves as an early indicator of the nature and type of problems related to corrosion.



Macrophage/Particle Interactions: Effect of Size, Composition and Surface Area

A.S. Shanbhag, J.J. Jacobs, J. Black, J.O. Galante and T.T. Glant

1994; 28:81-90


Shanbhag and colleagues utilized the concept of surface area ratio to study and compare macrophage responses to wear particles in a standardized manner. Titanium and polystyrene particles (<2 microns) were utilized in dosages based on the ratio of the surface area of the particles to the surface area of the cell. The effect of size and composition on the bone resorbing activity, fibroblast proliferation, and secretion of IL-1 and PEG2 were determined. The macrophage response to particulate debris appeared to be dependent on particle size, composition, and dose as given by the surface area ratio.


Detection of antibodies against corrosion products in patients after Co-Cr total joint replacements

J. Yang and K. Merritt

1994; 28:1249-1258


This study by Yang and Merritt presented evidence that metal-protein complex-specific antibodies can be detected in patients after implantation of F-75 cobalt alloy total joint replacements. Detection of humeral immunity, antibodies, to nickel, cobalt, and chromium protein conjugates established the foundation for detection of corrosion and wear products of metallic orthopaedic devices.


Bone formation by three-dimensional stromal osteoblast culture in biodegradable polymer scaffolds

S.L. Ishaug, G.M. Crane, M.J. Miller, A.W. Yasko, M.J. Yaszemski and A.G. Mikos

1997; 36(1):17-28


The significance of this contribution by Mikos and colleagues is in the demonstration of biodegradable 3-D scaffolds that facilitate the proliferation and differentiation of osteoblasts. This work set the stage for a significant amount of research that continues to the present, on the in vitro/ex vivo approaches to the tissue engineering of bone structures.


Incorporation of Adhesion Peptides into Nonadhesive Hydrogels Useful for Tissue Resurfacing

D.L. Hern and J.A. Hubbell

1998; 39(2):266-276


Hern and Hubbell showed that modification of polyethylene glycol (PEG) hydrogels could facilitate cell adhesion when modified by the incorporation of RGD (ARG-GLY-ASP)-containing peptide sequences. Incorporation of a spacer arm (PEG MW 3400) enhanced the cell attachment and spreading in a dose-dependent manner.


Electrospun Nanofibrous Structure: A Novel Scaffold for Tissue Engineering

W-J. Li, C.T. Laurencin, E.J. Caterson, R.S. Tuan and F.K. Ko

2002; 60:613-621


This pioneering paper by Laurencin showed that biodegradable electrospun nanofiber structures were capable of supporting cell attachment and proliferation and indicated that cells seeded on this structure could maintain phenotypic shape and guide growth according to nanofiber orientation.


Surface Chemistry Modulates Fibronectin Conformation and Directs Integrin Binding and Specificity to Control Cell Adhesion

B.G. Keselowsky, D.M. Collard and A.J. García

2003; 66(2):247-259


This work established the paradigm that cell response to material properties could be mediated by protein adsorption. The work provided a mechanism whereby material chemistry dictates adsorbed protein conformation which further dictates integrin ligation and cell function. A new strategy for biomaterials design where material chemistry should be optimized to drive adsorbed proteins into a conformation that facilitates the desired cell response is presented in this work. This work established an experimental framework to analyze adhesive mechanisms controlling cell-surface interactions and provided a general strategy for surface-directed control of adsorbed protein activity to manipulate cell function in biomaterial and biotechnology applications.