Biodegradable

Bioresorbable
IPRO5
 Background – Artroscopia
 Utilizarea implantelor biodegradabile este in crestere in
medicina sportiva si traumatologie
 Varietate mare: suruburi de interferenta, capse, suturi,
ancore, pin-uri (brose)
 Background – Reconstructia
ligamentara
 90,000 reconstructii anuale in lume

 grefe din tendon patelar sau semitendinos

 implantate in femur si tibia

 multiple tehnici de osteosinteza

 Background –Reconstructia
ligamentara
 Lambert = fixarea interferenta « golden
standard »
 Lambert K. Vascularized patellar tendon graft with rigid internal fixation for
anterior cruciate ligament insufficiency. Clin Orthop 1983;172:85-89.
 Background – Suruburi
 Titan:
 rezistenta
 biocompatibil
 sigure
 A doua interventie pentru
ablatia materialului

 Biodegradabile:
 Rezistenta dependenta de
dorma
 Multipli polimeri:
 Poly(L-Lactic) Acid (PLLA)

 Poly(Lactic-co-Glycolic)

Acid (PLGA)
Background – Suruburi
 Dezavantaje suruburi metalice :
 Lezarea grefei
 Ablatia dificila
 RMN artefacte
 Kousa P, Jarvinen TL, Pohjonen T, et al.
Fixation strength of a biodegradable
screw in anterior ligament reconstruction.
J Bone Joint Surg Br 1995;77:901-905.
 Clinica - Optiuni
 Analiza literaturii / implante biodegradable =
la 400 N tensiune (~ recuperare/sport) =
aceeasi rezistenta la smulgere
 Holden JP, Grood ES, Korvick DL, et al. In vivo forces in
the anterior cruciate ligament: Direct measurements during
walking and trotting in a quadruped. J Biomech
1994;27:517-526.
 Morrison JB. Function of the knee joint various
activities.Biomed Eng 1969;4:573-580.
 Markolf KL, Burchfield DM, Shapiro MM. Biomechanical
consequences of replacement of the anterior cruciate
ligament with a patellar ligament allograft. Part II: Forces in
the graft compared with forces in the intact ligament. J
Bone Joint Surg Am 1997;78:1728-1734.
 Noyes FR, Butler DL, Grood ES, et al. Biomechanical
analysis of human ligament grafts used in knee-ligament
repairs and reconstructions. J Bone Joint Surg Am
1984;66:344-350
Clinica - Observatii
 Dezavantajul suruburilor IF
de a fi in contact cu lichidul
articular = reactii sinoviale
 Weiler A, Hoffmann RF, Staehlin
AC, et al. Biodegradable implants
in sports medicine: The biological
base. Arthroscopy 2000;16:305-
321.
Clinica - Observatii

 Alt dezavantaj IF – implantare

dificila in pozitia posterioara
(necesara izometriei) – risc
efractie cortex posterior
Cross Pin
 Tehnici
alternative de
fixare
 Clinica - Discutii

= Stabilitate comparativa a
celor doua tehnici de
fixare
 Diferente privind modul
de esec:
Weimann A et al. Primary
Stability of Bone–Patellar  fractura = CP
Tendon Bone Graft Fixation
With Biodegradable Pins  pull-out (smulgere) = IF
Arthroscopy: The Journal of
Arthroscopic and Related
Surgery, Vol 19, No 10
(December), 2003: pp 1097-
1102
Clinica - Discutii
 Complicatii -1 articol
 Ilkyu Han, Yeon Ho Kim,
Jae Ho Yoo, Sang Cheol
Seong,Tae Kyun Kim -
Broken bioabsorbable
femoral cross-pin after
anterior cruciate ligament
reconstruction with
hamstring tendon graft a
case report Am J Sports
Med, 2005 Vol. 33, No.
11
Problema - Motivatie

 = Probleme!
 Design actual implante poate produce
debris-uri
 Materiale actuale implante nu
promoveaza cresterea tisulara

 Loc pentru noi modele/design!

 Design
Implantul biodegradabil ideal:

 rezistenta in timp
 bioabsorbtie – cu mentinere rezistenta
 biodegradare in timp util
 fara produsi locali care afecteaza functia osoasa
 materiale sigure
 toxicitate, antigenicitate, pyrogenicitate, or
carcinogenicitate;
 usor de sterilizat
 capabile de constrangerile tehnicii chirurgicale
Materiale
 Poly(Lactic-co-Glycolic) Acid (PLGA):
 Degradable in vivo
PLGA
 Alginate Hydrogel:
 Posibil de suplimentat cu nutrienti, metaboliti etc.
 Structura 3D ce promoveaza functia celulara
Design Materiale ~ 40 !
 Polyglycolide (PGA) si copolimeri: polyglycolide-co-
trimethylene carbonate (PGA-co-TMC), poly-(D,L-lactide-co
glycolide) (PDLLA-co-PGA), poly-(L-lactide-co-glycolide)
(PLLA-co-PGA).
 Poly-(L-lactide) (PLLA), poly-(D,L-lactide) (PDLLA), si
stereocopolimeri (L si D,L parts).
 Polydioxanone (PDS)
 Trimethylene carbonate (TMC)
 Polyorthoester (POE)
 Poly-c-capralacton (PCL)

 Materiale composite
 PLLA/tricalcium phosphate s
 PLLA/hydroxyapatite
Intrebare…
 Efectele acestor
substante pe
termen lung in
organismul
uman…
Degradare In Vivo
 Fragmente surub de interferenta PLLA la 20
luni de la implantare.
Literatura – procesul :
In Vivo Degradation
 1. Healing phase
 2. Latency phase
 3. Protracted resorptive phase
 4. Progressive resorptive phase
 5. Recovery phase
Degradare In Vivo
 12 luni de la implantarea unor
brose PGA, Weiler si
colaboratorii nu au gasit
material birefringent in zona de
implantare
 dar fragmente cristaline PGA
gasite in ganglionii aferenti si la
24 luni
Inlocuirea Osoasa
 3 modalitati:
 Crestere osoasa progresiva pe masura
degradarii implant
 Crestere osoasa in centrul zonei dupa ce
implantul s-a degradat
 Cicatrice osoasa in zona de implantare cu
dezvoltare marginala lenta de os nou
 Inlocuirea Osoasa
 Crestere osoasa
progresiva – cea mai
dorita dar rar intalnita.
Observata doar in
cursul degradarii
PLLA-co-PDLLA
(compozite)
Inlocuirea Osoasa
 Crestere osoasa
centrala –
fluorescenta
tetraciclinei ca
marker dupa
absorbtia pinurilor
Inlocuirea Osoasa
 Aspect CT-scan
scleroza osoasa
la locul
implantarii18 luni
dupa suruburi
PLLA-co-PDLLA
Inlocuirea Osoasa
 Formare osoasa lenta (18 luni) la marginea
zonei; tetraciclina fluorescenta
Inlocuirea Osoasa
 CT-scan la 30 luni dupa implant PLLA-co-
PDLLA.
 Refacere osoasa aproape completa
Fantome
 Fara aspect trabecular
 Fibroza calcificata partial

 Volumul zonei calcificate

 Mic in comparatie cu al
implantului initial (resorbtie
incompleta)
Fantome
 Nu exista studii
anatomopatologice
privind resorbtia
completa a implant
PLLA
Osteoliza
 Cavitati de
resorbtie cu aspect
chistic
Osteoliza
 Histologia:
 leucocite
 celule gigante cu
aspect de reactie
la corp strain
Osteoliza
 asociate cu implante tip PGA cu degradare
rapida.
 acumulare de fragmente de implant sau
produsi de degradare ce nu pot fi eliminati
adecvat de macrofage si leucocitele PMN
Ruptura
 risc de ruptura in cursul
implantarii
Experimental
 Pierdere 30% a capacitatii
maxime de rezistenta la 28 de
zile in vitro.
 Nu statistic semnificativ, iar
rezistenta ramanea de 500 N.
 Barber FA. Biology and clinical
experience of absorbable
materials in ACL fixation.
Technique Orthop 1999;14:34-
42.
Design?  factors ce contribuie la
biocompatibilitate:

O.D.  Forma implant

I.D.  Matlaga BF, Yasenchak LP,
Salthouse TN. Tissue
response to implanted
polymers: The significance of
sample shape. J Biomed Mater
Res 1976;10:391-397.
 Lam KH, Schakenraad JM,
Esselbrugge H, Dijkstra PJ,
Feijen J, Nieuwenhuis P.
Quantitative biocompatibility of
biodegradable polymers as
studied by physico-chemical
and cell biological parameters.
Pitch In: Doherty PJ, ed. Biomaterial
—Tissue interfaces.
Amsterdam: Elsevier, 1992;43-
48.
Classificarea Hoffman
 Osteolysis Radiological Findings
 O-0 None No osteolytic changes visible
 O-1 Mild Osteolytic changes at the implant site (osteolysis 1 mm or larger than implant diameter)
 O-2 Moderate Cystic-like extended osteolysis (osteolysis 3 mm or larger than implant diameter,
 O-3 Severe Confluence of osteolysis into a resorption cavity (if more than 1 implant is used)
 O-4 Disturbed healing Fracture displacement, fragment sequestration, or healing failure of soft tissue due to osteolysis

 Extra-articular Soft-Tissue Reactions Symptoms/Findings/Treatment

 EA-0 None No or subclinical reaction
 EA-1 Mild Local, mild soft-tissue induration; no treatment
 EA-2 Moderate Fluctuant swelling, fluid accumulation (ultrasound), local warmth swelling, pain; single or repetitive
puncture necessary
 EA-3 Severe Spontaneous discharge of sinus, primary sterile, secondary possible bacterial contamination;
debridement and open wound treatment
 EA-4 Bacterial superinfection Deep soft-tissue/bone infection following EA-2 or EA-3; extensive and repetitive debridement

 Synovial Reactions Symptoms/Findings/Treatment

 IA-0 None No or subclinical reaction
 IA-1 Mild Mild (sterile) joint effusion, no additional local or systemic signs of inflammation, single need for
puncture, foreign-body giant cells, round cells, or implant remnants in puncture fluid or synovial membrane
 IA-2 Moderate Significant (sterile) joint effusion, no other additional local or systemic signs of inflammation, need for
recurrent puncture, foreign-body giant cells, round cells, or implant remnants in puncture fluid or synovial membrane;
administration of nonsteroidal anti-inflammatory drugs, partial weight-bearing until disappearance of symptoms
 IA-3 Severe Significant (sterile) joint effusion with local signs of inflammation (pain, reddening, warmth), need for
recurrent punction or surgical revision (e.g., arthroscopic synovectomy), foreign-body giant cells, round cells, or implant remnants
in puncture fluid or synovial membrane
 IA-4 Bacterial superinfection IA-1 to IA-3 and positive microbiological examination, arthroscopic or open debridement with lavage
and synovectomy

 Hoffmann R, Weiler A, Helling HJ. Ktek C, Rehm KE.

Local foreign-body reactions to biodegradable implants. A
classification]. Unfallchirg 1997;100:658-666
Experimental - SEM of PLA screw
 Imagini Prof Dr Ing Florin Miculescu - UPB
SEM of PLA screw
 Analysis of implant failures by SEM
suggested that
 the amount of threads engaging the bone plug
differed in the screw and wedge designs.
SEM of PLA screw
in vivo degradation
progressive cracking and breakdown
 SEM / PLA
 progressive
increase in cracks
and cavitation on
the root and
thread with time
 SEM / PLA
 significant
thread damage
attributable to
bone plug
pullout.
 Future Work – Biomaterials
 Test mechanical properties
on bovine/human bone
 Insertion torque
 Pullout strength
 Test adhesive strength of
materials
 Mold development
 Rapid Prototyping: Casting
of mold/ Machining
 PLGA degradation
testing/research
 Tissue growth assays
 Future Work - Design
 Optimizing screw shape
 Screw thread dimensions
 Minimize shear on graft
 Maximize pull out strength in vivo
 Driver shaft dimensions
 Maximize torque and shaft/screw
interface
 Finite Element Analysis
 Thread(PLGA)—Tissue Interface
 PLGA—Alginate Interface
 Driver—Alginate Interface
Conclusion
 Furthermore, in
vivo long-term
studies are
necessary, with
follow-up until
implant remnants
have disappeared
and an osseous
replacement has
taken place.