J. BIOMED. MATER. RES. SYMPOSIUM
NO.6, pp. 1-7 (1975)
Bone Growth into Porous Carbon, Polyethylene, and Polypropylene Prostheses HERMAN J . CESTERO, J R . and KENNETH E. SALYER, Division of Plastic Surgery, The University of Texas Southwestern Medical School, Dallas, and I. RICHARD TORANTO, The University of Texas Southwestern Medical School, Dallas, Texas 75235.
Summary Using rats as a model, porous discs of RPG carbon and polypropylene and polyethylene were localized subperiosteally and supraperiosteally in the skull. Bone and blood vessels grew into the discs, which had adequate pore size, when placed in direct contact with bone. No bone was generated from the periosteum. Both plastic materials were estimated to be better than carbon for use in osseous reconstructive work. More long term material-tissue stability and reaction studies should be performed.
INTRODUCTION Bone is a highly specialized connective tissue. Its specific biological, mechanical, and morphological characteristics change according to age, location, and function[l]. By combining an organic compound such as bone collagen with inorganic salts it achieves its unique characteristics. It is strong enough to carry large amounts of weight, but it is relatively light in weight and not brittle. It has enough elasticity to tolerate a certain amount of impact, but is rigid enough to resist deformation by torsion or high pressure beyond any other tissue. Normally bone exists in an active equilibrium between continuous reabsorption and deposition. It can remodel itself to meet new conditions and has a fantastic healing ability. Ideally, any material designed as a bone substitute should possess these characteristics. Bone is also one of the most richly vascularized tissues in the human body [2]: no osteocyte is more than 0.5 mm distant from a bIood vessel. This extensive vascularization is essential to bone. Devascularized bone dies. It cannot be sustained by plasmatic diffusion of oxygen and nutrients from adjacent tissues. An interest in ceramics as a substitute for bone began with Smith’s [3] use of Cerosium. His work has been supported and amplified by papers which demonstrate that different ceramic prostheses (as well as porous 1
0 1975 by John Wiley & Sons, Inc.
2
CESTERO, SALYER, AND TORANTO
polymers) are capable of inducing* bone growth into them. Pore size, as well as other physical and biochemical characterics of the material definitely influence the quantity and quality of bone growth [4]. The plastic and reconstructive surgeon needs a better understanding of bone formation and growth to accomplish a successful replacement after ablative head and neck surgery and for reconstruction in the rapidly growing and expanding field of orbito-cranio-facial surgery. The need for a bone substitute is obvious at the present time and the clinical potential shown by RPG porous carbon [ 5 ] , and porous polymeric materials [6] has motivated this study.
MATERIALS AND METHODS Adult Sprague-Dawley male rats, weighing 250 to 300 g, were utilized for this study. Discs of various materials with different pore size (Tables I and 11) measuring 8 mm in diam by 2 to 4 mm in thickness were inserted into the skull area of the periosteal region (Fig. 1). The animals were fed a diet of Purina Formulab Chow 5003. The discs were retrieved at the intervals described in Tables I and 11, and two animals were sacrificed at each interval-material-location. The animals were sacrificed with an injection of Nembutal and heparin. In selected cases, study of vascularization was carried out by perfusion with a suspension containing
Fig. 1. An incision is performed in the posterior auricular area and is carried down to a location above the periosteum, or below the periosteum. Then, by blunt dissection, a pocket is created and the test discs are inserted in a position (a) above or (b) below the periosteum. The borders of the incision are sutured together with 4-0silk.
* The word “inducing” has been used by the authors for lack of a better term to describe the process that is taking place. Actually, it is not known whether bone grows into the materials because of induction, or simply because it is allowed to grow in.
BONE GROWTH
3
TABLE I Supraperiosteally Implanted Discs 10 Weeks
RPG carbon- carbon 1.79 g/cc Pore size:+ 20micron
Loosely ~ t t a r h e d Thin capsule to soft tissues but around disc. not to bane.
Thicker ropsule. Some vessels in capsule, some barely entering the disc. Few extrusions?
RPG carbon-carbon
Loosely attached to roft tissues but not to bone.
Some attarhment to soft tissues.
Several extrusions. Some vessels penetrating the periphery. N o bone growth?
Loosely attached to soft tissues but not to bane.
Some attachment to soft tissues. Same disrs extruded
Many extrussians. Slightly better vessel penetration than above. N o bone growth.'
0.191 g/cc 70-80 ppia
15 Weeks
30 Weeks
Materials
~~
RPG carbon-carbon 0.096 g/cc
3-60 ppia Polypropylene Pore size: 300 micron
Good attachment Tightly attached to soft tissues but to soft tissues. No not to bone.a bone growth. One extrusion?
Polyethylene Pore size: 200 micron
Good attachment to soft tissues but not to bone.a
a
Tightly attached to soft tissues. N o
bone growth."
Denotes perfusion with radio-opaque material was performed.
TABLE I1 Subperiosteally Implanted Discs Abterials
10 Weeks
15 Weeks
30 Weeks
RPG carbon-rorbon 1.79 g/cc Pore Size: *20 mtron
No attachment to bone. No bone growth.
No attachment to bone. No bone growth.
Vessels seen i n periosteum. No bone growth into the discs."
RPG carbcn-carbon ppia
Loosely attached to bone. Some osteoid ot base.
Better attarhment Osteoid at base and into matrix.
Very good attachment to bone. Mature bone ond vessels growing into dire?
RPG carbon-carbon 0.05'6 g/cc 50-60 ppia
Attached to bone but can be seporated easily.
Good attachment Mature bone at base. Matrix full with asteoid.
Excellent attachment. Bone and vessels growing a l l the way into tlp material. One extrusion
Polypropylene Pare Size : 330 micron
Loosety attached to bone. Same vesselr penetrating:
Goad attachment to bane and vessel ingrowth .Osteoid at base and matrix.a
Polyethylene Pore Slze: 206 micron
Laasety attarhed Good uttachment to bone. Some ve- to bone and vessel rsels penetrating.a ingrowth. Osteoid at base and matrix.
0.191 g/cc
70-80
a
Denotes perfusion with radio-opaque material was performed.
.-
-
4
CESTERO, SALYER, AND T0RA”I’O
200 g of Micropaque and 50 g of gelatin dissolved in 1 1. water at a temperature of 38°C and at a constant pressure of 120 mm Hg. Diameterically oriented, 1 mm thick sections of each disc, together with a portion of skull, were obtained using a high speed carborundum disc. Microradiographs were performed on 2 x 2 Kodak projector slide plates in a Faxitron (Grentz Ray) unit. Correlating histologic sections for microscopic examination were prepared by the technique described by Klawitter [7] and stained with the polychromatic stain Paragon C1306.
RESULTS All the implanted materiai that was located above the periosteum failed to show bone growth. A vascularized capsule formed around the implants (Fig. 2 ) , and usually there was little vascular penetration into the prostheses. Several of the implants in this location were extruded, usually after 15 weeks. When the prosthesis was placed as an onlay graft under the periosteum, there was good bone and blood vessel growth into all of them from the point of contact with bone. The periosteum from above contributed some vessels but no bone (Figs. 2-4). The carbon prostheses with pore s i x less than 20 p (1.79 g/cc), failed to show bone growth as was expected. Bone growth into the material, usually was anteceded by the following order of events: first, there was vessel ingrowth (mostly from the bone side) accompanied by a rather acellular ground substance, that later was replaced by osteoid in the typical lamellar pattern and eventually became calcified into mature bone. The authors suspect that this acellular substance is unorganized bone collagen and therefore have called it preosteoid. At present, we are in the process of analyzing this substance. It was also observed that most of the carbon prostheses released microparticles which migrated through the lymphatics and stained the
Fig. 2. Microradiograms of polypropylene discs after perfusion (2.5 x). (a) 10 weeks old, above the periosteum; (b) 15 weeks old, above the periosteum; (c) 10 weeks old, below the periosteum; (d) 15 weeks old, below the periosteum.
BONE GROWTH
5
Fig. 3 . 2.5 x microradiograph of a 30 weeks porous carbon (0.191 gm/cc) disc located below the periosteum. New bone (NB) shows as “cotton balls” left side. Calvarial bone (Ca) is seen on the right side. Larger periosteal vessels are indicated (Pv). Upper right corner is microphotograph of small vessels that have penetrated into the discs. (100 x).
Fig. 4. 100 x Microphotograph of a 30 weeks porous carbon (0.096 gm/cc) disc located below the periosteum. New mature bone (NB) is seen growing into the carbon (Cb) interstice. Uncalcified osteoid (Od) i s indicated by arrow.
6
CESTERO, SALYER, AND TORANTO
subcutaneous tissues. In general, early bone growth was favored by a larger pore size, but by 30 weeks the difference was minimal. There was no significant difference in the quality or quantity of bone growth that could be attributed to material differences other than pore size. DISCUSSION Bone accompanied by blood vessels grows into porous carbon as well as into polyethylene and polypropylene when placed as onlay grafts if the pores are of adequate size. The material studied did not perform to our satisfaction in the soft tissues. There seems to be a future in reconstructive bone surgery for these materials, especially the plastic ones. The extreme brittleness of the carbon, as well as its tendency to release small particles that stain the tissues, makes the carbon less desirable even though design improvements could make it more suitable. Both porous polyethylene and polypropylene discs showed about the same osseous growth and vascular penetration qualities. I n addition, they are more elastic and resistant to impact. Their consistency allows cutting with a knife to mold them at the operating table, even though a preformed prosthesis from a preoperative mold cast from the defect seems preferable. Long term degradation by the physiological environment and tissue (bone) reaction studies as well as bonematerial stress resistance studies should be performed before they are freely used in clinical application. Another interesting observation is that in all prosthesis, bone failed to grow from either side of the periosteum, even though the same prostheses showed bone growth from the side that was in contact with bone. This is in disagreement with the general belief that periosteum generates bone. CONCLUSIONS Bone and blood vessels will grow into porous carbon and plastic prostheses placed as onlay grafts. Pore size is a very important factor. The carbon prostheses with larger pore sizes, 70 to 80 ppia and 50 to 60 ppia, gave satisfactory growth; the carbon prostheses with the smallest pore size, 20 p , did not. Polyethylene (pore size 200 p) and polypropylene (pore size 300 p) gave adequate results. Soft tissue fixation is unsatisfactory, especially for porous carbon, which showed a high tendency to extrusion. The plastic prostheses were not in place long enough to establish a soft tissue pattern, as most carbon extrusions came after 15 weeks. The periosteum failed to show bone generation capacity in this experiment. This study was supported by the Plastic Surgery Research Facility, Veteran’s Hospital, Dallas, Texas, and the Southern Medical Association.
BONE GROWTH
7
The authors wish to express their appreciation to Joan Kmetz for her valuable assistance in writing this paper. They are also indebted to Jerome J . Klawitter, Ph. D., for his contribution. The RPG porous carbon produced by Super-Temp, Inc., and the porous polyethylene and polypropylene produced by Porex, Inc., Fairburn, Georgia, were provided by Zimmer U.S.A., who also provided for the sectioning of the implanted material.
References [I] H. Yamada, in Strength of Biological Materials, F. G . Evans, ed., Williams & Wilkins Co., Baltimore, 1970. [2] T. S. Leeson and C . R. Leeson, Histology, W. B. Saunders Co., Philadelphia, 1970. [3] L. Smith, Arch. Surg. 87, 653 (1963). [4] S. F. Hulbert, “use of ceramics in surgical implants,” paper present at Biomaterials-The Case for Ceramics Symp. Clemson University, Clemson, South Carolina, 1969. [5] M. J. Lapitsky, Investigation of Bone Ingrowth in Porous Carbons, M . S. Thesis, University of Washington, Seattle, Wash. (1972). [ 6 ] B. W. Sauer, J. J. Klawitter, S. F. Hulbert, R. B . Leonard, and J. G. Bagwell, “The role of porous polymeric materials in prosthesis attachment,” paper the 5th Annu. Biomater. Symp. Clemson University, Clemson, South Carolina, 1972. [7] J. J . Klawitter, “Attachment of prostheses by bone growth into porous materials-techniques for microstructural evaluation,” paper presented at Amer. Acad. Orthopedic Surgeons, Las Vegas, Nevada, 1973.
NO.6, pp. 1-7 (1975)
Bone Growth into Porous Carbon, Polyethylene, and Polypropylene Prostheses HERMAN J . CESTERO, J R . and KENNETH E. SALYER, Division of Plastic Surgery, The University of Texas Southwestern Medical School, Dallas, and I. RICHARD TORANTO, The University of Texas Southwestern Medical School, Dallas, Texas 75235.
Summary Using rats as a model, porous discs of RPG carbon and polypropylene and polyethylene were localized subperiosteally and supraperiosteally in the skull. Bone and blood vessels grew into the discs, which had adequate pore size, when placed in direct contact with bone. No bone was generated from the periosteum. Both plastic materials were estimated to be better than carbon for use in osseous reconstructive work. More long term material-tissue stability and reaction studies should be performed.
INTRODUCTION Bone is a highly specialized connective tissue. Its specific biological, mechanical, and morphological characteristics change according to age, location, and function[l]. By combining an organic compound such as bone collagen with inorganic salts it achieves its unique characteristics. It is strong enough to carry large amounts of weight, but it is relatively light in weight and not brittle. It has enough elasticity to tolerate a certain amount of impact, but is rigid enough to resist deformation by torsion or high pressure beyond any other tissue. Normally bone exists in an active equilibrium between continuous reabsorption and deposition. It can remodel itself to meet new conditions and has a fantastic healing ability. Ideally, any material designed as a bone substitute should possess these characteristics. Bone is also one of the most richly vascularized tissues in the human body [2]: no osteocyte is more than 0.5 mm distant from a bIood vessel. This extensive vascularization is essential to bone. Devascularized bone dies. It cannot be sustained by plasmatic diffusion of oxygen and nutrients from adjacent tissues. An interest in ceramics as a substitute for bone began with Smith’s [3] use of Cerosium. His work has been supported and amplified by papers which demonstrate that different ceramic prostheses (as well as porous 1
0 1975 by John Wiley & Sons, Inc.
2
CESTERO, SALYER, AND TORANTO
polymers) are capable of inducing* bone growth into them. Pore size, as well as other physical and biochemical characterics of the material definitely influence the quantity and quality of bone growth [4]. The plastic and reconstructive surgeon needs a better understanding of bone formation and growth to accomplish a successful replacement after ablative head and neck surgery and for reconstruction in the rapidly growing and expanding field of orbito-cranio-facial surgery. The need for a bone substitute is obvious at the present time and the clinical potential shown by RPG porous carbon [ 5 ] , and porous polymeric materials [6] has motivated this study.
MATERIALS AND METHODS Adult Sprague-Dawley male rats, weighing 250 to 300 g, were utilized for this study. Discs of various materials with different pore size (Tables I and 11) measuring 8 mm in diam by 2 to 4 mm in thickness were inserted into the skull area of the periosteal region (Fig. 1). The animals were fed a diet of Purina Formulab Chow 5003. The discs were retrieved at the intervals described in Tables I and 11, and two animals were sacrificed at each interval-material-location. The animals were sacrificed with an injection of Nembutal and heparin. In selected cases, study of vascularization was carried out by perfusion with a suspension containing
Fig. 1. An incision is performed in the posterior auricular area and is carried down to a location above the periosteum, or below the periosteum. Then, by blunt dissection, a pocket is created and the test discs are inserted in a position (a) above or (b) below the periosteum. The borders of the incision are sutured together with 4-0silk.
* The word “inducing” has been used by the authors for lack of a better term to describe the process that is taking place. Actually, it is not known whether bone grows into the materials because of induction, or simply because it is allowed to grow in.
BONE GROWTH
3
TABLE I Supraperiosteally Implanted Discs 10 Weeks
RPG carbon- carbon 1.79 g/cc Pore size:+ 20micron
Loosely ~ t t a r h e d Thin capsule to soft tissues but around disc. not to bane.
Thicker ropsule. Some vessels in capsule, some barely entering the disc. Few extrusions?
RPG carbon-carbon
Loosely attached to roft tissues but not to bone.
Some attarhment to soft tissues.
Several extrusions. Some vessels penetrating the periphery. N o bone growth?
Loosely attached to soft tissues but not to bane.
Some attachment to soft tissues. Same disrs extruded
Many extrussians. Slightly better vessel penetration than above. N o bone growth.'
0.191 g/cc 70-80 ppia
15 Weeks
30 Weeks
Materials
~~
RPG carbon-carbon 0.096 g/cc
3-60 ppia Polypropylene Pore size: 300 micron
Good attachment Tightly attached to soft tissues but to soft tissues. No not to bone.a bone growth. One extrusion?
Polyethylene Pore size: 200 micron
Good attachment to soft tissues but not to bone.a
a
Tightly attached to soft tissues. N o
bone growth."
Denotes perfusion with radio-opaque material was performed.
TABLE I1 Subperiosteally Implanted Discs Abterials
10 Weeks
15 Weeks
30 Weeks
RPG carbon-rorbon 1.79 g/cc Pore Size: *20 mtron
No attachment to bone. No bone growth.
No attachment to bone. No bone growth.
Vessels seen i n periosteum. No bone growth into the discs."
RPG carbcn-carbon ppia
Loosely attached to bone. Some osteoid ot base.
Better attarhment Osteoid at base and into matrix.
Very good attachment to bone. Mature bone ond vessels growing into dire?
RPG carbon-carbon 0.05'6 g/cc 50-60 ppia
Attached to bone but can be seporated easily.
Good attachment Mature bone at base. Matrix full with asteoid.
Excellent attachment. Bone and vessels growing a l l the way into tlp material. One extrusion
Polypropylene Pare Size : 330 micron
Loosety attached to bone. Same vesselr penetrating:
Goad attachment to bane and vessel ingrowth .Osteoid at base and matrix.a
Polyethylene Pore Slze: 206 micron
Laasety attarhed Good uttachment to bone. Some ve- to bone and vessel rsels penetrating.a ingrowth. Osteoid at base and matrix.
0.191 g/cc
70-80
a
Denotes perfusion with radio-opaque material was performed.
.-
-
4
CESTERO, SALYER, AND T0RA”I’O
200 g of Micropaque and 50 g of gelatin dissolved in 1 1. water at a temperature of 38°C and at a constant pressure of 120 mm Hg. Diameterically oriented, 1 mm thick sections of each disc, together with a portion of skull, were obtained using a high speed carborundum disc. Microradiographs were performed on 2 x 2 Kodak projector slide plates in a Faxitron (Grentz Ray) unit. Correlating histologic sections for microscopic examination were prepared by the technique described by Klawitter [7] and stained with the polychromatic stain Paragon C1306.
RESULTS All the implanted materiai that was located above the periosteum failed to show bone growth. A vascularized capsule formed around the implants (Fig. 2 ) , and usually there was little vascular penetration into the prostheses. Several of the implants in this location were extruded, usually after 15 weeks. When the prosthesis was placed as an onlay graft under the periosteum, there was good bone and blood vessel growth into all of them from the point of contact with bone. The periosteum from above contributed some vessels but no bone (Figs. 2-4). The carbon prostheses with pore s i x less than 20 p (1.79 g/cc), failed to show bone growth as was expected. Bone growth into the material, usually was anteceded by the following order of events: first, there was vessel ingrowth (mostly from the bone side) accompanied by a rather acellular ground substance, that later was replaced by osteoid in the typical lamellar pattern and eventually became calcified into mature bone. The authors suspect that this acellular substance is unorganized bone collagen and therefore have called it preosteoid. At present, we are in the process of analyzing this substance. It was also observed that most of the carbon prostheses released microparticles which migrated through the lymphatics and stained the
Fig. 2. Microradiograms of polypropylene discs after perfusion (2.5 x). (a) 10 weeks old, above the periosteum; (b) 15 weeks old, above the periosteum; (c) 10 weeks old, below the periosteum; (d) 15 weeks old, below the periosteum.
BONE GROWTH
5
Fig. 3 . 2.5 x microradiograph of a 30 weeks porous carbon (0.191 gm/cc) disc located below the periosteum. New bone (NB) shows as “cotton balls” left side. Calvarial bone (Ca) is seen on the right side. Larger periosteal vessels are indicated (Pv). Upper right corner is microphotograph of small vessels that have penetrated into the discs. (100 x).
Fig. 4. 100 x Microphotograph of a 30 weeks porous carbon (0.096 gm/cc) disc located below the periosteum. New mature bone (NB) is seen growing into the carbon (Cb) interstice. Uncalcified osteoid (Od) i s indicated by arrow.
6
CESTERO, SALYER, AND TORANTO
subcutaneous tissues. In general, early bone growth was favored by a larger pore size, but by 30 weeks the difference was minimal. There was no significant difference in the quality or quantity of bone growth that could be attributed to material differences other than pore size. DISCUSSION Bone accompanied by blood vessels grows into porous carbon as well as into polyethylene and polypropylene when placed as onlay grafts if the pores are of adequate size. The material studied did not perform to our satisfaction in the soft tissues. There seems to be a future in reconstructive bone surgery for these materials, especially the plastic ones. The extreme brittleness of the carbon, as well as its tendency to release small particles that stain the tissues, makes the carbon less desirable even though design improvements could make it more suitable. Both porous polyethylene and polypropylene discs showed about the same osseous growth and vascular penetration qualities. I n addition, they are more elastic and resistant to impact. Their consistency allows cutting with a knife to mold them at the operating table, even though a preformed prosthesis from a preoperative mold cast from the defect seems preferable. Long term degradation by the physiological environment and tissue (bone) reaction studies as well as bonematerial stress resistance studies should be performed before they are freely used in clinical application. Another interesting observation is that in all prosthesis, bone failed to grow from either side of the periosteum, even though the same prostheses showed bone growth from the side that was in contact with bone. This is in disagreement with the general belief that periosteum generates bone. CONCLUSIONS Bone and blood vessels will grow into porous carbon and plastic prostheses placed as onlay grafts. Pore size is a very important factor. The carbon prostheses with larger pore sizes, 70 to 80 ppia and 50 to 60 ppia, gave satisfactory growth; the carbon prostheses with the smallest pore size, 20 p , did not. Polyethylene (pore size 200 p) and polypropylene (pore size 300 p) gave adequate results. Soft tissue fixation is unsatisfactory, especially for porous carbon, which showed a high tendency to extrusion. The plastic prostheses were not in place long enough to establish a soft tissue pattern, as most carbon extrusions came after 15 weeks. The periosteum failed to show bone generation capacity in this experiment. This study was supported by the Plastic Surgery Research Facility, Veteran’s Hospital, Dallas, Texas, and the Southern Medical Association.
BONE GROWTH
7
The authors wish to express their appreciation to Joan Kmetz for her valuable assistance in writing this paper. They are also indebted to Jerome J . Klawitter, Ph. D., for his contribution. The RPG porous carbon produced by Super-Temp, Inc., and the porous polyethylene and polypropylene produced by Porex, Inc., Fairburn, Georgia, were provided by Zimmer U.S.A., who also provided for the sectioning of the implanted material.
References [I] H. Yamada, in Strength of Biological Materials, F. G . Evans, ed., Williams & Wilkins Co., Baltimore, 1970. [2] T. S. Leeson and C . R. Leeson, Histology, W. B. Saunders Co., Philadelphia, 1970. [3] L. Smith, Arch. Surg. 87, 653 (1963). [4] S. F. Hulbert, “use of ceramics in surgical implants,” paper present at Biomaterials-The Case for Ceramics Symp. Clemson University, Clemson, South Carolina, 1969. [5] M. J. Lapitsky, Investigation of Bone Ingrowth in Porous Carbons, M . S. Thesis, University of Washington, Seattle, Wash. (1972). [ 6 ] B. W. Sauer, J. J. Klawitter, S. F. Hulbert, R. B . Leonard, and J. G. Bagwell, “The role of porous polymeric materials in prosthesis attachment,” paper the 5th Annu. Biomater. Symp. Clemson University, Clemson, South Carolina, 1972. [7] J. J . Klawitter, “Attachment of prostheses by bone growth into porous materials-techniques for microstructural evaluation,” paper presented at Amer. Acad. Orthopedic Surgeons, Las Vegas, Nevada, 1973.
