CA2181139A1

CA2181139A1 - Cranio-maxillofacial bone defect repair

Info

Publication number: CA2181139A1
Application number: CA002181139A
Authority: CA
Inventors: Craig D. Friedman
Original assignee: Individual
Current assignee: American Medical Electronics Inc
Priority date: 1994-01-28
Filing date: 1995-01-27
Publication date: 1995-08-03
Also published as: EP0741551A1; AU1732595A; WO1995020368A1; EP0741551A4; US5503164A

Abstract

An apparatus for the repair of craniomaxillofacial bony defects is described comprising a bio-compatible scaffolding (12) with an insert segment (13) positioned at the proximal surface of the bone defect and stabilized with support means (15), coupled with bone replacement material (21a) applied distal to the scaffolding insert segment (13) and generally filling the defect. Most preferably, the bone replacement material (21a) is a low temperature hardening, gradually resorbable hydroxyapatite forming cement. Also taught are surgical methods for the repair of cranio-maxillofacial bony defects employing the scaffolding and the bone replacement material; and kits including the scaffolding and material are included.

Description

wogsl20368 218~ ~ 3~ r~lm~ ~ loos CRANIO-MAX~LLOFACIAL BONE DEFECT REPAIR
RA(~K('IROT~I~D OF TF~, T~ ~O~
Fif~ f th~ TnvPntinn s This imvention relates to the repair of bone defects in the cranium or in facial or r 1 bones. In particular, it relates to a specific restorative .... of rr ~ ~ and bone t~ ' material which is used to repair such defects, to tbe rr ~ g itself, and to the associated methods, wrgical ~ ' , , medical devices and kits.
0 ~S~;' Of thP prirlr Art A variety of devices and materials have been used in attempts to repair bone defects. Metal plates have been employed to repair cranial defects for centuries. However, contour .~. '~ ;.. of the non-stress-bearing " ' ' skeleton continues to be a technical and materials science 5 problem. Metals are difficult to shape and are hampered by ;' ~ v ~ ~ such as infection and corrosion. Polymers are often ~ , ' ' by scar tissue, resulting im significant rates of implant infection and/or extrusion. Autogenousbone grafts and other biological materials may cause donor site morbidity, may exhibit significant post .' resorption, and are L.._'' to 20 accurately form to skeletal defects.
Of the alloplastic materials used to augment and replace the skeleton, the most promising and best tolerated are calcium phosphate-based ~ . ' Smce the mid-1970's, a variety of preformed calcium phosphate materials in the form of h~d~u~ r have been used in 2s clinical ~ withiu meoicine and dentistry. To some extent, the ty of these lJ~ - has been limited because they had to be preformed as hard materials. These ceramic forms of llrd.u,.~ e are heated to fuse individual crystals to each other through a process called sintering. This results in a tough, r ~ o.. ~_DulllalJlc material 30 available in dense or porous forms. See Costantino and Friedman et al., 2181 t~

"Hycllu~y~dLit~, Cement: I. Basic Chemistry and Histologic Propercies," 117 Arch. OLc,l~ ~ 1 Head Neck Surg. 379 (April 1991).
Most of these implants have been in the form of ~JIc q ' l, sintered hy~ul~y~u~ in eitlher granule or block forms. These l~L~ have s several drawbacks, ircluding a lirnitec1 ability to conform to skeletal defects, LiLuLuly in the case of blocks; inadequate structural integrity of granules (which do not bond ~:ogether), and difficulty in modeling the implant to the shape of missing skeletal tissue with both blocks and granules. The block form of h~JIu,.y~l~JdLiLc provides structural support, but among other ~
must be held in place by means, which greatly lirnits its use and its cosmetic results; and it is very difficult to saw a shape such that it fits the patient's individual defect. The granular form produces . lly better results, but has a very limited structural stability and is difficult to containduring and after a surgical procedure. All of these products are ceramics, 5 produced by high t~ ' C. sintering, and are not -vicl~ldlly crystalline, but rather have their crystal boundaries fused together. These ceramic-type materials are in general ~ , I,.ul~,;~ non-absorbable (having an absorption rate generally not exceeding on the orde~ of 1% per year).
A porous, nù.. ._D~,II,d~l., material based on coral allows ~ u.. Il-20 with bone, but ultimately becomes only d,U~ / 20% bone with theremainmg 8û% subsisting as scar tissue. "HA RESORB" made by Osteogen is a form of absorbable apatite, but is not a cement and is not entirely composed of llydluliy~ it~. It is grmular and not adhesive. "HA RESORB"
is loosely rather than adhesively packed into place. It is resorbed quickly and ~s may result in defect formation. In the dental materials market, ~HAPSET" is a I , of calcium phosphate granules amd ' ' plaster of Paris (calcium sulfate). This material is not truly a hJd~u~y~dtiLc; cement and contains too much calcium sulfate for most biological uæs. The calcium 2 ~ P~ 5~IOO9 suhfate component of such a ~ is resorbable, but not the calcium phosphate gr,mules.
One alternative which has been proposed is a composite formed of a metal, such as titanium, tantalum or niobium, mixed as a powder 5 with powdered ceramic calcium ~ ' ,' and then pressed or simtered into an implant. See U.S. Patent No. 4,599,085 (Riess et al.).
A specific but fairly common bone repair problem in the cranial area is the repair of burr holes af~er a I .~. Burr hole defects after L ... : .y can easily be detected by the naked eye shortly after an operation;
they may cause retraction of the skin and are . lly 1~n~ ng Thus, im modern _ l operations, the repair of burr holes is an important end step to the .~.
Attempts at burr hole repair have imcluded the use of different metals such as aluminum, gold, vitallium, tantalum and stainless steel. Also, 5 ço--.p~ of plastic, acrylic resin and ceramics have been employed.
Frozen Iyophihzed human cadaver bone, chips of _ , bone, and coral have been used to fill burr holes. Attempted plugging of burr holes with autologous bone plugs formed with rongeur, mostly from the temporal bone, is another technique that has been employed. All of these a~ x~ have 20 been ~ y to some degree. Local irritation, failure to achieve good cosmetic results, additional surgical time or ~ sources of cylindrical bone plugs have been some of the difficulties ~ I Use of a specialized burr hole saw for " production of burr holes and autologous bone plugs which can readily be reinserted and locked 2s in place using bone dust and Tiscel glue has also been described. Bostrom et al., "R~o..~ of t' ~ Burr-Holes with Autologous Bone Blugs Lsic] Made by a New Hole-Saw," 105 Acta Neurochir. 132 (1990). Examples of metal plates for burr hole repair, by bridging the outer surface of the defect are the micro burr hole covering and bone fiap fixation plates from Leibinger WO 95120368 ~ J,.,S.~1009 ~181 l~q ~

GmbH. See "Titanium Micro System," Leibinger GmbH 1992 Titdnium micromesh for defe~t-bridging outer surface of bony structnres is illustrdted in the same brochure. See also the larger scale "DUMBACH
TITAN MESH-SYS1~M" ("DTM") of Osw. Leibinger GmbH (1990), which s may be employed with ,, spongiosa, granulated ~' 1i7,~A
pyrolized bone and ~lyVlU~ aL;t~. granu~ate if desired.
Recently, a new type of calcium phosphdte cement that sets to h~J~u~, m vivo hds been developed. See U.S. Pdtents Nos. Re. 33,221 and Re. 33,161 to Brown and Chow. This is essentially a bone l.r'?
10 or bone substitute ce~nen; which cdn be applied , ~ as a paste and , sets to a ~ "~, stable impldnt material composed of IVIV~... h~Lv~-~, This is a form of h~Lv~a~Jd~;t~, cement which is produced by direct .,.~ " of ~Jlv~, in vivo, and does not require hedting for the formation of a "y stable implant.
15 These new h~Jlw~,a~Jd~i~ forming cements are biologically compatlble and are self-hardening to form a mass with sufficient strength for many medical and dental ~, " When implanted im bone, the cement resorbs slowly and is gradually replaced by new bone formation with negligible loss in the volume or integrity of the ~issue that receives the implant. See also U.S. Patent 20 ~,,'' " Serial Mo. 0~/030,709, filed ~Idrch 13, 1993. The material of Brown and Chow has been employed, e.g., to reconstruct two centimeter diameter calvarial defects in cats. The calcium phosphate cement was gradually replaced by bone, mstead of being fully resorbed without bone deposition or remâining as a permanent impl;mt. See Chow, Tal~agi, 25 Costantino and Friedman, "Self-Setting Calcium Phosphate Cements," 179 Mât. Res. Soc. Symp. Proc. 3 (1991). A virtually identical calcium phosphate system which consists of ~ r~11 phosphate and ' phosphate or its ' J.' form was described by Constant7 et al. (Compare U;S.
Patents Nos. 5,053,212; 5,129,905 and 5,178,845). This cement system is W0 95/20368 ~ iO09 2 1 ~
s believed to involve, in some ~ ' , conversion of the - ~
phosphate to dicalcium phosphate which reacts with i ' phosphate to form h.~u~ .
ST~MMARY OF rl'l~F INVP.~l'r(')~
s It has now been discovered that the repair of many bony defects may be improved through the use of a - , ' ' S~rr~
with an imsert segment positioned at the proximal surface of the bone defect and stabilized with support means, coupled with a bone 1 l- material applied distal to the q ' ' " insert segment and generally filling the defect.
o Most preferably, the bone l~ir' material is a bone , I~ cement applied in paste form.
One aspect of the invention is an apparatus ~ a ~rr~ to support a bone . '; material for the repair of, .. r ~ bone defects, where the rr ~ is of a I 1~ , ' ' material and comprises an s insert segment that is relatively thin compared to the depth of the defect and which a~ in contour and in ' of its perimeter the proximal surface of the missing bone. r~he apparatus further comprises means to support the insert segment m its desired position at the proximal bone surface of the defect. More preferably, the insert segment is comprised of a 20 L- . ''- metal, metal oxide or metal aUoy and the apparatus further comprises a ' ' segment which is relatively thin compared to the depth of the defect and is disposed at least in part on the distal surface of the bone '- ~ the defect. Often, the ' ' segrnent will be in a plane roughly paraUel to the insert segment. rrhe apparatus also comprises a 2s coMecting segment, which is preferably ~ / P 1~ to the planes of both insert and ' ' segments, and which coMects the insert segment to the ~ . segment so that the pPrrPnrlir~ r distance between the two is less than, or more preferably about equal to the depth of the 'l'lf~ 1 bone defect. The preferred material for the scaffolding is WO 95120368 }'~ 1009 t~

comprised of titanium~ iCII h, and, most preferably, the insert segment, ~ ' segment and connecting segment are all formed from a unitary piece of titanium .uh, The imvention further ,' a composite comprising the S ! rr~ apparatus having its imsert segment overlayed with the bone material contoured to fll the space bounded by the sidewalls of the ~ r 1 b~ne defect, the insert segment of the ~ ' ' ~ amd the distal surface of the defect. Examples of bone , '~ materials useful in the imvention include calcium phosphate based materials, silicate acrylic salts,o sintered h~Lv~a~J~Litc grmules, ~ r~ ' ' (or corraline) h~u~ c, apatite gr~mules and ~ polymers. The bone , ' material is preferably a I I ' ' self-setting at least partially resorbable h~Lu~tik cement; and the scaffolding is preferably comprised of an, , vc metal, most preferably titanium.
The invention further includes a surgical method for the repair of ' bone defects, ~ ul~ly full tniclcness 1InfD~
skeletal defects comprising inserting the imsert segment of a scaffolding apparatus into the defect with the insert segment ~ , flush with the base of the defect, affixmg tne cr~ , to the i~UII~ bone with 20' ' " ' means, filling the remainder of the defect with bone material, and contouring the material as ne~ded to rr ' ' the distal surface of the missing bone. In arl additional ' ' t, the invention comprises a kit irlcluding the scaf~folding and the bone lcr'; material, and/or starting materials for their 1~
2s The apparatus and ~nethod may be employed to repair a variety of I defects, especially full tnickness ~ - ~InfD~iDl skeletal defects, ~ , b~rr holes.
A number of objects and advantages ~ .. .; . the imvention. The inventive apparatus an~ method provide a ~ ' ' ~, i.e., floor or grid, upon .

wo ss/2036s 2 1 8 1 ~ 3 9 r~ s i ~s which the bone l 17 material to repair a~' ~ 1 bone defects is applied. While, e.g., bone ~' cement paste may be used to fill cranial burr holes directly, if there is not dura directly below the burr hole, the cement can extrude 'Iy, The ~rr, 1 insert segment prevents overfiDing "y.
The inventive apparatus aad surgical technique are also easy to use and convenient for the surgeon r -~ . Burr holes aad other similar cranial defects can be rapidly filled with bone rl material in just a few seconds. Ia the case of burr holes, the invention reliably aDows 14 miDimeter burr holes to be filled by 2 to 2.5 grams of self-setting h.~u~, cement. In addition, the bone . ~' material when applied over the rr ~ ' ,, achieves the a,U,ulul contour, ~ h- ` the area, and seals the ' space from the;
A further advaatage of the inventive apparatus is that it does not require that screws be used to hold the iasert segment ia place. When a bone cement is used, fixation of the ,~ul~.t may be achieved by the cement as and after it sets. However, other support means, including screw fixation of extensions or tabs connected to the insert segment, are also , . .
RRrF.F D~RTprl()N OF 1~, Dl~Aw~
FIGURE IA illustrates in l~ ~C~,Liv~ a cranial defect with an of the inventive S~ " in position.
FIGURE IB is a top view of the Sr~ in position, iDustrating metal micromesh material for forming the ~r~
F~GURE lC depicts the deposition of bone ~ cement paste materi~l in the space bounded by the ~ _~1. ~ insert segment and the sidewalls of the bony defect.

;~8~ ~3~ ~
g FIGURE lD i~lustrates the completed bony defect repair with the distal surface of the bone l ~ material contoured and smoothed to replicate the contour of tbe distal surface of bone miss~ng at the defect.
FIGURE 2 is a p~.D~ live view of a burr hole repaired in r 5 with the invention; the ~ segment comprises two tapered tabs fLxed into the healthy bonæ with metal screws. The bone .- cement illustrated in thiD figure is partially cut away to pennit vjc~ 7r~inn of the entire inventive appa~atus.
F[GURE 3 is a ~ID~L~ view of a ~ ' " ~ with a unitary loop for lo receipt of a metal !- ' "' ' screw. This ~ ' " ~ is again placed in a burr hole amd the bone ,' material is padially cut away to better illustrate the combimed apparatus.
FIGURE 4 shows a scaffolding with ~ segments comprising flange means that are relatively stiff, but bendable under manual pressure, and 5 biased against ~ 'y opposmg sidewalls of the bony defect so as to fonn a resilient ' ' means for the c.~ff~ while the cement paste is inserted.
F~GURE S illllstrates the inventive repair apparatus in an; ' in which the perimel~er of the bony defect and the perimeter of the insert 20 segment are ~ID~ the insert segment itself is perforated im an ~DJ ' ' ~ pattern, and more than two ~- " means, in the form of tabs ~ , onto the distal surface of the periphe~l bone, are employed.
FIGURE 6 ;llustrates the mvention in a different area of the r ' 1 skeleton, namely, the orbital rim.
2s E:IGURE 7 depicts an alternative burr hole repair r~
FIGURE 8 slhows an i ' " of an imventive kit comprising scaffolding and bone r~ ' material.

woss/20368 2 ~ 3~ PCT/US95/01009 DP-~RrpIIoN OF 1~ I'K~ khl) ~MR-)D~MP.1`1TS
The complete disclosures of U.S. Patents Nos. Re. 33,221 and Re.
33 ,161 and pending U. S . patent ~ r~inn Serial No. 08/030,709, filed March 13, 1993, are expressly r ' ~ herein by reference.
s Refer~ing to FIGURES lA and lB, the ~ ~1r,f~r;Al bone 10 sustains a defect 11. The defect depicted im the FIG~JRE is a butr hole, but the invention is suitable for repair of other ~- r ' 1 defects, e.g., at tbe orbital floor, orbital tim, mastoids, maxiUa and ~ 1. The inventive .~r~f.fr' 1' ~, generaUy 12, is seated in the defect with a relatively thin insert segment 13 having . ~ and contour of its perimeter 14 ~
the proximal sutface of the missing bone. Means, generaUy 15, are employed for supporting the insert segment in position at the proximal bone surface of tbe defect 20b. In FIGURE lA and lB, the supporing means are iUustrated as a r ' - segment or tab 16, shown im the figure as ~ , which laps over onto the distal surface of the cranium in one or more positions at theedge of the defect. The ~ l;., segment 16 is attached to the msert segment 13 of the ~. ~rr"1 1 ~f; 12 by commecting segment 17. C. l~, segment 17 is relatively tigid and ~ to the plane of the insett and ' " segments. The entire ;~ , includimg imsert 20 segments and suppott means is prefetably formed of a l: . ' ' metaUic mesh 18. The ~ ' " ,, insert segment 13 together with the sidewalls of the bony defect 19, and the distA~ surface of tbe defect where bone was previously present or should have been present 20a, deflne the space for insettion of the bone r~ ' material.
FIGURE lB provides a p~r~n~lirlllAr top view of the s~ ' " ,, in one ~I./b~ ' in which the D~ is formed of the prefer~ed titAnium micromesh. Most preferably, the micromesh is of .1 to .2 thickness; i.e., it is telatively thin compared to the depth of the bony defect in -- for which this repair is suited.

WO ssno36s pcrnJsssloloos ~81 1~ ~

The method of the invention, see FIGURE lC, is a surgical method for the repair of a ~ bone defect ~ inserting the scaffolding desclibed :3bove imto the bony defect 11 with the insert segment 13 alJ~n~ flush with the proximal base of the defect 20b, stabilizing the scaffolding to the , ~ bone with ' - means 15, flljng the remainder of the defect with bone ~ material 21a, and contouring it a~
The composite , ~ the scaffolding apparatus with boDe IC, 1l ' material in place 21b, contoured and hardening is illustrated in FIGURE lD.
With reference to PIGURE 2, the scaffolding 22 may compnse a variety of means for stabilizillg the insert segment 13 at the proximal surface of the bony defect 20b. An alternative to the ~ ' overlap tabs 16 of FIGURE
1 is illustrated as tape~ ed overlap tabs 23 in FIGURE 2 which lie on the distalsurface of the cranium at the perimeter of the defect and are fixed in place with screws 24, preferably of metal or metal alloy. In the figure, the inventive scaffolding is seated im a burr hole and bone r ~ ' cement 21b has been partially cut away in the figure to better illustrate the invention.
FIGIlRE 3 ;11ulstrates aDother alternative, ' ' of the invention in which the rr ~ " g 25 comprises an insert segmeDt which is a plate 26 imtegrally forrned Witlbl a projection and screw seat 27 which together with thescrew 28 affixes the scaffolding to the bone near the defect and stabili7es it in position. The bone IC. '~ r~aterial 21b is once again cut away in the figure for illustrative purposes.
In FIGURE 4~ a scaffolding 29 is seated in a, - r ' ~ defect in a~, with the invent~on and is stabilized in position by the externally biased resilient perimeter of the insert segment, or a portion thereof, bent distally. In tbe figure, cement 21a is in the process of being poured, injected,squirted, spatulated, s]~ooned or otherwise introduced into the defect on top Of 218t f39 Il the _rr ~ ~ and will itself serve as a principal aspect of the means for stabili~ing the ! __rr_~ , in the desired position. The cement also serves this purpose in other e_ ~ ' of the invention.
As shown in FIGURE 5, neither the ~ r ' I defect nor the 5 .cr~ff~ need be ~ ' for pu poses of the imvention. r~his figure depicts an ~ ' bony defffl with an ~ . . . rr ~ ~- I 31. The perimeter 32 of the inlet segment ~ the perimeter of the defect. In addition, the insert segment of the S~rr,~ may be ~ "y perforated. The means for stabil~ing the imsert segment in this o comprises multiple tabs 34 which are relatively rigidly comlected to the imsert segment with commecting segments roughly pCI~ li ' to the insert segment's plane and which are bent at 90 degrees at a height equal to tbe depth of the crarial defect so as to form ~.. ' ll ., tabs on the surface of the bone peripheral to the defect.
FIGllRE 6 illustrates the preferred; ' ' of the invention in this case applied to repair a defect im another r ~ location ~amely, tbe orbital rim. In FIGURE 6, a defect 33 in the orbital rim 34 is fitted with a preferred C~ff-~ 35, , ~ a ...h~l~ ' insert segment 36 d~ '-1" the proximal surface of the missing oone in ~ r '- and 20 contour. Slotted flanges or loop shaped extensions 37 attached to the imsert segment comprise a supporting means 38 and are bendable anywhere along tbeir length to form tbe ct~llili7~ti-~n seglnent and conmecting segment. Tbe ~' of tbe slots in the flanges or extensions are suitable for receipt of screws employed in r ~ bone repair. Tbe threaded portion of 2s the screw can pass tbrough tbe opening, while the head of tbe screw is too Iarge to fit through the opening and thus anchors the loop shaped extension m place.
FIGURE 7 illustrates a burr hole repair .c~ 39 witb insert segment 40 and with suppor~ing means 41 extending tberefrom, and also WO 95/20368 PCT/US9~/O1009 including a connected grid 42 of screw receiving ports 43 containing screws 44. The preferrv~ for the holes in the ~11('" v both in the insert segment and in the ' - segme~its are from I to 1.2 mm.
FIGURE 8 illustrates an . b~ " of the conlents of an inventive kit 5 for tbe repair of -. r 1 defects: v a selection of one or more ~ rr~ 45 and a bone , ' material for use therewith 46 in an a~U,UI~, ' container 47. The kit may also contain, for eAample, other items which may be useful or convenient for the surgeon such as tools for trimming (e.g., knife or scissors), bending or inserLng the S rr~ 48, 10 delivery me~ms 49 (e.g. syringe, spatula, spoon, squeeze tube) for the bone ' material, a liquid phase 50 for r '' of a bone , ' cement from a powdered bone .' cement precursor, additives 50 which may be useful ~,vith tlle bone .,~ material in specific situations, such as antibiotics, bone growth proteins, viscosity modifiers, ' 15 bone, bone dust, etc.
A wide variety of choices is available for the insert segment of the scaffolding or platforln which is recessed within the bone defect amd acts as a floor upon which the vone , ' material can be applied. Any metal or other substance which is used should be 1 , '' Examples of 20 a,ulul~, materials include metals and metal alloys, ceramics, oAides, and preformed impl~mts of bone , I; cement. EAamples of metals which may be used include surgical stainless steel, vitaDium, cobalt-lllol.~' aUoys, titanium and t;tanium alloys, e.g., titanium aluminum aUoy. Ceramic rr1~'V may for eAample be made of calcium phosphate (e.g., 25 h.~.LUA~ Lt~, tricalcium phosphate) silicate, aluminum oAide, or ' of materials. The preferred materials for the scaffolding are ~, and the most preferred material is titanium.
The form of tlle insert segment or platform may be any - lly and biologicaUy suitable form, includmg that of a plate, a perforated plate, a woss/20368 2 1 8 1 1 3 9 PCT~U595/01009 mesh, a relatively tmn plug, a screen, or a grid. The z' means may be formed of the same material as the insert segment of the ,~rr, , or may be of different ~ , ' ' materials. The inventive ~rr~ and its parts can be comprised of a smgle l.:.~. .~.-~;l.l~ material such as the preferred S titanium mesh, or of two or more materials. The most preferred ,( ~ ' " ~
material is titanium . b, such as the titanium , ' described above available from Leibmger GmbH.
Bone - r~- materials useful in the invention include calcium phosphate based materials such hrLVA.~ ~ cements, silicate acrylic salts such as Ionos cement, sintered h.~dlVA.~, "' granules, ,~ r (or corraline) llyLvA~ ~ ~ apatite granules such as those of Osteogen and , ~ polymers (available in Europe from DTI
C, ' )-The bone , ~ or bone substitute cement which is preferably 15 employed as an aspect of this invention is of the variety of calcium phosphate-based cements which self-harden ~ lly to l~ ,lV~ Di..~" ' ' ' h~UA~ it., at a , ~, tolerable to body tissues, is ' ~, and gradually r~ o, and is gladuaDy replaced at least in significant part on a rougbly one to one basis by bone when placed im contact with living bone.
20 The term "low ~ gradually resorbable hyV;VA~ JaLilt;
forming cement" wiD be employed hereinafter to refer to this material.
A preferred cement is that of Brown and Chow described in U.S.
Patents Nos. Re. 33,161 and 33,221. The preferred major, , of the calcium phosphate cement of Brown and Chow are tPt~:ll phosphate 2s (TTCP) and dicalcium phosphate anhydrous (DCPA) or dicalcium phosphate dihydrate (DCPD). These react in an aqueous ~1.. u~ to form hJLvA~ Lit~, OEIA), the prmcipal mineral component of teeth and bones, as the fmal product.

WO 95~20368 2 ~ 8 I t 3 q PCI/US9S/01009 The chemical r~action that occurs during the setting of the TTCP-DCPA
(or 'rTCP-DCPD) cement described in Brown and Chow can be ~ J., ' by the followimg equatior~:
Ca4(PO~O + CaHPO~ ( 2H2O) -----~ Ca~(PO~)3OH + (2H~O) s 'rTCP DCPA [DCPD] HA
Rapid HA formation and: dissolution of both cement , "
ITCP and DCPA, lead to the hardening of the cemeDt ordinarily within 30 minutes or less.
Most preferred are the improved bone r~ ' cements described 0 as follows in p~nding U.S. patent application Serial No. 08/030,709, filed March 12, 1993, which . , use of I ' phosphate precursor that has been maintained in a relatively anhydrous ~ prior to its use, and/or prepared with a calcium to l - , ratio of less than 2 %:
According to Se~ial No. 08/030,709, if the prepared 15 phosphate has a molat Ca/P ratio above 2, calcium oxide is believed to be present in the material as an impurity phase. When such a;
phosphate sample is used in the cement. the rapid dissolution of the CaO causes the pH of the cement slurry to rise 11y above pH 8.5 (but below 12), which impedes the setting reaction.
It was also foulnd that i 1 phosphate is extremely reactive to water. Thus, when exposed to air, i phosphate has been found to react with the moisture present in the air to form a small amount of L~L~ , (O~lAp) and calcium hydroxide or calcium oxide. It was discovered that these products coat the surfaces of the i ' phosphate crystals and cause the i ' phosphate particles to become b;~ ly less reactive when used in the cement system. By ~ ' phosphate in an anhydrous ,., . u~ t, the ~ ' surface .
by the: ' ' reaction products is ' Self-setting calcium phosphate cements with 11y improved setting times and . 1 woss~2036~ 2 8 ~ ~ 3 9 PCT/US95/01009 strengths were obtained when I phosphate prepared under anhydrous conditions was used.
The I ' '- reaction of t~t~l phosphate with moisture is ih~ ,;bl~ at later stages in its 1~ A 50 that drying the ~ o~
s ' phosphate to remove the water was not found to suffice to reclaim the proper~ies of ~ ' t~rAl phosphate.
T~t-~rA1 phosphate has the formula Ca~(PO4)20, and a theoretical ideal molar Ca/P ratio of 2Ø Its traditional mode of I , - is illustrated in the following equation:
2 CaHPO4 + 2 CaCO3--> Ca4(PO4)2O + H2O ~ + 2 CO2 t (1) It is i' '.~ stable only at:, above 1400C.
InS.N.08/030,709,thepreferred1~ ;.. of ~ ' phosphate powder for cement use is illustrated by the following steps:
F ' 1 f ~otT~rs~ ?hn~ e in a fi~ One first prepares a I " mixture that has a Ca/P ratio of less than 2, heats the mixture to 1400C or above, and then maintains the sample at that . for a ~ 1~, long period of time, for example 6 hours, to aswre as complete 20 conversion as possible of the starting mixtnre to i ' phosphate. An example of the starting mixture would consist of 2 moles of CaHPO4 (272 grams) and 1.8 moles of CaCO3 (180 grams). The excess H2O and CO2 are expelled in the heating process.
One may also use any other types of calcium and phosphate containing 2s ~ , ' to prepare mixtures with a molar Ca/P ~atio of less than 2 provided that the non-calcium and non-phosphate . in the mixture c;m be expelled by ev r - during the firing with or without an r oxidation reaction. For example, the following reactions may be employed with alJyl~ ~ adjustment of the molar ratios:
.

woss/20368 2 1 ~ 1 ~ 3~ PCr/Usss/oloos 2 CaHPO" + 2 CaO ---> Ca~(PO,,),O + H20 t (2) Ca2P2O7 + 2 CaO ---> Ca~(PO2O (3) Ca3(POI)2 + Ca(OH)2---~ Ca~(PO4)20 + H20 t (4) 4 CaO + 2 (NH,~)3POl --- > Ca4(PO4)20 + 6 NH3 t + 3 H20 t (5) 52 CaHPO4 + 2 Ca(CH3COI)2 + 4 2 ---~
Ca,,(PO,,)20 + 7 H20 t + 4 C02 t (6) The ~ of the nnixture for firing is the only step in the t~'tl5~l ' phosphate synthesis in wbich the presence of water is not a concern. This is because the i ' phosphate is formed only after the firing process.
~ ' 2 (r( , ~iv~,) If the Ca/P molar ratio of the I ~, mixture prepared for firing is above 2, calcium oxide will be present as an impurity phase in the product.
rnus' in tbe reaction~ ' by equation (1), if 2 moles (272 grams) of CaHPO~ is combined with 2.2 moles a20 grams) of CaCO3, the molar Ca/P
ratio wiU be 2.1, and the reaction in the furnace wiU be:

2 CaHPO4 + 2.2 C2C03 ---~
Ca,(PO,,)2O + 0.2 CaO + M2O t + 2.2 CO2 t (7) rne presence of CaO as an impurity in the prepared t~r~ l phosphate is 20 l ' ' ' because ~uring the cement setfing, rapid dissolution of CaO rdises tne slurry pH to d~JII ' ~ 0 to 12, and tbis greatly impedes the setting reaction to tbe point that the cement often fails to harden.

.

WO95/20368 2~al ~39 PCI~/U595/01009 r ~ 3 While it is essential that Ca/P ratios of Oreater 2 should be avoided in the preferred i ' " t, a rnL~ ture with a ratio of lower than 2 is pr . ~ ;, as far as the cement setting reaction is concerned. This is because s in such a case, the reaction impurity by-product wiU be h.~dlu~ 1 It is important to note that when h.~u~a~Jdi~ is folmed dunng the f~ing process, it is l O 'y dispersed in the prepared ' phosphate as a phase impurity, and tbe reactivity of i ' phosphate is not ~ ~ ~y affected. This is in great contrast to the ~ hu~li~ coatings that form on o the ~r't~rsll ' phosphate c~ystals as a result of reaction with moisture. In this latter case, the h.~u,.~.Lt~, is highly ,'~ ' to the reactivity of ~tr: r:ll phosphate. 13quation (8) given below iUustrates the hJ~u~ ,u~Lt~, as a by-product when a mixwre with a Ca/P ratio of 1.9 is fired:

2 CaHPO4 + 1.8 CaCO3 --->
s 0.7 Ca4 (PO4)2O + 0.2 Ca~(PO4)3OH + H2O ~ + 1.8 CO2 t (8) ll~unple 4 A Ca/P ratio of 2 precisely is to be avoided because the inherent error in of the reactants makes actual r ~ of a sample with Ca/P ratio Oreater than 2 a statistical ~ ' y in a number of instances, and because cements prepared from t.'tl~r~1 phosphate with Ca/P ratio less than 2 were found to have greater ' ' strength than those with a ratio of 2, as iUustrated in the following olble:

wo 95/20368 PCr/uss~/oloos 2t~f t~9 :~, Effect of the CalP Ratio of TTCP on Diametral Tensile StrPn3~fh (DTS) of (~ m Phos~ Cement CalP Ratio of TTCP 2.0 1.96 1.90 DTS (MPa) o Mean i s.d.
(n = 3) 8.34 i 0.17 8.06 i 1.64 10.38iQ44 To prepare the calcium phosphate cement, fPf~l phosphate and dicalcium phosphate anhydrous were combined at a molar ratio of 1:1, and mixed with 25 mmol/L I ' A ~ - acid at a powder to liquid weight ratio of 4.0 at ambient tc~ a~ulc.
Diametral tensile strength was measured as follows:
DTS c 0.3 gram of calcium phosphate cement powder was mixed with 0.075 mL of hquid (powder/liquid = 4), spatulated on a glass slab for 30 sec, and placed in a stainlPss steel mold (6 mm d x 3 mm h). The top and bottom surfaces of the mold were tightly covered with glass plates and the mold was placed in a lO0 % humidity box kept at 37 for 4 hours. The sample was removed from the mold and placed in a small amount of water for 20 hours at 37. The diametral tensile strength (DTS) was measured with the use of a Universal TPstin~ Machine (United Calibration Corp., Garden Grove, CA) at a cross-head spee~ of I mm/min.
As a practical ma~ter, the CalP ratio must remain above 1.67, or ' ~dictatesthe~,.cA.a.~ ofllyL~,~aA,alilcratherthani ' -phosphate. Therefore, in this context, "less than 2" should be interpreted herein to mean less than 2 but greater than 1.67.

WO 9S/203~8 1 ~ 1009 Ex~Lmyle 5 Ouench~p of fired miyhlre jn ~n an~vdrous atmQs~here: After heating the mixture for a sufficient length of time, the mixhure must be cooled down rapidly to prevent reversion of the t~ ' phosphate to the phases that are s more stable than; ' phosphate at i ~ Iower than 1400C.
If the . ' phosphate were cooled down slowly, for example, by letting it cool down . 'y in a furnace that has been hurned off, the product obtained would contain httle t~tr/r ~l phosphate. Instead, it would be a mixhure that would _ ' " "y contain h.tJIu~, , calcium oxide, ~-~o hicalcium phosphate, ,~-hicalcium phosphate, or calcium ~,.~...' .' , depending on the Ca/P ratio and tne rate of cooling. Such a sample, if used for preparmg the cement, would yield a product with poor sehmg and sh ength properties. Therefore, quenching is necessary, and it must be done under a , anhydrous u..~ One example of a suitable anhydrous quench technique would be to place the mixture, as soon as it is no longer red hot, in a vacuum desiccator to isolate the t~h~rzll ' phosphate from moishure. Other tec~miques of anhydrous quenching available to those of skill m the alt may be used.
If the i ' phosphate is quenched in an . ' c that contains 20 moishure, a reaction illushated by equation (g) or (l0) will occur and the ~ - phosphate crystals will become coated with the reaction products, hJdlv~a~JaLit~, and Ca(OH)2 or CaO. Such a i ' phosphate sample will have poor reactivity when used in the cement r ~ .
Ca4(PO4)20 + H20 ---~ 0.667 Ca5 (P04)30H + 0.667 Ca(O~I), (9) 25 Ca,,(PO4)2O + 0.33 H20 --> 0.667 Ca5(PO4)30H + 0.667 CaO (10) Exposure to moishure at this stage will cause damage to the phosphate's reactivity to a significant extent, although not as critical as in the later stages of the l,.c~ ,lio... This is because at this point, the i phosphate is the form of chunks or lumps, with relatively small surface areas wo gs/20368 P~ I / ~. ." _. I . j 2~81 139 amenable to ~ , as compared with the . ' phosphate that has been processed to a fune-patticle state. However, moisture absorbed in the phosphate may produce an adverse effect in the process as described below.

p~Ttirl~ si7~- r~ AIlr~;nn To produce calcium phosphate cement with the desirable properties, sparingly soluble calcium phosphates of a variety and/or mixture of particle s;7es may be used. For many -rr' , it is preferred that the i ' phosphate have at least a substantial percentage of 10 particles, e.g., at least about 10%, of median particle si7e of lS ~m or below.
In some .r'- , such as ' ' an injectable root canal fller, ' phosphate with a median particle si7e of l ~m or below would be preferred. Thereforc, the particle si_e of the i ' phosphate prepared im Example 5 above needs to be reduced by ' ' means. A substantiaUy lS anhydrous L... duting the patticle si7e reduction process is critical.
SmaU samples of the tetr~ 1 phosphate may, for exarnple, be .
by hand grmding ul room air for a brief period, e.g., 5 min., but long exposure to room ah- would be, . ' ' . If the: ' phosphate is ground in a baU mill, it must be done in a closed co~tainer to isolate the 20 i ' phosphate from the large volume of moi$ room air, or in a non-aqneous liquid that has been made anhydrous. Some of the liquids that can be adv~.~.Oly employed are ~"~.' ' , dioxane, and absolute ethanol.
Other non-aqueous liquids may also be used. Traces of water in these liquids should be removed by molecular sieve or other suitable l' Liquids 2s that should not be used mclude water, 95 % etbanol, other alcohol solutions that contain water, acetone (which gene~lly contains some water), etc. If one of the latter liquids is used, the ground i ' phosphate wiU contain poorly crystaUi_ed hJdluA~ dLi~ and calcium hydroxide or calcium oxide. Such a sample will prodnce a poor quality cement or a cement mixture that wiU not 2~81 139 harden. Once the ground h ' phosphate is exposed to moisture and the reaction products coat the tPt~r~ m phosphate crystal surfaces, the reactivity of the tt~'t~r~l ' phosphate sample camnot be ; ~. ' at this point by heating and removing the adsorbed moisture.
s As mentioned earlier, if the ~ ' i ' phosphate contains absorbed moisture, because of the limited surface area, the ddmage to the i ' phosphate's reactivity as a result of h~Lu~d~ coating formation would be significant but perhaps not critical. However, ~hen such a l ' phosphate sample is ~- ' in an anhydrous liquid, the moisture released from the ~ phosphate into the liquid will facibtate the, ' ' ' reaction depicted by equation (9) or (10). This usually will render the ~Ptr~r~l phosphate unusable for ceme~t r~
If it is suspected that the . ' ~ ' phosphate has been exposed to moisture, and it is to be ground in an anhydrous liquid, it should be heated at 200C for 24 hours to remove absorbed moisture and cooled to room i A ' ~ in an anhydrous L.~.' before grinding.
,~t(l~pP, of P ~~~~ ' m phos~hate. It is impor~ant that the ground i ' phosphate be stored in an anhydrous .,~
20Becimse the ground; ' phosphate would have relatively la~e surface area, surface . by the reaction products with moisture wiD
! ' ' " 'IY 1 the reactivity of the i ' phosphate and the quality of the cement. Once the surface ~ products are formed in wbstantial quantities, the reactivity of the ~ ' phosphate cannot be 25 1~; ~. ' ' by heating.
The .' ' effects of moist TTCP o~ the diametral tensile strength of the set cement are illustrated by Table Il.

w0 ss/2036s ~ _ 1 1 ) ..,_. 1 . ~ 3 ~2 Diametral Tensile Strength of Calcium Phosphate Cement Prepared with T, ' Phosphate that Had Been Exposed to 1009i Humidity for 5 Different Lengths of Time Length of Exposure Diametral Tensile Strength in Days + s.d. (n = 3) in MPa o 0 10.38 i 0 44 0.2 8.71 ~t 0.10 7.85 i 0.13 2 6.66 _ 0.25 6.26 i 0.07 16 2.63 :t 0.24 Calcium pho3phate cement powders were prepared by thorough mixing 20 of 3.66 glams of ~ ' phosphate and 1.36 grams of dicalcium phosphate. The i ' phosphate had a median particle size of 10.2 ,um and had been exposed to humid air for various periods as indicated. The dicalcium phosphate had a median particle size of 0.8 ~m. The diametral tensile strengths were measured following the same procedure as described ~s earlier.
Additional properties of improved calcium phosphate cement as compared with the original calcium phosphate cement of Brown and Chow are listed in Table m:

~1 8~
23 ~ -~ml Improved CPC Original CPC
(ITCP Ca/P = 1.90; anhydrous prep) ClTCPCa/P = 2.0) r~ , strength 64.8 i .8 MPa 36.0 i: 7 n = 3) (n = 5) (Fukase, 1990)2 Diametral strength 13.1 i 1.3 MPa 6.9 i .3 (n = 8) (n = 5) Setting time: 14 min. 25 Gilmore needle method (Brown amd Chow, 1986)S
,=, Moles l'rCP: Moles DCPA = 1:1, powderlliquid (by wt.) = 4.0, liquid phase = 25 mmoVL H3PO~, testing conditions as per Example 4.
20 2 Fukase et al., "Setting Reactions and Cv.~ oo;~ Strengths of Calcium Phosphate Cements," J. Dent. Res. 69(12):1852-56 (1990).

3 Brown, W.E. and Chow, L.C. (1988): A New Calcium Phosphate, Water Setting Cement, ~ p cPqrrh Prl~Pcc 1986, P.W. Brown, Ed., Westerville, Ohio: Americm Ceramic Society, pp. 352-379.
As will be recognized by those of s~ll in the art, other specific techniques for, . of the i ' phosphate component of this cement may be employed so long as the calcium to phosphate ratio of the phosphate is less t_an two, and/or the 1~
30 once the i ' phosphate has been, d) is ~ ' 'ly anhydrous. While either the ' ' reduction in calcium to phosphate ratio or anhydrous IJ', will improve the setting time and quality of the L~dl~,A~ ,d~ cement, the best results are obtained when both methods are practiced together. The methods can be safely practiced im a laboratory or r ' ' ~ faci'dty without imposing excessive additional expenses. The new methods of ~ - of tPrrq~ql phosp_ate produce cements with woss/20368 2~8~ ~q r~l,u~ loos shorter and more consistent setting times and ' lly greater strengths.
The calcium phosphate cement is preferably prepared from the l phosphate described above and one or more additional sparingly 5 soluble calcium l' , ~ ' 'y dicalcium phosphate anhydrous.
dicalcium phosphate dihydrate, ~-tricalcium phosphate"B-tricalcium phosphate, amorohous calcium phosphate, and ort7~1 ' phosphate. Most preferably, ' phosphate is employed with dicalcium phosphate anhydrous or dicalcium phosphate dihydrate. The invention is practiced when the o j l - phosphate employed with the second spa}ingly soluble calcium phosphate compound is prepared in ' with these conditions whether or not it is generated in situ from other precursors or passes through chemical ' These . , ' are . l ' ' as palt of the ~ .
regardless of the ' ~i used to identify them, e.g., "calcium deficient calcium phosphate ~ 1 ' " instead of dicalcium phosphate.
The specially prepared ~ ' phosphate and other sparingly soluble calcium phosphate compound(s) are combined with a liquid phase to form the useful cem0nt, paste or slurry. The liquid phase is aqueous at least in palt and may typically be water, saline, blood, dilute ~' . ' acid, or 20 one of the above with the addition of up to 10% of a calcium or phosphate source in the calcium phosphate cement powder or im the liquid phase itself.
In situ liquid, e.g., at a wound site, c m suffice.
~amDle 8 Additional calcium phosphate cement . l that consisted of 25 TTCP prepared as described above and one other calcium phosphate from the group consisting of ~-tlicalcium phosphate (cY-TCP), ~-tricalcium phosphate (,B-TCP), amolphous calcium phosphate (ACP), and o~ ~l phosphate (OCP) were prepared with a liquid phase of 1.5 mol/L Na2HPO4. This phosphate level in the liquid phase c~n be attained by adding up to 10% of a phosphate wo 9s/20368 P_llu~
2181 1~9 2s salt in the calcium phosphate cement powder as described in U.S. Patents Nos.
Re. 33,161 and 33,221. Propefies of calcium phosphate cements that consisted of TTCP and a cal~ium pho~phate other than DCPA or DCPD are given im Table IV below.
_ Ta~le IV
DTS2, MPa setting time Solid component P/L' (mean i s.d.; n = 3) (min) TTCP3 + 2 a-TCP 3 1.29 ~ .26 25 TTCP3 + 2 ~-TCP 3 0.22 i .17 90 TTCP3 + 2 ACP 2.5 0.88 _ .11 15 3 TTCP3 + 2 OCP 3 0.48 i .06 90 20 I Powder to liquid ratio (by weight) 2 Diametral tensile strength 3 Ca/P= 1.90 The above calcium phosphate cement r~ ~ while not preferred because of their relatively low strengths, did harden. Some , J.. ' in 25 strengths are likely with adjustment of paficle size, powder to liquid ratio and other ~ These r ~ '- did not set quickly, e.g., 2 hours, when water, saline, or a dilute ~ acid was used as the liquid phase im place of the 1.5 mol/L Na2~PO~.
Generally, the preferred cement will be comprised of an equimolar 30 mixture of t~tr~ phosphate ~md dicalcium phosphate, although TTCP/dicalcium phosphate ratios may range from 1:1 to aoout 1:4. Calcium phosphate cement that bas a TTCP/DCPA ratio of 1.0 will have the y of ll.rJl~ ya~d~ . F . 1 data now show that cement setting c;m occur when the ratio is as low as 0.33 or lower. r~ the 3s presence of excess DCPA does not lead to residual DCPA in the end product;
.

woss/20368 2 ~ ~ t ~ ~;q .~ aloog the product is apatitic, probably a calcium deficient apatite that has poor crystallinity and greater solubility. Such material may have different in vivo from ihat of ~ h.~uA~I,u~it~ produced by calcium phosphate cement with a ITCP/DCPA ratio of 1.0, perhaps resorbing more s rapidly im bone.
The bone lGr- material, whether the preferred cement of S.N.
08/030,709 described - ~J above or otherwise, may contain a variety of additives and beneficial agents, provided they do not interfere with its setting arld bone r~ ' properties to arly substantial degree. Examples of such 10 additives amd agem's include handling agents (e.g., viscosity modifiers), extenders, crystal habit modifiers, biologically active substances, fillers and porosity agents.
The bone lGr' material may be supplied to the user in a variety of forms, includirlg as powders or as a powder miAture which is later mixed 15 with the liquid diluent to make putty; or as a pre-mixed putty which may contain a ~ extender, e.g., glycerin and/or propylene glycol. It may be supplied with or in the which is used to introduce the cement into the body, for example, a syringe, l device, "gun", calmula, 1.~ Ir packet, dentula, reamer, file, or other forms which will 20 be apparent to those of ordinary skiD im the art. The bone .Gl-l -- . - - - ' material is generaDy provided or employed in a sterili7ed condition. S .;1;,-1;..,. may be ~ , e.g., ~or the preferred cement by gamma-ray radiation, typically at a dose of 2.5 Mrad.
The inventive apparatus and methods have been compared with various 2s alternative approaches to the repair of bone defects, especiaDy burr holes. In one type of attempted repair, a resorbable foam ("GELFOAM") was used as a floor for the cement within crani~l holes 14 '- in diameter and 1.5 to 2.0 deep. The method was r'- 1, as the "GELFOAM"
was not entirely stable and becan~e weak very quickly when wet. Repairs were wo ss/2036s 2 1 8 ~ 1 39 PCT/US95/01009 also attempted (1) with a lattice of bone g~afts i~nd plates covered with cements, or (2) with bone ~ cement located ~ , and the scaffolding located distially im the repair. None of these techniques compared favorably with the inventive technique and apparatus.
s It should be ~ ' ~ that the foregoing disclosure, . ' certain specific i ' " of the invention and that all, ~ A ~ or ;~
equivalent thereto are within the spirit or scope of the imvention as set forth in the appended claims.

Claims

WHAT IS CLAIMED IS:

1. An apparatus comprising a scaffolding to support a bone replacement material for the repair of a craniomaxillofacial bone defect in which a portion of the bone is missing wherein the scaffolding is biocompatible and comprises an insert segment which is thinner than a depth of the bone defect, the insert segment having a contour and a perimeter which respectively approximate a contour and a perimeter of a proximal surface of the missing portion of the bone;
and wherein the scaffolding further comprises means, adapted to be disposed on adistal surface of hte bone at an edge of the defect, for supporting the insert segment at a proximal surface of the bone defect.

2. The apparatus of claim 1 wherein the craniomaxillofacial bone defect to be repaired is a full-thickness craniomaxillofacial skeletal defect.

3. The apparatus of claim 1 wherein the bone defect to be repaired is selected from the group consisting of burr holes, orbital floor defects, orbital rim defects, mastoid defects, maxillary defects and cranioplasty.

4. The apparatus of claim 3 wherein the defect to be repaired is a burr hole.

5. The apparatus of claim 1 wherein the scaffolding is comprised of a material selected from the group consisting of a metal and a metal alloy.

6. The apparatus of claim 1 wherein the scaffolding is comprised of a material selected from the group consisting of an osseointegrative metal and ametal alloy containing an osseointegrative metal.

7. The apparatus of claim 1 wherein the scaffolding is comprised of a substance selected from the group consisting of titanium, titanium-aluminum alloy, vitalium, stainless steel, cobalt-molybdenum alloy, calcium phosphate silicate and aluminum oxide.

8. The apparatus of claim 7 wherein the scaffolding is comprised of titanium.

9. The apparatus of claim 1 wherein the scaffolding is formed from a unitary piece of titanium micromesh.

10. A composite comprising the apparatus of claim 1 wherein the craniomaxillofacial bone defect has side walls, the apparatus being overlaid with a bone replacement material contoured to fill a space bounded by the side walls of the craniomaxillofacial bone defect, the insert segment of the scaffolding and the distal surface of the bone defect.

11. The composite of claim 10 wherein the bone replacement material is selected from the group consisting of calcium phosphate based materials, silicate acrylic salts, sintered hydroxyapatite granules, replaminform hydroxyapatite, corraline hydroxyapatite, apatite granules and biocompatible osseoconductive polymers.

12. The composite of claim 11 wherein the bone replacement material is a calcium phosphate based material.

13. The composite of claim 12 wherein the calcium phosphate based material is a low temperature-hardening gradually resorbable hydroxyapatite forming cement.

14. A surgical method for the repair of a craniomaxillofacial bone defect in which a portion of the bone is missing comprising inserting the apparatus of claim 1 into the defect so that the insert segment is flush with the proximal surface of the bone defect; providing means for stabilizing the scaffolding to the surrounding bone; stabilizing the scaffolding with stabilizing means; filling the bone defect with bone replacement material and contouring the material.

15. The surgical method of claim 14 further comprising adapting the apparatus of claim 1 to fit the bone defect by trimming the scaffolding.

16. The surgical method of claim 15 further comprising bending the means for supporting the insert segment to adapt it to the conformation of the defect and surrounding bone.

17. The surgical method of claim 14 further comprising inserting an orthopedic screw in the means for supporting the insert segment and into the surrounding bone.

18. The surgical method of claim 14 wherein the craniomaxillofacial bone defect to be repaired is a full-thickness craniomaxillofacial skeletal defect.

19. The surgical method of claim 14 wherein the bone defect to be repaired is selected from the group consisting of burr holes, orbital floor defects, orbital rim defects, mastoid defects, maxillary defects, and cranioplasty.

20. The surgical method of claim 19 wherein the defect to be repaired is a burr hole.

21. The surgical method of claim 14 wherein the scaffolding is comprised of a material selected from the group consisting of a metal and a metal alloy.

22. The surgical method of claim 14 wherein the scaffolding is comprised of a substance selected from the group consisting of titanium, titanium-aluminum alloy, vitallium, stainless steel, cobalt-molybdenum alloy, calcium phosphate silicate, and aluminum oxide.

23. The surgical method of claim 14 wherein the scaffolding is comprised of titanium micromesh.

24. The surgical method of claim 14 wherein the bone replacement material is selected from the group consisting of calcium phosphate base materials, silicate acrylic salts, sintered hydroxyapatite granules, replaminform hydroxyapatite, corraline hydroxyapatite, apatite granules, and a biocompatible osseoconductive polymers.

25. The surgical method of claim 24 wherein the bone replacement material is a low temperature-hardening gradually resorbable hydroxyapatite forming cement.

26. An apparatus comprising a scaffolding to support a bone replacement material for the repair of craniomaxillofacial bone defects wherein the scaffolding is biocompatible and comprises an insert segment, a stabilization segment and a connecting segment, wherein the insert segment is comprised of a material selected from the group consisting of a biocompatible metal and a biocompatible metal alloy, and is thinner than a depth of the defect, the insertsegment having a contour and a perimeter which respectively approximate a contour and a perimeter of a proximal surface of a missing portion of the bone; the stabilization segment is thinner than the depth of the defect and is adapted to be disposed on a distal surface of the bone at an edge of the defect; and the connecting segment rigidly connects the insert segment to the stabilization segment.

27. The apparatus of claim 26 further comprising an opening in the stabilization segment adapted to receive a threaded portion of an orthopedic screw having a screw head, but to prevent passage of the screw head, and an orthopedicscrew sized to cooperate with the stabilization segment.

28. The apparatus of claim 26 wherein the craniomaxillofacial bone defect to be repaired is a full-thickness craniomaxillofacial skeletal defect.

29. The apparatus of claim 26 wherein the bone defect to be repaired is selected from the group consisting of burr holes, orbital floor defects, orbital rim defects, mastoid defects, maxillary defects and cranioplasty.

30. The apparatus of claim 26 wherein the defect to be repaired is a burr hole.

31. The apparatus of claim 26 wherein the scaffolding is comprised of a material selected from the group consisting of a metal and a metal alloy.

32. The apparatus of claim 26 wherein the scaffolding is comprised of a material selected from the group consisting of an osseointegrative metal and ametal alloy containing an osseointegrative metal.

33. The apparatus of claim 26 wherein the scaffolding is comprised of a substance selected from the group consisting of titanium, titanium-aluminum alloy, vitallium, stainless steel, cobalt-molybdenum alloy, calcium phosphate silicate and aluminum oxide.

34. The apparatus of claim 33 wherein the scaffolding is comprised of titanium.

35. The apparatus of claim 26 wherein the scaffolding is formed from a unitary piece of titanium micromesh.

36. A composite comprising the apparatus of claim 26, wherein the craniomaxillofacial bone defect has side wails, the apparatus being overlaid with a bone replacement material contoured to fill a space bounded by the side walls ofthe craniomaxillofacial bone defect, the insert segment of the scaffolding and the distal surface of the bone defect.

37. The composite of claim 36 wherein the bone replacement material is selected from the group consisting of calcium phosphate based materials, silicate acrylic salts, sintered hydroxyapatite granules, replaminform hydroxyapatite, corraline hydroxyapatite, apatite granules and biocompatible osseoconductive polymers.

38. The composite of claim 36 wherein the bone replacement material is a calcium phosphate based material.

39. The composite of claim 38 wherein the calcium phosphate material is a low temperature-hardening gradually resorbable hydroxyapatite forming cement.

40. A kit for the repair of craniomaxillofacial bone defects comprising an apparatus as in claim 1 and a bone replacement material, packaged together.

41. A kit as in claim 40 wherein the bone replacement material comprises precursors capable of being combined to form a low temperature-hardening gradually resorbable hydroxyapatite forming cement.

42. A kit for the repair of craniomaxillofacial bone defects comprising an apparatus as in claim 26 and a bone replacement material packaged together.

43. A kit as in claim 42 wherein the bone replacement material is a low temperature-hardening gradually resorbable hydroxyapatite forming cement or precursors therefor.