C O M M U N I C A T I O N S
2)-treated eyes were 24 ( 8 and 54 ( 16 mmHg, respectively.
The leaking pressure for the eyes repaired with hydrogel sealant
(N ) 8) was 184 ( 79 mmHg. Normal intraocular pressure is
between 12 and 16 mmHg. The incision is not sealed using only
the dendron or PEG-DA hydrogel precursors. The hydrogel sealant
secures the clear corneal incision and withstands higher pressures
and stress placed on a wound than conventional suture or self-
sealed treated wounds. The procedure with the hydrogel sealant is
facile and requires less surgical time than conventional suturing
(4-6 times) and does not inflict additional tissue trauma. The cross-
linked hydrogel sealant is transparent, adhesive, elastic, hydrophilic,
and acts as a physical barrier to the ocular surface.
In summary, a new in situ polymerizing hydrogel is reported
that gels within a few minutes from the multiple thiazolidine
linkages formed between the cysteine residues of the dendron and
the poly(ethylene glycol) macromers. The use of a hydrogel sealant
as opposed to nylon sutures or the self-seal approach in cataract
surgeries may provide a facile method to safely and effectively
seal the incision while reducing potential complications. These
results further support the synthesis and evaluation of dendritic
macromolecules for medical applications, where a high level of
molecular control can be used to vary and optimize chemical,
physical, and mechanical properties.
Figure 2. (left) Photograph of a synthesized 3‚5 hydrogel and (right)
photograph of a 3‚5 hydrogel sealant-repaired 3-mm clear corneal incision
(incision is between the two purple dots and gel is within the blue border).
The larger dendron 4 was prepared in a similar manner except that
an additional Lys coupling reaction was performed. In this reaction,
the BocLys(Boc)OH was used instead of ZLys(Z)OH to increase
the solubility of the larger Lys-dendron intermediate in organic
solvents. Finally, the Boc and iso-protecting groups of cysteine were
removed using TFA and 1 N HCl in MeOH, respectively, to afford
dendron 4. The dendrons were fully characterized by NMR, FAB-
MS, and elemental analysis (see Supporting Information).
To prepare the hydrogels, dendron 3 or 4 was reacted with poly-
(ethylene glycol dialdehyde) of 3400 Mw (5, PEG-DA) in HEPES
buffer at pH ) 7.4 (Figure 1). The ratio of cysteine to aldehyde
was 1:1, and the total concentration of polymer in solution was
either 30 or 50% w/w. A hydophilic gel formed spontaneously
within three minutes upon mixing the two aqueous solutions at
either concentration (Figures 1 and 2). The gels exhibited vis-
coelastic properties. Cylindrical hydrogel samples of 8-mm diameter
and 2-mm thickness were prepared and analyzed after setting at
25 °C for 24 h. The mechanical properties were measured at a
frequency of 1 Hz. The complex modulus (G*) for the 30% w/w
hydrogels prepared from 3 or 4 and 5 was 3.8 × 103 and 1.0 ×
104, respectively. The increase in modulus is consistent with the
increase in cross-linking density present in the 4‚5 hydrogel.20 The
hydrogels were transparent, and the 3‚5 hydrogel had a refractive
index of 1.397 at 37 °C, similar to the human cornea (n37 ) 1.376).
Cataract removal is the most commonly performed ophthalmic
surgical procedure, with 11 million/year performed worldwide, and
this number is expected to increase with the aging demographics.
A cataract is the clouding of the lens that decreases vision. Today,
surgeons break up and remove the cataract using ultrasound energy
and implant a synthetic intraocular lens, all through an incision in
the cornea. At the conclusion of the procedure, this corneal incision
is either left alone to “self-seal” or closed with nylon sutures.
Suturing inflicts trauma to the tissue and has risks such as
increasing inflammation and vascularization.21-23 Moreover, sutures
need to be removed post-operatively. The “self-seal” approach also
has its drawbacks, including leakage and increased risks of infection
(i.e., endophthalmitis).24 To determine whether this hydrogel sealant
would secure a corneal incision, we performed a series of
experiments on enucleated eyes to evaluate the leaking pressures
of self-sealed, suture, or hydrogel sealant-repaired incisions.
A 3-mm clear corneal linear incision was made in an enucleated
eye. This wound was either left to self-seal or closed using one
interrupted 10-0 nylon suture or the hydrogel sealant. For the
hydrogel sealant, dendron 3 and PEG-DA, 5, were mixed quickly
at room temperature, and then ∼5 µL of the hydrogel sealant was
applied to the incision (Figure 2). Within 5 min of repairing the
incision, saline was injected in the anterior chamber via a syringe
pump until the repaired incision leaked. In this in vitro study, the
mean leaking pressure for the self-seal (N ) 7) and suture (N )
Acknowledgment. This work was supported by the NIH and the
Johnson and Johnson Focused Giving Program. We thank the North
Carolina Eye Bank. M.W.G. also thanks the Dreyfus Foundation for a
Camille Dreyfus Teacher-Scholar Award and the Alfred P. Sloan
Foundation for a Research Fellowship.
Supporting Information Available: Experimental details. This
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