What is the source of an Integra graft

Use of integra to achieve a neodermis

Studies evaluating the use of Integra have demonstrated both positive and negative features of the product. One study compared Integra to routinely used skin replacement materials including autograft, allograft, xenograft or a synthetic dressing. It was found that patients treated with Integra required significantly thinner epidermal grafts, their donor sites healed faster and there was less hypertrophic scarring at the recipient site.

Another trial compared Integra to Biobrane and allograft in comparable patients and favored the latter as all of the Integra covered sites became infected.

The longest retrospective review of Integra, over a 10-year period, revealed a take of over 80%, 93% had absent or minimal hypertrophic scars at the recipient site, 100% good to excellent function of any involved joints. Furthermore, over 70% of patients at 6 months post op reported that the Integra dermal regenerative template felt more like normal skin and more comfortable compared to autografts.

16.3.7 Cadence total ankle system

The Cadence (Integra Lifesciences, Plainsboro, NJ), introduced in 2017, is a fixed-bearing implant developed to maintain anatomic kinematics. The system is made of a cobalt-chrome alloy with a porous titanium plasma spray coating. The tibial component has two 45-degree angled pegs and a posterior fin for fixation which is not prepped prior to insertion, allowing for a solid press fit. The tibial component has a fibular cutout to maximise coverage along three cortices, reducing fibular impingement and necessitating left and right options. The talar component requires minimal bone resection and utilises two pegs for fixation. The talar component articulation is based on an 8-degree conical axis in efforts to replicate the natural kinematics of the ankle and has a sulcus design for rotational stability.

The polyethylene insert is ultrahigh molecular weight polyethylene. The inserts can be anterior or posterior biased, helping to reduce the talus under the tibial axis in cases of anterior or posterior subluxation.

There are no published data series regarding the Cadence system.

19.3.1.4 Interposition – Partial trapezial resection – Constrained

The PyroDisk (Integra Life Sciences, Austin, TX, United States) PyC nonanatomic interposition implant was designed by Hamlin. It is a biconcave disk with a central hole to allow stabilisation with a tendon, usually FCR or APL, designed to be implanted with a partial trapeziectomy. Early experience in Europe was encouraging, with excellent outcomes with regard to pain and functional scores (Barrera-Ochoa et al., 2014; Cuenca-Llavall, Lizano-Díez, Cruz-Sánchez, Cebamanos-Celma, & Pidemunt-Moli, 2018; Mariconda, Russo, Smeraglia, & Busco, 2014; Odella, Querenghi, Sartore, Felice, & Dacatra, 2015; Oh et al., 2019). The implant is easily revised to a trapeziectomy and early revisions for pain were found in 10%–38% of patients (Barrera-Ochoa et al., 2014; Cuenca-Llavall et al., 2018; Mariconda et al., 2014) on midterm follow-up. Smeraglia et al. have recently reported on 46 partial trapeziectomies and PyroDisk interpositions with an average of 9.5 years follow-up; 7% (3/46) of patients were revised to a trapeziectomy, all within the first 2 years. Unrevised patients had sustained and significant improvements in DASH, VAS, Kapanji and key pinch strength (Smeraglia et al., 2020). Although these results are promising, it remains unclear if these results are superior to more common techniques such as trapeziectomy and tendon interposition. Bellemere reported on a series of 80 cases. He found the revision rate for chronic pain was 6% (Bellemère, 2019). He felt that the tendon graft increases the constraint of the prosthesis with resultant increases in peak stress that may explain the increased pain.

14.6 Vascularised bone transfers

If one desires a bone reconstruction ad integrum, it is necessary to resort to a vascularised bone transfer. Indeed, only the transfer of a bone with its own vascular network enables reliable correction of hypocellularity, hypovascularisa- tion and hypoxia at the same time. Given local conditions, muscular and skin tissue will be transferred with the graft. Parameters affecting the choice of flap used include:

the mandibular or maxillar portion to reconstruct;

the length of bone to reconstruct;

soft tissues and necessary skin;

vascular state of the patient, arteriopathy;

side-effects concerning the harvest;

the possibility of working in a double team (one team performing the harvest simultaneously with the other team preparing the graft site) without need of position change;

training and customs of the surgical team;

projection of implant rehabilitation.

In any case, an arterial assessment of the neck vessels (doppler exploration of supra-aortic trunks, arteriography or angiotomography) may be useful, as the receiving vessels of the flap may accumulate radic or arteriopathic lesions. According to some authors,18 the complication rate of free flaps does not differ whether the patient has been irradiated (with or without osteoradionecrosis) or not.

The dissection of the receiving vessels and the vascular anastomosis with the irradiated vessels are sometimes delicate, increasing the risk of thrombosis.

The patient has to be informed of the risks of the surgery, notably of the therapeutic dead end in which he may find himself in the case of failure, as well as the risk of a massive haemorrhage in case of anastomosis rupture.

The transfer of non-irradiated bone with its own vascular network in an irradiated region enables, in addition to the supply of bone, a revascularisation of the surrounding tissue which ensures a better healing and bone consolidation: this is termed ‘revascularisation’ surgery, which provides local capacities for angiogenesis and bone induction. The healing of the flap is independent of changes in local conditions. A neovascularisation develops in contact with the flap, even in irradiated situations.9

This type of flap is also of interest because it provides in a single step both the bone and the soft tissue necessary for reconstruction. The overall costs of such care-taking, in terms of the duration of hospitalisation, is less than it is with successive steps.

The success rate of the free flaps in irradiated terrain is 90% for the majority of teams. Radiotherapy does not seem to influence the rate of the local post-surgery complications, which vary from 9% to 85% depending on the population under study.18 However, it seems that, as for bone graft, a two-stage surgery gives better results and fewer complications.21

14.6.1 Fibula free flap

This is unquestionably the best flap for the great majority of authors. Indeed, it offers numerous advantages:20

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A large available length: 25 to 27  cm, which allows reconstruction of an entire mandible, if necessary.

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In its vascular pedicle the fibular artery is of good diameter (2 to 3  mm) and can measure up to 12 to 15  cm, if the distal portion of the fibula is used as well. This makes the micro-surgery easier, with a tension-free anastomosis, and makes a contralateral anastomosis possible if necessary, without resorting to a veinous graft. This pedicle length may be very useful for patients with a history of radiotherapy, atherosclerosis, or having undergone cervical lymphatic scraping with vascular ligature.

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The possibility of multiple osteotomies, thanks to a rich periostal vascularisation: a better morphological adaption of the flap to the bone substance loss to reconstruct may be achieved, provided that the periosteum is conserved (Fig. 14.4).

14.4. Mandibular arch reconstruction with two osteotomies and four osteosynthesis on a free fibula flap.

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The harvest is performed without a tourniquet. The duration of the harvest is not modified, blood loss is negligible if the hemostasis is done correctly, and there is no risk of a wound on the pedicle going unnoticed. Furthermore, this technique of harvest is better tolerated by weak patients, and the surgical consequences at the site of the harvest are very simple.

The flap is shaped (osteotomised and synthesised) on the donor site and the clamping of the pedicle is performed at the last moment, minimising the ischemia duration (Fig. 14.5).

14.5. Flap shaping on the donor site.

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The osteosynthesis is performed using miniplates, rather than reconstruction plates, as miniplates potentially improve bone consolidation through transmission of the mechanical forces to the bone. They do not endanger the flap vascularisation, as they respect the periosteum and allow a good modelling.

The thick reconstruction plates absorb the ensemble of the biomechanical forces. Therefore, they are to be avoided, because of their trend to exteriorisation (particularly in the symphyseal region), the risk of breaking, and the disturbance their screws can cause to the implants setup.

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The possibility to work in a double team: one team works at the head of the patient, performing the excision, and preparing the receiving vessels, whereas a second team harvests the flap. This allows shortening surgery duration for weak patients.

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The insertion of bone-integrated implants is nearly always possible on a fibula flap at the same time as the flap: indeed, the fibula measures on average 12  mm thick, rich in solid cortical bone. Setting up implants during an initial gesture allows reduction in the delay of dental rehabilitation and to reduce the number of interventions, but it can endanger the viability of the flap, as well as the viability of the osteosynthesis. Furthermore, the correct positioning of the implants during the first step is difficult and the time of surgery is prolonged, which is not always desirable with weak patients. This is why our experience makes us prefer to delay implants placement (3 to 6 months after the flap). The success rate of the implants are close to those obtained in native bone, with 98% success after one year and 93% survival of implants after 8 years22’23 (Fig. 14.6).

14.6. ((a), (b)) Implants and prothesis on a free fibula flap.

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The possibility of adding a skin palette, which is very interesting, since it is reliable, thin, malleable, easy to model for intra-oral reconstruction, and independent of the connection with the bone.

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Maxilla reconstruction is also possible with this technique.

The fibula free flap has few disadvantages:

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In the case of diabetes or arteriopathy of the lower limbs, an arteriogram of the vascular axes is necessary and the harvest of the fibular artery may be contra-indicated.

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The bony thickness of the transplanted fibula is sometimes insufficient to allow implants. This is most often the case with women, when the fibula measures less than 10  mm in thickness. This default may be removed by realising a ‘double-barrel’,24 which reduces the bone length necessary for the reconstruction (Fig. 14.7). Other techniques that are sometimes used for increasing the height of the bone, either in performing secondary bone grafts or a vertical osteogenic distraction of the transplant up to the desired height, are not recommended in irradiated terrain.

14.7. Double barrel free fibula flap.

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There are no sequelae regarding the function of the lower limbs and the morbidity rate on the donor site is low.25

14.3.1 Bone regeneration

The regeneration process reaches in its last stage a restitution ad integrum. In this case the defect is fully restored and contains a tissue that resemble the originally existing bone. In terms of biomaterials, bone regeneration is achieved in two scenarios. First, the use of nonresorbable osteosynthetic biomaterials to stabilize fracture that can heal by contact and reaches a full regeneration. After the removal of osteosynthetic materials, the impaired region is fully regenerated and do not contain any external biomaterial. Similar process takes place when resorbable osteosynthetic biomaterials that originally served for stabilization of the defect are fully degraded and the defect shows full regeneration. Second, the use of resorbable bone substitute materials to regenerate bone defect that possess a high regenerative capacity e.g., in a fracture gap or in a small jaw defect. In this case the resorbable biomaterial initially supports the regeneration process and allows new bone formation. After biomaterial degradation restitutio ad integrum is achieved the defect contains only newly formed bone (Fig. 14.5(a)).

16.8.1 Frame placement

Different stereotactic systems are available, such as Leksell (Elekta, Stockholm) and CRW (Integra Radionics, Burlington, MA). The frame can be placed under local anesthesia or sedation. The patient can be sitting or in the supine position and placement is well tolerated by most patients. When implanting DBS, our preference is to shave the entire scalp before frame placement. It is also possible to shave smaller areas according to a patient’s individual preference. The frame should be centered on the head and aligned with the canthal-meatal line, which is approximately parallel to the intercommissural line. Modern stereotactic planning software can compensate for most frame rotation. In patients with prior craniotomies or skull defects it may not be possible to place the frame symmetrically to avoid transcranial penetration of the pins. Images are acquired with the head frame and fiducial box and loaded into planning software stations for fiducial localization and co-registration.

Frameless systems are an alternative to frame-based stereotaxis. These are disposable mini-frames that are either custom-built for each patient or adjusted with optical neuronavigation. It is the tool of choice for many surgeons. Studies have shown no difference in lead positioning when frame-based or frameless implantations are compared (Burchiel, Mccartney, Lee, & Raslan, 2013; Henderson, 2004; Holloway et al., 2005).

19.5.3 CMC joint hemi-arthroplasty – non-anatomic

Trapezial arthroplasty using the Pyrohemisphere was published by the Mayo group in 2009 [61]. This is a stemmed hemispherical implant developed by Ascension Orthopedics (Integra Life Sciences, Austin, TX) that articulates with a hemispherical socket reamed into the distal surface of the trapezium. They implanted 54 PyC hemi-arthroplasties for arthritic joints. They reported variable results with only 80% survival at 22 months and 15 patients undergoing revision surgery during this period mainly because of subluxation. This was felt to be largely due to the trapezial cup depth being too shallow, possibly representing a technical learning curve issue. Whilst most of the patients had overall improvements in grip strength, pain and satisfaction, the investigators concluded that although there was a high complication rate (with subluxation attributed to a shallow trapezial cup in cases performed early in the learning curve), this may be an acceptable option for treatment of trapezial-metacarpal arthritis because loosening and subsidence were not seen in this series.

In order to address some of the concerns in relation to the Pyrohemisphere, the concept was advanced with the development of the Ascension Nugrip prosthesis [59, 60]. The NuGrip prosthesis (Integra Life Sciences, Austin, TX, USA) is a stemmed non-anatomic hemi-arthroplasty design similar to the Pyrohemisphere with a more anatomic stem, to suit the particular intramedullary geometry of the 1st MCP, and the addition, between the stem and the hemisphere, of a collar to decrease subsidence and a neck to increase range of movement without impingement. The articulation is via a hemisphere, which sits in a bony cup reamed into the distal trapezium.

1.6.2.2 Dermal grafts

Dermal grafts can be cellular or acellular and are allogenic and therefore available for immediate use. Allergy to bovine collagen, limited shelf-life and infection can limit their use [26].

Acellular dermal matrix grafts include Integra, DermACELL and Alloderm. Their use has been reported in burns, deep wounds and reconstructive surgery of the head and neck, abdominal wall and breast [2,42]. Apligraf is a commercially available bilayered cellular skin graft and is indicated for diabetic foot ulcers and venous ulcers that have not responded to conventional treatment [2]. It contains a lower dermal layer of bovine type I collagen and human fibroblasts and an upper dermal layer of human keratinocytes. It does not contain skin adnexal structures.

3.3.2 In vivo wound healing assays

Dermal TE using PU scaffolds/membranes requires the precise reconstitution of the skin bilayer. In an ovine full thickness wound model, which tested a PU (biodegradable temporizing matrix; BTM-2) [94], the Integra™ dermal regeneration template was compared to BTM-2. It was found that by 29 days all wound sites had healed comparably [94].

Hafeman et al. recently compared two PEUs prepared from LTI versus HDIt for use in skin TE, looking at the in vivo degradation of the two PEUs in a full excision model [58]. Both PUs showed limited inflammation; however, the LTI scaffold degraded significantly faster than the HDIt scaffold at 28 days, suggesting that it may be better for skin TE [58] as this rate is aligned with the desired design specifications.

7.7.5 Samples

Five serum samples were received from the Medisch Spectrum Twente Hospital Group, Enschede, The Netherlands. The samples were obtained from venipunctures of patients undergoing lithium therapy. The lithium concentrations were first determined in the hospital with an ISE (Cobas Integra 800, Roche, Basel, Switzerland). The lithium level was in the range of 0.49–0.90 mmol/L for all samples. The samples were subsequently analyzed by microchip CE on the same day. Additional samples were prepared as follows: whole blood was directly drawn into a sample collector after performing a finger stick on healthy volunteers, using disposable 21 gage lancets with a puncture depth of 1.8 mm (Haemolance, HaeMedic AB, Munka Ljungby, Sweden). These samples did not contain any lithium, and therefore a second sample was collected in a sample vial by pipetting from the finger stick of the healthy volunteer, and spiked with 2 mmol/L lithium. Finally, a heparinized plasma sample was kindly provided by the Medisch Spectrum Twente Hospital Group from a patient on lithium therapy. This sample contained a lithium concentration of 0.62 mmol/L, as determined by the hospital.