BIOVASCULAR SCAFFOLDS – CURRENT STATUS

Dr. ANSHUL KUMAR GUPTA

Seminar

11.06.2015

OVERVIEW

History & evolution of BVS

Physiology of BVS

Advantages

Types of BVS

Clinical trials

Future perspectives

• First revolution- balloon angioplasty

• Invention of balloon angioplasty as a percutaneous treatment for obstructive coronary disease by Andreas Gruntzig in 1977.

Plain Old Balloon Angioplasty (POBA)

Dissections – Focal to threatened dissectionAcute recoilChronic constrictive remodeling

• Second revolution – BMS

• The advent of BMS and the landmark Belgian-Netherlands Stent Study (BENESTENT) and Stent Restenosis Study (STRESS) trials have established BMS as the second revolution in interventional cardiology.

• A solution to acute vessel occlusion by– sealing the dissection flaps – preventing recoil – making emergency bypass surgery a rare occurrence.

– Serruys et al.A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease: Benestent Study Group. N Engl J Med. 1994;331:489–495.

Plain Old Balloon

Angioplasty(POBA)

Bare Metal Stent(BMS)

• Third revolution - DES

• The first 45 patients implanted with the sirolimus eluting Bx velocity stent (Cordis, Johnson & Johnson) were found to have negligible neointimal hyperplasia at follow-up.

• This was confirmed in the randomized comparison of sirolimus-eluting stent with a standard stent for coronary revascularization (RAVEL) study.

– Morice MC, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med. 2002.

• Disadvantages• Increased risk of late and very late ST.• late ST rates of 0.53%/y, with a continued increase to 3% over 4

years. – Late thrombosis in DES after discontinuation of

antiplatelet therapy. Lancet. 2004

• In the (ARTS II) trial, the rate of combined definite, probable, and possible ST was as high as 9.4% at 5 years, accounting for 32% of MACE.

– J Am Coll Cardiol. 2009–

• Postmortem specimens of DES revealed significant numbers of uncovered struts with persistent inflammation around the stent struts.

• Vasomotion testing demonstrated vasoconstriction to Ach. – Vascular responses to drug eluting stents: importance of

delayed healing. Arterioscler Thromb Vasc Biol. 2007

• Fully Bioresorbable Scaffold: The Fourth Revolution in Interventional Cardiology?

Why Bioabsorbable stents??

Potentially: no late stent thrombosis and no need for prolonged antiplatelet therapy

MRI / CT compatibility (allows non-invasive follow ups)

No “Full metal jacket” makes later treatments of the same segment easier (e.g., surgical bypass)

Leaves no stent behind long-term (no chronic inflammation, no long-term impact on local vasomotion)

Provides stent scaffolding and radial strength properties as long as needed to ensure an open lumen – same as permanent stent

Potential advantages of BRS

• On Premise that scaffolding & drug are only required on a temporary basis following coronary interventions.

• Several studies support this concept and indicate that there is no incremental clinical benefit of a permanent implant over time.

• Use of Absorbable scaffold eliminates the presence of a mechanical restraint and offers potential of restoring natural vessel reactivity.

– Incidence of restenosis after successful coronary angioplasty: a time-related phenomenon. A quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months. Circulation, 1988.

Vascular Reparative therapy

While stent performance is characterized by a single phase (Revascularization), the performance of Absorb is governed by three distinct phases: Revascularization Restoration Resorption.

Together, these phases of Absorb performance deliver VRT

What is Required of a Fully Bioresorbable Scaffold to Fulfill the Desire for ‘Vascular

Restoration Therapy’?

Revascularization Restoration Resorption

0 to 3 months 3 to ~6-9 months + ~9 months +

Performance should mimic that of a standard DES

Transition from scaffolding to discontinuous structure

Implant is discontinuous and inert

• Good deliverability

• Minimum of acute recoil

• High acute radial strength

• Controlled delivery of drug to abluminal tissue

• Excellent conformability

• Gradually lose radial strength

• Struts must be incorporated into the vessel wall (strut coverage)

• Become structurally discontinuous

• Allow the vessel to respond naturally to physiological stimuli

• Resorb in a benign fashion

What is Required of a Fully Bioresorbable Scaffold to Fulfill the Desire for ‘Vascular Restoration Therapy’?

1 3 6 2 Yrs

Full Mass Loss & Bioresorption

Mos

Platelet Deposition

Leukocyte Recruitment

SMC Proliferation and Migration

Matrix Deposition

Re-endothelialization

Vascular Function

Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.

Revascularization Restoration Resorption

Everolimus ElutionMass Loss

Support

Oberhauser JP, et al., EuroIntervention Suppl. 2009; 5: F15-F22.

• Vessel Remodeling • Through the use of the imaging modality

intravascular ultrasound (IVUS), data from the ABSORB Cohort B trial, reveals an increase in lumen area between 6 months and 2 years.

• As Absorb resorbs, the vessel segment becomes unconstrained and there is the potential for lumen gain.

• Vasomotion • As Absorb resorbs, the treated vessel segment is

able to react to changes in blood flow and physiological stimuli that may occur with exercise or certain drugs.

• By no longer supporting or caging the vessel, there is the potential for allowing the vessel to respond naturally to physiological stimuli, which could provide unique benefits.

MECHANICAL CONDITIONING IN PRE-CLINICAL MODEL (PORCINE)

Tests were performed by and data are on file at Abbott Vascular.

Transmission Electron Microscopy (TEM) Smooth Muscle -Actin

Dense bodies

At 36 months, SMCs are well organized and have undergone transformation to a functional, contractile phenotype

Mechanical conditioning

Types of Bioabsorbable stents

Types of Bioabsorbable stents

First absorbable stent implanted in humans

Constructed from PLLA. Hydrolysis of bonds between

repeating lactide units produces lactic acid that enters the Krebs cycle

first-in-man prospective, nonrandomized trial that enrolled 50 pts

4yr follow-up of all pts revealed a low complication rate.

loss index (late loss/acute gain) was 0.48 mm, which was comparable to BMS

Tamai H, Igaki K, et al. Circulation 2000

IGAKI – TAMAI Bioabsorbable STENT

• Despite impressive initial results, failure of the stent to progress was related primarily to the use of heat to induce self-expansion.

• Concerns - could cause necrosis of the arterial wall, leading to excessive intimal hyperplasia or increased platelet adhesion, leading to ST.

• Biodegradable peripheral Igaki-Tamai stents PERSEUS study, the stent became available in Europe for peripheral use.

– Biamino G, Schmidt A, Scheinert D. Treatment of SFA lesions with PLLA biodegradable stents: results of the PERSEUS Study. J Endovasc Ther. 2005;12:5.

Igaki Tamai – 10 yr follow up (n=50)

Kaplan-Meier curves showing:-

(A)survival rates free of cardiac death(B) Death(C) major cardiac adverse events.

Cumulative rates of :-

target lesion revascularization (TLR)target vessel revascularization (TVR)

Circulation 2012.

Biotronik Absorbable Metal STENT (AMS)

• Prolonged mechanical stability, different Mg alloy with a higher collapse pressure and slower degradation time.

• Modified stent surface - strut thickness reduced

• Shape of the strut changed from rectangular to square (improving radial strength).

• Prolonged scaffolding and stent integrity, improved radial strength, and reduced neointimal proliferation in animal models.

AMS – 2 STENT

• The AMS-3 stent (drug-eluting AMS) is designed to reduce neointimal hyperplasia by incorporating a bioresorbable matrix for controlled release of an antiproliferative drug onto the AMS-2 stent.

• Research is currently focused on establishing the ideal drug kinetics; initial animal trials have demonstrated a sustained antiproliferative effect at 1 month.

AMS - 3 STENT

The degradation of Mg produces an electronegative charge that results in the stent being hypothrombogenic.

PROGRESS AMS trial: Lancet. 2007;369:1869 –1875.

PROGRESS AMS was a non randomized, prospective study in 63 pts.

Stent was completely absorbed within 2 mths, radial support was lost much earlier there was an insufficient radial strength to counter the early negative remodeling forces after PCI.

In addition, it did not release an antiproliferative drug to counter the intimal hyperplastic response to stenting.

High restenosis rate at 4 months of almost 50% and target vessel revascularization at 1 year was 45%. MACE rate 26.7% at one yr.

MagnesiumBioabsorbable

STENTs

Stent: Bioabsorbable

Magnesium AlloyDiscrete Drug

Delivery Reservoirs

Drug:Pimecrolimus

Carrier:

Bioresorbable Matrix

Modifications

Biotronik DREAMS (Pimecrolimus – Eluting stent system)

BIOSOLVE II TRIAL is ongoing with DREAMS 2nd gen drug eluting AMS.

REVA Medical – Stent features

RESORB Study

RESORB Study

(REVA Endovascular Study of a Bioresorbable Coronary Stent) trial enrolled 30 pts at multiple sites in Germany and Brazil

Non-randomized study

Endpoints• Primary – 30 days MACE• Secondary – 6 mths QCA & IVUS derived parameters for

restenosis.

Clinical follow up• At discharge, 2 wks, 1, 6, 12, 24, 36, 48, 60 months.• Subset of pts will be returning for long term angiographic

follow up.

6 mths follow up showed absence of any significant vessel recoil.

Unfortunately higher-than-anticipated rate of TLR (66.7%) were seen between 4 and 6 months.

The degree of neointimal hyperplasia was similar to that of a BMS

Redesigning of the stent ensued, resulting in the second-generation ReZolve stent.

• More robust polymer, a spiral slide-and-lock mechanism to improve clinical performance, and a coating of sirolimus (80% is eluted by 30 days and 95% by 90 days.)

• The RESTORE Trial evaluating the safety and performance of the 1st-generation ReZolve scaffold in 26 pts.

• One yr follow up showed late lumen loss comparable to that of DES.

• The ReZolve2 scaffold, a lower profile and sheathless version of the original ReZolve scaffold evaluated clinically in the RESTORE II TriaL (started in 2013)

ReZolve stent

Poly (Anhydride ester) Salicylic acid : the IDEAL stent

• IDEAL stent is radio-opaque and salicylate acts as anti- inflammatory agent.

• Whisper trial, a stent with strut thickness of 200 µm and a crossing profile of 2.0 mm with a stent-to-artery coverage of 65% was implanted in 8 patients.

• Because of higher-than-expected intimal hyperplasia, a subsequent design iteration will have thinner struts, a higher dose of sirolimus, and a lower percent wall coverage.

Crossing profile of 1.4 mm with circumferential hoops of PLLA.

The struts are 150 µm thick and are either directly joined or linked by straight bridges.

Both ends of the stent have 2 adjacent radiopaque platinum markers. radial strength = BMS.

The backbone of the BVS device is made of semicrystalline polymer called PLLA.

Coating of poly D,L-lactide acid (PDLLA).

Coating contains and controls the release of everolimus.

Everolimus-Eluting PLLA Stent: BVS Scaffold

BIORESORBABLE POLYMER

Everolimus/PDLLA Matrix Coating

• Thin coating layer• Amorphous (non-

crystalline)• 1:1 ratio of

Everolimus/PLA matrix• Conformal Coating, 2-4

m thick• Controlled drug release

PLLA Scaffold• Highly crystalline• Provides device

integrity• Processed for increased

radial strength

Polymer backbone

Drug/polymer matrix

Absorb Design Elements

BVS : clinical evidence

Lancet 2008; 371: 899–907

ABSORB cohort A study

Prospective, open-labeled, non-randomized, multi-center trial.

First in Man ABSORB stent

First clinical evaluation of the safety and performance of the BVS Cohort A device. (n=30)

Among 29 patients, the 5-year MACE rate was low at 3.4%, due to only one ischemic MACE event (non-Q wave MI.) that was reported within the first 6 months of the trial.

There were no incidences of (ID-TLR)

No incidences of scaffold thrombosis or cardiac death out to 5 years

ABSORB cohort A study

• N = 30; 6 sites (Europe, New Zealand)

• Clinical follow-up schedule:– 30 days, 6 months, 12 months, annually to 5 years

• Imaging schedule:

QCA, IVUS, OCT, IVUS VH Baseline6 18 24

MonthsMonthsMonths

MSCT(optional)

ABSORB cohort A study

Procedural success was 100% (30/30 pts)

Device success 94% (29/31 attempts)

At 1 year, MACE rate 3·3% (one pt having a non-Q wave MI and no TLR.

No late stent thromboses.

At 6mths, angiographic in-stent late loss was 0·44 (0·35) mm and was mainly due to a mild reduction of the stent area (–11·8%) as measured by IVUS.

ABSORB cohort A study – 1yr Results

Lancet 2009; 373: 897–910

ABSORB cohort A study – 2 years follow up

Serial assessment with OCT

At 2 years:-

Stent was bioabsorbed

Vasomotion restored

Restenosis prevented

Clinically safe, freedom from late thrombosis

Late luminal enlargement due to plaque reduction without vessel remodelling.

ABSORB cohort A study – 2 years results

HPE in a preclinical porcine study

J Am Coll Cardiol Intv 2013;6:999–1009

ABSORB cohort A study – 5 years results

ABSORB cohort A – 5 year clinical results

J Am Coll Cardiol Intv 2013;6:999–1009

Cohort A

Cohort B

• More uniform strut distribution

• More even support of arterial wall

• Lower late scaffold area loss―Maintain radial strength for at least 3

months

• Storage at room temperature

• Improved device retention

• Unchanged:– Material, coating and backbone– Strut thickness– Drug release profile– Total degradation Time

• More uniform strut distribution

• More even support of arterial wall

• Lower late scaffold area loss―Maintain radial strength for at

least 3 months

• Storage at room temperature

• Unchanged:– Material, coating and

backbone– Strut thickness– Drug release profile– Total degradation Time

BVS Device optimization

J Am Coll Cardiol 2011;58:1578–88)

ABSORB Cohort B study

• ABSORB Cohort B trial had two subgroups (B1 and B2) for follow-up purposes as determined by protocol.

• 3-year follow-up data for Group B1 (n=45) was reported at the TCT 2012 meeting in Miami, Florida, USA

• Among 100 patients, there has been no reported scaffold thrombosis or cardiac death.

• 2-year ischemic driven MACE rate was 9.0%, due to 3 non-Q wave MIs and 6 ischemia driven TLR.

ABSORB B1&2 study results

No scaffold thrombosis

ABSORB Cohort B1 study results

No new MACE between 6 mths to 3 yrs.

Clinical Procedure Success 98%

ABSORB B Group 1 –MACE rate of 6.8% at 2 and 3 years (1 peri-procedural MI & 2 TLR)

No additional MACE between 1 yr and 3 yrs

No scaffold thrombosis event.

Clinical data very comparable to Xience-V data from SPIRIT I+II+III.

Conclusion Absorb B study

MACE rates in ABSORB cohort B vs XIENCE V (SPIRIT I+II+III Study)

The ABSORB EXTEND trial is a continuation in the assessment of the safety and performance of Absorb in a larger study.

The lesions are longer than in the ABSORB Cohort A and Cohort B trials.

Planned overlap of Absorb scaffolds during the procedure

ABSORB EXTEND is a prospective, single-arm, open-label clinical study in 1,000 subjects at 100 global sites.

Clinical follow-up for up to 3 years.

ABSORB EXTEND Study

MACE AT 6 Months

ID – TLR at 6 Months

Stent Thrombosis at 6 Months

Conclusions from 6 mths data

6 months follow up data showed:-

Low event rates including MACE (3.0%) and Stent thrombosis (0.6%)

MACE rate shown at 6 months were sustained with the first 250 pts enrolled through 12 mths follow up

Data from ABSORB EXTEND demonstrated the consistency in clinical outcomes between ABSORB EXTEND, ABSORB Cohort B and the SPIRIT pooled population.

ABSORB EXTEND/Cohort B MACE (Through 12 mths)

ABSORB EXTEND/SPIRIT MACE (Through 12 mths)

ABSORB EXTEND/SPIRIT ID-TLR (Through 12 mths)

ABSORB EXTEND/SPIRIT Stent thrombosis (Through 12 mths)

ABSORB EXTEND – Diabetic subgroup6 mths clinical outcomes (n = 500)

Follow up of 250 pts at 12 months showed:-

Results comparing ABSORB EXTEND and Cohort B patient demographics and lesion characteristics:

Over twice the percent of UA (35.2% in EXTEND vs 14.9% in Cohort B)

Higher percentage of diabetics (24.8% in EXTEND vs 16.8% in Cohort B)

Longer mean lesion length than in ABSORB Cohort B Planned overlapping treatment permitted (6.4% of pts)

Findings on the 12 mths outcomes in 250 pts:- Comparable MACE rates to ABSORD Cohort B and SPIRIT Pooled

population Lower rate of ID-TLR (2.0%) in EXTEND compared to Cohort B

and SPIRIT Pooled population.

ABSORB EXTEND – conclusion from 12mths data

ABSORB II is a randomized, active-controlled, single-blinded, multicenter clinical trial and will enroll approximately 501 subjects in 40 sites in Europe.

Aim: primary endpoints of vasomotion and change in lumen diameter.

Subjects were clinically followed at 30 days, 180 days, 1, 2, and 3 years post-procedure

Imaging studies included angiography, IVUS/IVUS-virtual histology, MSCT, all at 2 yrs and 3 yrs.

ABSORB II: European RCT

ABSORB II one year analysis was presented in TCT 2014 and published in Lancet September 2014 issue.

ABSORB II

Patient characteristics

Lesion characteristics

Summary

Device success rates were comparable (100% vs 99%)

Acute gain by angiography and IVUS was significantly lower in Absorb arm than Xience arm.

Difference in acute gain was not related to acute recoil measured immediately after device implantation (0.19 mm for both) but could be attributed to the difference in pressure and nominal size of the balloon used during post-dilation performed in similar proportions (~60%) in each arm.

Two definite scaffold thromboses were documented – one acutely within 24 hrs and second subacutely on day 2.

The rate of definite stent thrombosis was 0.6% in the Absorb arm and 0% in Xience arm (p=1.0)

At one year Device related composite end points DoCE (cardiac death, TV-MI, and TLR, Absorb: 4.8% vs Xience: 3.0%, p = 0.35) and patient related composite end points PoCE (all deaths, all MI and all revascularization, Absorb: 7.3% vs Xience: 9.1% p= 0.47) and their components were similar between the two arms.

The ABSORB (RCT) is designed to evaluate the clinical safety and efficacy of Absorb for US approval in comparison with the XIENCE family.

The ABSORB III is a prospective, randomized, active-control, single-blind, multi-center clinical trial that will register approximately 2,250 subjects in up to 220 sites in the US and outside the US.

Cohort of approx 2,000 pts will be used for approval of Absorb by the US - FDA.

ABSORB III: US RCT for US approval

The ABSORB IV trial is similar in design to ABSORB III, and designed to enroll approximately 2,500 to 3,000 patients with clinical follow-up out to 5 years.

Clinical data from both ABSORB III and IV will be pooled to enable a landmark analysis for 4,500 to 5,000 subjects to show superior safety and benefits of Absorb compared to XIENCE.

ABSORB IV: RCT for Landmark analysis

ABSORB Japan is a prospective, single-blind, multi-center randomized 2:1 trial of Absorb: XIENCE V involving up to 400 subjects in up to 35 Japanese sites to seek Japanese approval.

The patient eligibility criteria are similar to the ABSORB III study.

The primary endpoint is 1 year target lesion failure (TLF) showing non-inferiority to XIENCE, with each subject returning for at least one imaging follow-up involving one of the following modalities: angiography, IVUS, and/or OCT.

ABSORB Japan: RCT

ABSORB China is a prospective, single-blind, multi-center randomized 1:1 trial of Absorb: XIENCE V involving approximately 400 subjects in up to 25 Chinese sites.

The patient eligibility criteria are similar to ABSORB III.

The primary endpoint is 9 months angiographic endpoint of in-segment late loss, showing non-inferiority to XIENCE, for Chinese approval.

Patients will subsequently return only for clinical follow-up out to 5 years.

ABSORB China: RCT

• The ABSORB FIRST Registry is designed to evaluate the safety and clinical outcomes of Absorb in daily use in patients with de novo lesions in previously untreated vessels.

• Single arm, prospective, international post-market registry of patients with de novo lesions in previously untreated vessels treated with Absorb per IFU (on-label use).

• Enrolling min of 10,000 pts in approx 300 sites throughout multiple countries worldwide where Absorb has regulatory approval and is commercially available.

• One yr follow-up will be conducted on all pts. Annual follow-up visits will be conducted in subgroups of 1,000 patients each from 2 to 4 years.

ABSORB FIRST: International Post-Market Registry

N=100Cohort 1 – 46 pts with UACohort 2 – 38 pts with NSTEMICohort 3 – 16 pts with STEMI

POLAR ACS results

• First, the optimal duration of scaffolding with drug-elution should be further elucidated.

• In both AMS-1 magnesium stent and BVS 1.0 scaffolds, late scaffold shrinkage was one of major contributors to luminal loss.

• In a previous study with serial IVUS imaging after angioplasty or directional coronary atherectomy, some positive remodeling occurred early after the procedure up to 1 month, whereas the negative remodeling occurred at 1 to 6 months

Future Perspectives

This suggests that the need to prevent negative remodeling is necessary at least until 6 months.

This could be achieved by tuning the biodegradation speed in changing the molecular weight of the polymer and increasing its crystallinity, thereby prolonging the mechanical integrity of the scaffold.

2. BRS technologies without drug elution such as REVA and AMS-1 were associated with high TLR rates.

In AMS-1 trial, 45% of late luminal reduction was attributed to neointimal hyperplasia at 6 mths.

These results suggest that the elution of antiproliferative agents might be indispensable to make the BRS clinically applicable and efficient at medium term.

3. The clinical advantage of BRS technology over the currently available DES needs to be further investigated.

BVS and Mg stents showed the recovery of responsiveness of the treated vessel to vasoactive agents such as nitroglycerin.

Restoration of vasomotion can indirectly stand for the completeness of vessel healing; however, it is still unclear what the real clinical advantage of this phenomenon is.

4. A potential drawback of this new technology is strut fracture.

Unlike metallic stents, the polymeric devices have inherent limit of expansion and can break as a result of overdilatation.

In an anecdotal case from the ABSORB cohort A, a 3.0-mm scaffold was overexpanded with 3.5-mm balloon, which resulted in strut fracture as documented with OCT.

The clinical significance of such a case, evidenced only by OCT, needs to be further elucidated, but undoubtedly fracture should be avoided by respecting the nominal size of the scaffold.

5. Data transferability might be another issue from the regulatory perspective.

In conventional metallic stents, the essential component was platform, coating, and drug.

In BRS polymeric stents, even with the same PLLA and design, the speed of bioresorption can be different according to the manufacturing process of PLLA.

Molecular weight of the polymer can influence the degree of inflammation.

Absence of large RCTs

Experience in complex cases (bifurcation, ostial, CTO) is limited and in such cases IVUS should support BVS implantation.

High strut thickness may lead to vessel injury, nonlaminar flow, platelet deposition, and poor deliverability.

Calcification or tortuosity are technically challenging.

Regardless of lesion anatomy, pre-dilation is mandatory, direct stenting is not possible.

Predilatation makes the system prone for dissection and ischemia

Current limitations and challenges

Only limited scaffold sizes are currently available, and special facilities are needed for storage of some.

Due to these technical particularities, the total cost and duration of PCI with a BRS may be higher than with a conventional DES.

Duration of DAPT with BRS is unclear.

Current limitations of BVS contd…

Current BRS limitations will likely be resolved in the future.

Although their advantages already outnumber their disadvantages, large, randomized, controlled trials are still needed.

Although promising in certain conditions but more randomised trials and technology advance is required to implement them in a wider perspective.

Future perspectives

Conclusions

Bioabsorbable scaffold technology is still in infancy but developing at fast pace.

Preliminary trials have shown quite hopeful results

Larger randomized trials are ongoing and their results will dictate the future of this novel technology.

Although promising in certain conditions at present but more randomised trials and technology advance is required to implement them in a wider perspective.

THANK YOU …

THANK YOU …

“In 10 years, we may look back and laugh at the time when we used to leave behind little pieces of metal inpatients’ vessels,”

Dr. Ron Waksman MD, FACCAssociate director at Washington

HospitalCenter, Washington, D.C.

Characteristics of an ideal Bioabsorbable stent

Predictable degradation rate over a finite period of time

Should leave no residue

Degradation products should be biocompatible, non-toxic and non-inflammatory

Stent material should have high tensile strength to allow creation of low profile, balloon expandable stent

Material should have adequate radial strength and mechanical properties for vessel support

Non-thrombogenic should not shed emboli

Material should be easily processed and sterilizable

Acceptable shelf life

Ideal characteristics of bioabsorbable polymer

Linear degradation profile

Fast degradation rate (< 6months)

Compatibility with hydrophilic and hydrophobic drugs

Stable under different pH

Good film forming properties

Solubility in common solvents

No toxic metabolic end products