# TKAine: System of Bioresorbable Implants for Sustained Postsurgical Analgesia Following TKA

> **NIH NIH R43** · ALLAY THERAPEUTICS INC · 2020 · $251,113

## Abstract

Total knee replacement arthroplasty (TKA) is a $3.3 billion U.S. market with annual number of surgeries
projected at 3.48 million by 2030 with transitioning shares from in-hospital to ambulatory surgical centers. The
procedure can cause significant, immediate and prolonged post-operative pain that undermines rehabilitation
and adversely affect outcomes. Pain following TKA is currently managed by a multi-modal strategy of oral pain
management and short-term loco-regional therapies. These include local anesthetic blocks of peripheral nerves
via single shot injection or continuous infusion ambulatory pain pump, requiring anesthesiologist administration
using ultrasound guidance. As an alternative to nerve blocks, surgeon administered local infiltration of
bupivacaine or cocktails of other local anesthetics has increased in popularity, but variability in operator
administration has given rise to variability in pain control. To facilitate compliance with physical therapy and
preempt breakthrough pain, when local anesthetics wear off, opioids are commonly prescribed. However,
prevention of opioid dependency and addiction has become an urgent public health emergency.
 The TKAine system may solve these challenges by providing sustained post-operative analgesia for a 14-
day duration with bupivacaine HCl monohydrate as the active pharmaceutical ingredient. Bupivacaine (BUP), a
sodium channel blocker, is the active, non-opioid, pharmaceutical ingredient in US-approved MARCAINE and
EXPAREL. Each TKAine system implant consists of a compressed film comprising bupivacaine, a biocompatible
water-soluble agent, and PLGA bioresorbable polymeric matrix. The implant is fabricated with a drug-containing
core layer sandwiched between non-drug-containing bioresorbable polymer layers. This proprietary construction
enables a high density loading of drug wherein the drug represents nearly two-thirds the total weight. The TKAine
system, which consists of multiple sterile drug delivery implants equaling a 14-day dose of up to 2 grams of BUP,
is implanted at the conclusion of TKA utilizing a simple, reliable, straightforward, sterile technique by the
orthopedic surgeon. The biodegradable polymer then fully erodes in < 12 weeks leaving no foreign body present.
 This Phase I will determine dosing levels to achieve a targeted efficacy concentration for 14 days. A major
technical challenge is to determine tissue concentration level that corresponds to therapeutic benefit. More
specifically, first we will complete a survey of expert pain management clinicians to compile data on optimal
dosing levels of BUP (delivered as MARCAINE, EXPAREL, other analgesic cocktails, and/or OnQ* Pump) to
achieve 12 to 72 hours of therapeutic benefit for current treatments. Response matrix summary analytics will
then provide a dosing strategy for an in vivo sheep study. Sheep will be injected with those targeted doses and
tissue samples analyzed at different time intervals to determine the resultin...

## Key facts

- **NIH application ID:** 10134612
- **Project number:** 1R43AR078738-01
- **Recipient organization:** ALLAY THERAPEUTICS INC
- **Principal Investigator:** Patrick Ruane
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $251,113
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134612

## Citation

> US National Institutes of Health, RePORTER application 10134612, TKAine: System of Bioresorbable Implants for Sustained Postsurgical Analgesia Following TKA (1R43AR078738-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10134612. Licensed CC0.

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