Presentation on theme: "Update on Biologics in Orthopedic Sportsmedicine Cells and Growth Factors William F Bennett MD."— Presentation transcript:
1Update on Biologics in Orthopedic Sportsmedicine Cells and Growth Factors William F Bennett MD
2Injured Tissue-The Basics of Healing Requires Cells and Growth Factors Tissue repair relies on vascularity and cellular migrationBlood escapes, hematomaPlatelets, pluripotential stem cells form scaffold for neocellular proliferationCells respond to Growth Factors(Bioactive agents)Some cells respond different to growth factors based upon tissue
3Growth Factors/Bioactive Agents At the time of injury released, Gfs bind to receptors and effect cellular function.Part of inflammatory response.ProteinsAnabolic/catabolicCytokines-extracellular proteinsEffect cell to cell mediationExamples- Interferon/interleukin/tumor necrosis factor
4Growth Factors Transforming Growth factor-beta(TGFB)-Largest group Over 100 membersAnabolic effect on all components ofMusculoskeletal tissue
5Common Types of TGF-Beta Bone Morphogenic proteins-BMP’sOsteoprogenitor derived cells-promote bone growthPlatelet Derived Growth Factor-PDGFFrom platelets and stimulates angiogenesis, chemotactic influence and mitogenicInsulinlike Growth Factor-IGF-1From variable cells, broad anabolic effectFibroblast Growth factor-bFGFEarly differentiation of cells and tissue and in repair process
6Common Types of TGF-Beta cont’d Epidermal Derived Growth Factor-EGFProliferates ectoderm and mesodermGrowth and differentiation Factor-GDF-5Chondrocyte, fibroblast and mesenchymal cell expansion
7Bone Healing Two clinically available BMP’s-stimulates bone growth rhBMP2-Recombinant BMP- (Infuse, Medtronic Sofamor Danek, Minneapolis, Mn.)BMP 7-(osteogenic protein-1- OP1)Stryker, Biotech, Hopkinton, Ma,LMP1-Lyophilized Mineral proteinStimulates BMPPDGF and Platelet Rich Plasma may interfere with bone healingBMPs help reduce non-union rate, spinal fusion rate and possibly open wedge osteotomy non-healing
8Bone To Tendon HealingBMP2 and OP1 have been shown to aid in the tendon to bone healingAlthough the exact mechanism for this repair process is not well known
9Tendon To Tendon Mechanism not well defined GDF5 may play a role IGF1 and PDGF2Increased collagen synthesisThese factors can be found in augmentation tissues like porcine submucosa, bovine, equine collagen and human allograft dermisCascade- shows to repair tissue- platelet rich plasma !!!!!!!!!!!!!!!
10Ligament Healing Cell Proliferation, Type 1 Collagen and proteoglycan synthesis are stimulated by bFDF, PDGF and bTGFMethod of delivery will be a gene-enhanced delivery system via fibroblast cells transduced by plasmid or virus carrying these growth factors
11Meniscus HealingMeniscal tears heal better when ACL reconstruction is done at the same time.Suggests that something in the blood augments healingArnozcky has shown a fibrin clot to help healing.Platelet Rich Fibrin Matrix(PRFM)Cascade- ultracentrifuge of bloodPlatelt rich ultracentrifugate is further centrifuged down to a volume-stable suturable fibrin matrix
12Articular Cartilage Healing is not regeneration Articular cartilage is Hyaline cartilageType 2 collagenHeals to injury with fibrocartilageType 1 collagenNo vascular supplyNo nervesMore of a scar tissue than normal tissue
13Articular Cartilage Repair Fissuring- chondroplasty, smooths edges only, no healingOsteochondral defects- microfracture technique or marrow stimulation techniques-forms fibrocartilageCartilage-growth factorsBmp2/1IGF/bTGFAdd these to cell colonies, like genzyme cell cultures- get better hyaline cartilage
14Cartilage Systems-U.S. Lavage and debridement Chondroplasty MicrofractureOatsPolymer bone plugsOsteochondral allograftsCartilage cultures- Genzyme onlyCambridge Ma
15Cartilage CulturesCarticel- Genzyme-using chondrocytes, cartilage cells as opposed to stem cells.Bx, 4-6 weeks later can replant with cultured cells, use periosteal patch, open surgery, collagen membrane 2nd generation……using presently.Next gen Carticel, MACI-matrix impregnated with cells, no periosteal patch
16Other source of Cells than chondrocytes Stem Cells Both an evolution and a revolution in modern biomedicine.Concept is rather than introduce organ transplant, one would implant certain population of cells to allow regenerationBone marrow transplantation is intermediate between organ and stem cell transplant.
17Present ApplicationsBone Marrow transplant- for radiation loss of blood cells and their progenitor lines.Stem cell skin grafts for burn victims.Corneal stem cell implants.Pancreatic islet cell implantation.
18Applications in genetically defective cell lines Genetically corrected stem cells used to treat;Muscular dystrophyOther disease processesFuture will be in musculoskeletal areas as well.
19Stem Cell Types Myth and Fact Adult stem cells identified from brain to muscle.Fetal Stem cells- aborted fetuses or umbilical chordEmbryonic stem cells-Discarded from in vitro fertilizationSomatic Nuclear Transfer- a nucleus from a normal body cell is placed into a fertilized egg with its nucleus removed.The fertilized egg has the effect of “resetting” the nucleus to a primordial state.No ethical considerations with fetuses here!
20Embryonic versus Adult Ubiquitous component of the embryo.Defined by position in the embryoDivide in culture without changing charcteristics.Single cell can give rise to a colony of cells.Adult--rare, difficult to identify, unknown origin, partially understood function and life history-defined by complex list of features.-can not divide indefinitely.
21Stem CellsMaintain undifferentiated phenotype until exposed to appropriate signals.With signals can differentiate into specialized cells that have structure and functionMesenchymal Stem cells are of this type-MScs- bone marrow.Mesenchymal is from a layer in the developing embryo.
22What we know and do not know Know some signalsDon’t know all intermediate stepsDon’t know how exactly how one cell changes to another.Don’t understand the microenvironment completely.Adult and MSC have limited differentiation potential compared to embryonic stem cells and limited number of replication cycles.
23Stem Cell Exhaustion Stem cells may be exhausted Has been shown to happen in degenerative conditions, especially osteoarthritis.
24FutureOver next 5-10 years there will be major commercial development in the area of stem cell enterprises.