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     Investigating the Influence of Architecture and Material Composition of 3D Printed Anatomical Design Scaffolds for Large Bone Defects
           but this approach requires a complex surgical procedure   jetting allowing high reproducibility and precise control
           usually performed in specialized clinical centers [7]-[10] .  over the porosity, PS, and pore interconnectivity [22]-[26] .
             Bone  shortening  allows  bone  healing  to  start   Under an Engineering and Physical Sciences Research
           immediately and assists soft tissue coverage by reducing   Council/Global  Challenges  Research  Fund  (EPSRC/
           the defect size or soft tissue tension . However, for very   GCRF) project entitled “Bone Bricks: Low cost-effective
                                        [11]
           large bone defects (>8 cm), this clinical approach must be   modular  osseointegration  prosthetics  for  large  bone
           combined with other treatments to be effective .    loss  surgical  procedures”  authors  aim  to  develop  and
                                                  [11]
             Distraction osteogenesis is based on the principle that   implement  a  novel  low  cost  osseointegrated  modular
           bone and soft tissues can be regenerated under tension. It   prosthetic  solution  to  treat  large  bone  loss  injuries  to
           involves the application of a modular-ring external fixator   enable  limb  salvage.  The  immediate  application  is  to
           and allows early bearing, stimulates local blood flow, and   treat Syrian refugees who have been displaced to Turkey.
           produces good quality bone. However, it is a complex and   The project proposes to build on the current treatment of
           laborious technique usually associated with chronic pain,   external fixation but with the addition of an engineered
           infection, nervous, and vascular injury and scars due to the   internal prosthetic implant to improve patient outcomes,
           metal wires transfixing and cutting through soft tissues .  avoid  painful  limb  lengthening,  and  reduce  recovery
                                                        [12]
             Masquelet  and  Begue ,  proposed  a  two-stage   time. A  patient-specific  prosthetic  to  fill  the  bone  lost
                                  [13]
           approach  to  treat  bone  defects  in  both  septic  and   due  to  injury  is  being  developed  using  biodegradable
           aseptic  conditions.  First,  a  cement  spacer  is  placed  in   and biocompatible modular pieces (bone bricks), from a
           the bone defect, inducing the formation of a biological   pallet of shapes and sizes that fit together in a Lego-like
           membrane  around  it [14],[15] .  Then,  the  cement  spacer  is   way  to  form  the  prosthesis.  The  assembled  prosthesis
           removed, and a biological graft is placed within the tube   will  create  a  hollow  cage  which  will  be  filled  with  an
           of  the  induced  impermeable,  vascular,  and  biological   infection  prevention  paste  containing  calcium  sulfate
           active  membrane [14],[15] .  However,  autografts  despite   and  polymeric  microbeads  encapsulating  antibiotics
           being  osteogenic,  osteoinductive,  and  osteoconductive   (Figure  1).  This  paper  presents  preliminary  results
           and  have  no  risks  of  immunogenicity  and  disease   considering  anatomical  designed  bone  bricks  produced
           transmission,  present  several  limitations  such  as  pain   using  different  architectures  and  material  composition.
           and  morbidity  in  the  donor  site,  limited  quantity  and   Produced  structures  are  morphologically,  mechanically,
           availability, prolonged hospitalization time, the need for   and biologically investigated.
           general sedation or anesthesia, risk of deep infection and
           hematoma, extended non-weight bearing, and the risk of   2. Materials and methods
           inadequate graft hypertrophy [16]-[19] .
             Moreover,  current  clinical  approaches  require   2.1. Materials
           long  inability  periods  with  consequences  difficult  to
           quantify  (social  integration,  family,  and  psychological/  Polycaprolactone (PCL) (CAPA 6500, Mw = 50000Da), a
           mental  problems).  They  are  also  expensive,  and  some   semi-crystalline linear aliphatic biopolymer, was supplied
           are  relatively  complex,  posing  significant  problems  to
           surgeons  treating  groups  of  risk  such  as  refugees  and
           victims of conflict zones . Therefore, there is a demand
                               [20]
           for  novel  bone  replacements,  which  must  be  cost-
           effective,  biocompatible,  infection  resistant,  bespoke,
           or modular, providing the initial bone stability to allow
           weight-bearing and biological integration for long-term
           stability .
                 [21]
             A  range  of  different  techniques  has  been  explored
           to  produce  physical  supports  for  cell  attachment,
           proliferation,  and  differentiation.  These  techniques
           include conventional processes such as solvent casting,
           freeze-drying,  phase  separation,  gas  foaming,  melt
           molding, and particle-leaching, usually involving the use
           of toxic organic solvents and not allowing the control of
           porosity,  pore  size  (PS),  pore  shape,  pore  distribution,
           and  pore  interconnectivity;  and  additive  manufacturing
           processes  such  as  vat-photopolymerization,  extrusion-
           based processes, powder-bed fusion, binder, and material   Figure 1. Bone bricks approach for large bone loss treatment.
           44                          International Journal of Bioprinting (2021)–Volume 7, Issue 2
     	
