FORM OF SENIOR SUBORDINATED SECURED PROMISSORY NOTE

Exhibit 4.1

THIS NOTE HAS NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933,

AS AMENDED, OR THE SECURITIES LAWS OF ANY STATE, AND MAY NOT BE

SOLD, PLEDGED, OR OTHERWISE TRANSFERRED IN THE ABSENCE OF

REGISTRATION THEREUNDER OR AN EXEMPTION THEREFROM.

FORM OF SENIOR SUBORDINATED SECURED PROMISSORY NOTE

FOR VALUE RECEIVED, CARDIUM THERAPEUTICS, INC. , INNERCOOL THERAPIES, INC. AND TISSUE REPAIR COMPANY , each Delaware corporations (individually a “Borrower and collectively, the “Borrowers”), jointly and severally promise to pay to the order of ________________________, or its registered assigns (“Holder”), the principal sum of ___________________ dollars ($__________) with interest on the outstanding principal amount at a rate of twelve percent (12%) per annum (computed on the basis of actual calendar days elapsed and a year of 365 days) or, if less, at the highest rate of interest then permitted under applicable law; provided , however, upon any nonpayment of any principal hereof, such unpaid amount shall bear interest from the date of nonpayment until such amount is paid in full at eighteen percent (18%) per annum (computed on the basis of actual calendar days elapsed and a year of 365 days) or, if less, at the highest rate permitted by applicable law (the “Default Rate”). Interest shall commence with the date hereof and shall continue on the outstanding principal of this Promissory Note (this “Note”) until paid in accordance with the provisions hereof.

1. Definitions . For purposes of this Note, the following terms shall have the following meanings (capitalized terms used herein but not otherwise defined shall have the meanings provided therefor in the Agreement (as defined below)):

“ Affiliate ” shall mean with respect to any Person, any other Person (i) which directly or indirectly through one or more intermediaries Controls, or is Controlled by, or is under common Control with, such first Person, (ii) which beneficially owns or holds 10% or more of any class of the voting stock of such first Person, or (iii) whereby 10% or more of the voting stock (or in the case of a Person which is not a corporation, 10% or more of the equity interest) of such other Person is beneficially owned or held by such first Person or by a Subsidiary of such first Person.

“ Business Day ” means any day which is not a Saturday or Sunday or a legal holiday on which banks are authorized or required to be closed in San Diego, California.

“ Collateral ” means the property described in the Collateral Documents, and all other property now existing or hereafter acquired which may at any time be or become subject to a Lien in favor of the Investors (or any Collateral Agent on their behalf) pursuant to the Collateral Documents or otherwise, securing the payment and performance of the Obligations.

“ Common Stock ” means the common stock of the Company, par value $0.0001 per share, and any other class of securities into which such securities may hereafter be reclassified or changed into.

1

“ Common Stock Equivalents ” means any securities of the Company or the Subsidiaries which would entitle the holder thereof to acquire at any time Common Stock, including, without limitation, any debt, preferred stock, rights, options, warrants or other instrument that is at any time convertible into or exercisable or exchangeable for, or otherwise entitles the holder thereof to receive, Common Stock.

“ Change of Control ” means any “person” or “group” (as such terms are used in Sections 13(d) and 14(d) of the Exchange Act, but excluding any employee benefit plan of such person or its subsidiaries, and any person or entity acting in its capacity as trustee, agent or other fiduciary or administrator of any such plan) becomes the “beneficial owner” (as defined in Rules 13d-3 and 13d-5 under the Exchange Act, except that a person or group shall be deemed to have “beneficial ownership” of all securities that such person or group has the right to acquire, whether such right is exercisable immediately or only after the passage of time (such right, an “ option right ”)), directly or indirectly, of 50% or more of the equity securities of the Company entitled to vote for members of the board of directors or equivalent governing body of the Company on a fully-diluted basis.

“ Exchange Act ” means the Securities Exchange Act of 1934.

“ GAAP ” means generally accepted principles of good accounting practice in the United States, consistently applied.

“ Lien ” shall mean any security interest, mortgage, pledge, hypothecation, assignment, deposit arrangement, encumbrance, lien (statutory or other), claim or other priority or preferential arrangement of any kind or nature whatsoever (other than a financing statement filed by a lessor in respect of an operating lease not intended as security).

“ Material Adverse Effect ” shall mean an event, matter, condition or circumstance which (i) has or would reasonably be expected to have a material adverse effect on the business, properties, results of operations or financial condition of the Borrowers on a consolidated basis; (ii) would materially impair the ability of the Borrowers or any other Person to perform or observe its obligations under or in respect of the Transaction Documents; or (iii) affects the legality, validity, binding effect or enforceability of any of the Transaction Documents or the perfection or priority of any Lien granted to the Investors (or any Collateral Agent) under any of the Collateral Documents.

“ Obligations ” shall mean all obligations of the Company to Holder howsoever created, arising or evidenced, whether direct or indirect, joint or several, absolute or contingent, or now or hereafter existing, or due or to become due, which arise out of or in connection with this Note including, without limitation, all costs and expenses incurred by Holder in connection with the enforcement of this Note or the Collateral Documents.

“ Organic Document ” means, relative to any Person, its articles or certificate of incorporation, or certificate of limited partnership or formation, its bylaws, partnership or operating agreement or other organizational documents, and all stockholders agreements, voting trusts and similar arrangements applicable to any of its capital stock, partnership interests or other ownership interests.

“ Qualified Asset Monetization ” shall mean the sale, license or other transfer or disposition of assets of the Company or any Subsidiary which results in the Company or any Subsidiary receiving gross proceeds of at least $10,000,000 at the time of closing of such transaction.

2

“ Qualified Financing ” shall mean any equity or debt financing transaction consummated by the Company or any Subsidiary which results in the Company or any Subsidiary receiving gross proceeds of at least $10,000,000 at the time of closing of such transaction.

“ Qualified Stock Sale ” shall mean the sale of capital stock of any Subsidiary which results in the receipt of gross proceeds of at least $10,000,000 at the time of closing of such transaction.

“ Person ” shall mean an individual, a partnership, a corporation, a limited liability company, an association, a joint stock company, a trust, a joint venture, an unincorporated organization and a governmental entity or any department, agency or political subdivision thereof.

“ Requisite Holders ” mean holders of a majority of the aggregate principal amount of outstanding Notes as of a particular date.

“ Senior Indebtedness ” shall mean all principal of or the interest or premium, if any, on all secured indebtedness of Borrowers under the Company’s Senior Secured Promissory Notes dated November 5, 2008 and November 10, 2008 (the “Senior Notes”) issued pursuant to that certain Note and Warrant Purchase Agreement dated November 5, 2008, and any extensions, renewals or refinancings thereof.

“ Subsidiary ” shall mean, with respect to any Person (herein referred to as the “parent”), any corporation, limited liability company, partnership, association or other business entity (a) of which securities of other ownership interests representing more than 50% of the equity or more than 50% of the ordinary voting power or more than 50% of the general partnership interests are, at the time any determination is being made, owned, controlled or held by the parent, or (b) that is, at any time any determination is made, otherwise Controlled by, the parent or one or more Subsidiaries of the parent and one or more Subsidiaries of the parent.

2. Note and Warrant Purchase Agreement . This note (the “Note”) is issued pursuant to the terms of that certain Note and Warrant Purchase Agreement (the “Agreement”) dated as of February 27, 2009, by and among the Company and the investors set forth in the Schedule of Investors attached thereto as Exhibit A . This Note is one of a series of notes (the “Notes”) having like tenor and effect (except for variations necessary to express the name of the holder, the principal amount of each of the Notes and the date on which each Note is issued) issued or to be issued by the Company in accordance with the terms of the Agreement. The Notes shall rank equally without preference or priority of any kind over one another, and all payments on account of principal and interest with respect to any of the Notes shall be applied ratably and proportionately on the outstanding Notes on the basis of the principal amount of the outstanding indebtedness represented thereby.

3. Maturity . Unless sooner paid in accordance with the terms hereof, the entire unpaid principal amount and all unpaid accrued interest shall become fully due and payable on the earlier of (i) June 27, 2009, (ii) the closing of a Qualified Asset Monetization, Qualified Financing Transaction or Qualified Stock Sale or (iii) the acceleration of the maturity of this Note by the Holder upon the occurrence of an Event of Default (such earlier date, the “Maturity Date”).

3

4. Payments .

(a) Form of Payment . All payments made hereunder shall be in lawful money of the United States of America to Holder, at the address specified in the Agreement, or at such other address as may be specified from time to time by Holder in a written notice delivered to the Company. Except as otherwise provided in the Collateral Documents, all payments shall be applied first to accrued interest, and thereafter to principal.

(b) Interest Payments . The Company shall pay to Holder accrued interest and unpaid interest on the Maturity Date or on the prepayment date as applicable. Interest at the rate first set forth above shall accrue on any interest which has not been paid on the date on which it is payable until such time as payment therefor is actually delivered to Holder.

(c) Origination Fee . The Company shall pay to Holder an origination fee (“Origination Fee”) equal to the original principal amount of this Note multiplied by 0.05. The Origination Fee shall be payable at Maturity.

(d) Prepayment . The Company may at any time, without the consent of the Holder, prepay any amounts owing under this Note in whole or in part without penalty.

(e) Collateral Documents . The Company’s obligations hereunder shall be secured pursuant to the Collateral Documents.

5. Default .

(a) Events of Default . For purposes of this Note, any of the following events which shall occur shall